April 2015

Mal's Musings



GLOSSARY & NOTES





CENTROSOME, GOLGI, APOPTOSIS, IMMUNITY and OTHERS



Copyright © M A Traill, 2005, 2006, 2007, 2008, 2009, 2011, 2012, 2013, 2014, 2015





ALPHABETICAL



5051: A centrosomal protein identified by an antibody obtained from a scleroderma patient. The antigen seems very highly conserved, and is found in
the poles of spindles without centrioles



Å: Angström unit; = m x10-10; unit frequently used in electron microscopy; distances of atomic influence are often expressed in this unit



5A5: Anti-polysialated-neural cell adhesion molecule



A20: (a) B cell lymphoma cell line, widely used for MHC class II-restricted antigen presentation

(b) An ubiquitin-editing enzyme; can be induced in THP-1 cells by TNF & IL-1β; up-regulates Pam3CSK4; terminates TLR -induced immune responses



5A11 ANTIGEN: A member of the immunoglobulin superfamily of receptor proteins



A375: An human malignant melanoma cell line



A549: A non-small cell lung cancer cell line – resistant to TRAIL-induced apoptosis



A2058: An human malignant melanoma cell line



A2780: An ovarian cancer cell line



A23187: A Ca2+ ionophore; releases Ca2+ from the ER; induces apoptosis (or necroptosis)



aa: Amino acid (in a peptide)



AA: (a) Arachidonic acid; released from membrane phospholipids by Phospholipase A2; metabolites can influence synthesis of soluble angiogenic
factors and basement membrane components

(b) Amyloid protein A; the precursor has an heparan sulphate-binding motif

(c) Ascorbic acid (Vitamin C)



AAA: (a) ATPases associated with cellular activities. Usually domains in large molecules (eg dynein)

(b) Abdominal aortic aneurysm



α-ACTININ: Actin cross-linking protein. Regulator of Actin cytoskeletal organization



AACR: American Association of Cancer Research



7-AAD: 7-aminoactinomycin D. It is a fluorescent DNA stain and is used in flow cytometry assessments for apoptosis (& necroptosis)



α-ADAPTIN: The main structural antigen in Clathrin-coated pits



AAF: IFN-α activated factor. Translocates to nucleus and bind to IFN-γ-activated sequence elements (GAS)



AAH: Atypical adenomatous hyperplasia



AAK1: Adaptin-associated kinase 1; phosphorylates the μ2 subunit of AP-2



AAL: Aleuria aurantia lectin; binds to α-1,2-, α-1,3- and α-1,6-linked fucosyl residues



α-AMANITIN: A transcription inhibitor from Amanita phylloides. It inhibits RNA eukaryotic polymerases II & III (not I or bacterial); blocks p53-dependent transcription



AASK: African American Study of Kidney disease



AAV: Adeno-associated virus



Aβ: β-Amyloid; a proteolytic product from APP; 39-42 aa peptide that forms fibrils and may associate with apolipoprotein E, laminin,
acetylcholinesterase, α1-antichymotrypsin & heparan sulphate proteoglycan (with four classes present); causes NLRP3 inflammasome formation/activation and pro-IL-1β processing by caspase-1 and cathepsin B in microglia; See also C83, C99, sAPPα



A2B5: A neuroendocrine marker; marker for rodent OPCs



ABATACEPT: A mAb with use against RA & similar

ABB: Ankyrin-binding buffer



ABC: ATP-binding cassette; the largest transporter gene family, transporting a wide range of ions to molecules; involved in cystic fibrosis and multiple drug resistance. Operation against gradients involves energy from ATP, for which they have nucleotide-binding domains and hydrolysis sites, of which there are two of each per transporter. They are involved in the transport of HSP for secretion to the ER and the secretion of IL-1β. Glibenclamide is an ABC family inhibitor



ABC1: Transfers cholesterol and phospholipids to protein acceptors and seems essential for macrophages to accept apoptotic cells and is a promoter of
scrambling in target cells.



ABCB1: ATP-binding cassette family B1. (Aka MDR1 and P-gp)

ABCB6: ATP-binding cassette, transports coproporphyrin III from the cytoplasm to the mitochondria

ABCC1: ATP-binding cassette family C1. (Aka MRP1)



ABCG2: Gene for ABCG2; on chromosome 4q22, over 66 kb, with 16 exons and 15 introns



ABCG2: ATP-binding cassette family G2 (aka BRCP); monomer 72 kDa, dropping to ~60 kDa after removal of the glycan group, N-linked at Asn596. It is responsible for the cellular homeostasis of porphyrins and related compounds; 6 transmembrane domains and one ATP-binding cassette, existing in the plasma membrane as an homodimer bound by cysteine; of the 11 cysteine residues, 3 in the extracellular loop are crucial for dimerization/protein levels. Glycan bonding seems important in stabilizing the nascent proteins for the homodimer in the ER. It is normally expressed by the placenta, small bowel epithelium, liver canaliculi and ducts/lobules of the breast.  Levels may differ in ethnic groups due to single nucleotide polymorphisms, and may give rise to increased sensitivity to porphyrin-induced phototoxicity; the wild type Km for haematoporphyrin may be 17.8 μM. The basic unit of one amine bonded to one carbon of a heterocyclic ring seems crucial, with fused rings and other variations possible. It may be reduced in many cancer



ABCP: See ABCG2



18 α,β-GLYCYRRHETINIC ACID: A gap junction blocker



αBgtx: α-Bungarotoxin



ABI: Abl inter-actor; required for engulfment of apoptotic cells



ABIRATERONE: A 17α-hydroxylase inhibitor



ABL: A tyrosine kinase that regulates the actin cytoskeleton in multiple ways; when mis-expressed, can be associated with types of leukaemia/lymphoma
(CML); also bleomycin lung fibrosis and breast cancer. Over 70 interactive proteins have been identified, most poorly understood



ABORTIVE CLATHRIN COATS: The brief assembly of clathrin and AP-2 in smaller proportions than for the canonical pit/plaque and that lasts only ~20 s
before dissolution



ABP: AMPA-binding protein



ABSCOPAL: Relating to the secondary effects upon non-irradiated tissues from irradiation on another target tissue



ABT-263: An inhibitor of Bcl-2; in vitro, with reduced PMCA4 levels, cancer cells are sensitized for apoptosis; clinical trails for it in cancer therapy have started

ABT:-510: A small peptide from TSP-1

ABT-737: Similar to ABT-263; reported to sensitize tumours to chemotherapies



α-BUNGAROTOXIN: From Bungarus multicinctus; MW ~ 8 kDa; a neurotoxin that binds irreversibly to motor endplate acetylcholine receptors and
prevents the opening of some receptor-operated ion channels



AC: (a) Adenylate cyclase; synthesizes cyclic AMP

(b) Accessory cell(s)



AC3-1: Autocamtide-3-derived peptide inhibitor; less potent that AIP



Ac-AEVD-pNA: A specific Caspase-10 chromogenic substrate



ACAID: Anterior Chamber-associated Immune Deviation



ACAMP: Apoptotic cell-associated molecular pattern; may be important as antigens in autoimmune disease



Ac-DEVD-AFC: N-Acetyl-Asp-Glu-Val-Asp-7-amido-4-trifluoromethylcoumarin; peptide substrate inhibitor for the identification of Caspases

Ac-DEVD-AMC: N-Acetyl-Asp-Glu-Val-Asp-amido-4-methycoumarin; peptide substrate inhibitor for the identification of Caspases

Ac-DEVD-CHO: N-Acetyl-Asp-Glu-Val-Asp-al; peptide substrate inhibitor for the identification of effector Caspases; inhibitor of effector caspases

Ac-DEVD-pNA: N-Acetyl-Asp-Glu0-Val-Asp-nitroanilide; peptide substrate inhibitor for the identification of Caspases



ACE: Angiotensin converting enzyme; curcumin may augment inhibitors of ACE



ACETAL: Product of alcohols and carbonyl group of aldehyde (in the presence of anhydrous acid) eg:

                                     H                             H

                                      |                               |

                                R'-C=O + 2ROH ⇒  R'-C-OR + 2H2O

                                                                      |

                                                                     OR

            Hemiacetals have only one alcohol molecule added



ACF7: Actin cross-linking family 7 (also MACF1). A +TIP



α-CHLOROHYDRIN: An inhibitor of GAPDH; is converted to 3-chlorolactaldehyde, a structural analogue of glyceraldehyde-3-phosphate. It reduces
GAPDH activity particularly in the rat liver, minimally in muscle



AChR: Acetylcholine receptor; antibodies to this are found in ~90% of myasthenia gravis patients



ACID SPHYNGOMYELINASE: Involved in the GI syndrome following ionizing irradiation. Counteracted by bFGF. Seems to involve the endothelium



acidicFGF (aFGF): = FGF-1



ACID STORE (Ca2+): Thapsigardin-unresponsive, Bafilomycin-sensitive (V-ATPase pump) in apical granular region of granular cells in the pancreas,
also lysosomes and endosomes



ACIVICIN: A potent inhibitor of GGT



Ac-LEHD-AFC: A substrate for assessing Caspase-9 activity



ACM: Astrocyte-conditioned medium



ACONITASE: Enzyme that adds water to cis-aconitate in the TCA (Krebs) cycle



ACP: Acyl carrier protein



ACR1-3: Three genes in Saccharomyces cerevisiae involved in the reduction of Arsenate to Arsenite



ACRIDINE ORANGE: Fluorescent metachromatic dye for detecting nucleic acids, and which shows red fluorescence when in acidic lysosomes



ACROCENTRIC CHROMOSOMES (Homo sapiens): Chromosomes that have the centromere near to one end, such that one end is much longer than the other; of 10, 5 are conspicuous - chromosomes 13, 14, 15, 21 & 22; ~300 rDNA repeats are spread amongst 5 NORs, found on the short arms of the five acrocentric chromosomes; typically, NORs are active & coalesce to form 1 – 3 nucleoli; fusions between the short arms are Robertsonian translocations and occur in 1 in 1000 live births



ACRODYNIA: A variant of Mercury poisoning



ACROSOMAL REACTION: The breakdown of the anterior tip (acrosome) of the capacitated Spermatozoon upon contacting the zona pellucida. It
releases enzymes and is essential for penetration of the zona pellucida and subsequent fertilization



Acr2p: An arsenate reductase; an homodimer of 34 kDa, requiring Glutathione as a cofactor and glutaredoxin for reduction. A member of the family that
includes Cdc25a



ACSF: Artificial CSF



Act1: An adapter protein - a negative regulator of BAFF-mediated B cell survival.



Actb: Gene (mouse) for Actin, beta, cytoplasmic. Not a good reference gene



ACTIN: Is the most abundant protein in the cytoplasm of mammalian cells, being ~10-20% of the total cytoplasmic protein. It forms much of cytoskeleton. In 2 forms: G-actin, which is in solution, and F-actin, which is filamentous. Polymerization from G to S requires ATP. At certain concentration treadmilling occurs, where units dissociate from the - end and a similar number added to the + end. The + end of a filament can extend 5 times faster than the - end. Controlled by a number of factors: Actin-binding proteins, Thymosin β4 and Profilin. Iatrunculin A depolymerizes; CaMK IID may bind to G-actin (Ca2+ not necessary), but bundle when Ca2+ is applied. See Cytochalasin and Phalloidin. Phosphofructokinase, aldolase and GAPDH bind to separate regions of F-actin. The binding by GAPDH is electrostatic (region near residue 103); Aldolase, around residue 299 near the C-terminal; that by Phosphofructokinase is over a diffuse region. Binding of these can modify configuration/reactions. Actin may be able to conduct ionic waves, acting as electrical transmission lines (see also for Microtubules, although the details may be dissimilar); De novo actin assembly requires pH 7.2, & slight changes (pH increments of 0.3-0.4) can be dramatic



ACTININON: A metalloproteinase inhibitor



ACTINOMYCIN D: An general inhibitor of transcription.



ACTIVIN: A signal molecule in the TGF-β superfamily; behaves as a morphogen, responding to the highest stimulus level in the exposure. Recombinant Activin A binds to perlecan and agrin, but not to laminins, nidogens, collagen I & IV, fibronectin and nephronectin. The binding to perlecan in blocked by heparin suggesting that the binding is to the heparan sulphate chains. Its blood level can be measured, and Activin A appears related to tumour aggressiveness, with upregulation of E-cadherin. Inhibin A inhibits it. It appears in the keratinocytes and granulation tissue of wounds, (along with FGF7/KGF) and appears to enhance granulation tissue production



ACV: (a) Acyclovir

(b) Adenylate cyclase type V



ACYL: R− C − ; Able to form an ester with an alcohol R'− CH2 − OH : -

||                                     R' − CH2 − O − C − R

O                                                              ||

O



ACYLATION: An important feature drawing molecules to lipid rafts



α-CYANO-4-HYDROXYCINNAMATE: Blocks MCT1



ACZONIN: See Piccolo.



AD: (a) Alzheimer's Disease; a degenerative condition involving the older brain, with a build-up of β-Amyloid and foci of neurofibrillary tangles, marking the ghosts of degenerated neurons; IL-1β seems to be a key factor in the inflammatory response; there may be a relationship between single nucleotide variations in the NLRP1 gene (see Aβ)

(b) Absorbed dose



AdA: Adenophostin A; a fungal glyconucleotide metabolite interferes with the IP3R binding site, being bound more firmly & is more potent than IP3. It is
more stable & has many analogues. There is diminished effect and shorter
to when ATP is absent



ADALIMUMAB: Humanized recombinant mAB anti-TNF-α - for therapy; by sc injection



ADAM: A disintegrin-like and metalloproteinase; a family of proteases; disintegrin and metalloproteinase -  'sheddases' responsible for the release of a number of membrane-bound receptors. Cholesterol or lipid rafts may inhibit them. They shorten the extracellular length of receptors (to ~<30 aa), making them substrates for γ-Secretase

ADAM10: α-Secretase

ADAM17: TACE



ADAMTS: A disintegrin-like and metalloproteinase with thrombospondin motif



ADAP: (SLAP-130/Fyb) adhesion and degranulation-promoting adaptor protein



ADAPTIN: Subunits of AP

Medium μ2
Small σ2



ADAR: Adenosine deaminase that acts upon RNA; such editing within the CNS is a requirement for homeostasis



ADCC: Antibody-dependent cellular cytotoxicity; applied to NK cell degranulation and perforin-dependent target cell lysis, usually in response to a
CD16-mediated activation signal



ADDUCIN: Spectrin-skeleton associated protein, forming ternary structures with spectrin & actin; caps the fast growing ends of actin filaments and promotes the association of spectrin and actin filaments; has a basic MARCKS homology motif that binds PKC (RTPS-serine), Ca2+ and calmodulin with α, β and γ subunits as dimers and tetramers, the MARCKS domains binding actin; spectrin/actin activities are inhibited by Ca2+ & calmodulin & PKC. Rho-dependent phosphorylation seems important for cell motility. The role(s) of the globular head domain is/are unknown, but zinc may be involved. It is phosphorylated and inactivated by PKC



ADE: Antibody-dependent enhancement. Ability of incomplete or weak antibodies to assist binding of virus to a monocyte or dendritic cell and aid cell invasion/intracellular activation. (eg Dengue, Ross River Virus, influenza and HIV). ADE-viral cell entry suppresses LPS-induced antiviral STAT-1 and NF-κB complexes



ADENOPHOSTIN A: A fungal glyconucleotide metabolite; agonist of IP3R by binding at the latter's core domain binding site



ADEM: Acute disseminated encephalomyelitis



ADENOSINE: A purine nucleoside. May be involved in multi-organ failure by activating adenosine receptors, stimulating TNF-α and IL-12 and increasing
IL-10; decreasing Th1 and increasing Th2 responses



ADF: Actin depolymerizing factor; see Cofilin Family



ADH-1: A cyclic pentapeptide that is an extracellular cadherin-N antagonist



ADHERENS JUNCTION: See AJ



ADHESINS: Heparan-binding proteins



ADHR: Hypophosphataemic rickets; from activating mutations in the FGF23 gene between residues 176-9, preventing proteolytic cleavage of FGF23



ADIPOKINE: Cytokine produced by adipose tissue: eg TNFα, IL-6, Leptin and adiponectin



ADIPONECTIN: Secreted by adipocytes, a hormone with insulin-sensitizing effects; in serum it is as trimers, hexamers or higher MW oligomers. There
are corresponding receptors



ADLD: Adult-onset autosomal-dominant leukodystrophy; a severe, progressive and lethal neurological degenerative condition that affects white matter, in particular; it is caused by duplication of the LMNB1 gene which results in overproduction of lamin B1 transcripts and protein, and this is associated with a reduction in proteolipid protein, a major component of myelin sheaths



ADP: (a) Adenosine diphosphate; a phosphate carrier & donor/recipient

(b) Adult (rat) dentate gyrus-derived neural precurser cell(s). Proliferation of these progenitor cells may be modulated by dexamethasone
and Lithium, probably involving GSK-3β and the β-catenin/TCF pathway



ADP/ATP ANTIPORTER: Imports ATP into the ER; 56 kDa. Mechanism poorly understood



ADPKD: Autosomal dominant polycystic kidney disease; usually has increased TRPP2 probably a mechano-sensor in cilia



ADPR: ADP-ribose; a product of NAD &/or cADPR breakdown by glycohydrolases, including ectoenzymes CD38 & CD157 & mitochondrial NADase and the combined actions of PARPs & PARGs (when responding to DNA damage); stimulates TRPM2 in lysosomes



ADVERSE EVENT: Any unfavourable and/or unintended sign, symptom or disease:

Grade 1 Mild Adverse Event
Grade 2 Moderate
Grade 3 Severe
Grade 4 Life threatening or disabling
Grade 5 Death related to Adverse Event

Elaboration: http://ctep.cancer.gov/forms/CTCAEv3.pdf



ADVILLIN: A member of the gelsolin/vellin family of actin regulatory proteins; binds to the cytoplasmic tail of SREC



AE GENE FAMILY: Involved in intracellular pH control, being HCO3-/Cl- exchange

AE1 Chromosome 17 - (Anion exchanger 1; band 3): Major protein of the human RBC membrane; N-terminal, 43 kDa, cytoplasmic/binding; C-terminal
transmembrane is ion exchanger. ~Half of the N-terminal is α-helical and acidic; binds ankyrin; most middle section (transmembrane) is highly
conserved; the C-terminal region is short and acid

AE2 - (band 3-related protein)

AE3 - (brain ion exchanger)



AE: Adverse event(s)



AE1 & 2: Anion exchangers, (see SCL4A1 & 2)



AEC: Aortic endothelial cells (animal)



AECA: Anti-endothelial cell antibody



AE1: Erythrocyte anion exchanger



α-ENaC: α-Epithelial Sodium channel (renal tubules)



AEQUORIN: From jellyfish of Aequorea victoria/sp. A Calcium-binding bioluminescent photoprotein which is retained within the ER lumen and can be
used to measure very low concentrations of Ca
2+



AF6: See Afadin



AFADIN: Co-localizes with cytoplasmic domain of Nectin and α-catenin and binds to actin



AFC: (a) Auto-fluorescent cells; those in the mouse spleen are mostly macrophages expressing FcγRI

(b) 7-Amino-trifluoromethylcoumarin



AFM: Atomic force microscopy



α-FODRIN: α-II-Spectrin. See Fodrin



α-FP: α-Foetoprotein; made by the foetal mammalian liver, and is prominent in the circulation at that age; it is ~absent from the serum of the adult (without liver disease); can become evident in CH, LC & HCC but, at low levels cannot be specific; production involves FUT8

α-FP-L3 fraction; is fucosylated and more specific for HCC



AG73: An active peptide from the laminin α1 chain (see also EF1); it promotes cell attachment via syndecan binding. AG73 and EF1 act synergistically



αGalCer: α-Galactosylceramide. It was originally isolated from a marine sponge and is non-toxic. It binds avidly to CD1d and activates NKT cells. Whether to
be directed to TH1 or TH2 response seems to depend upon other signals - usually there is activation of immune responses, but occasionally suppression



AGE: Advanced glycation end-products



AGGRECAN: The most prominent proteoglycan of cartilage, of chondroitin and keratan sulphates



AGLYCONE: A molecule without an attached glycosyl (sugar) group



AGM: Aorta, gonad and mesonephros; refers to regions of lymphoid development - thought to be the sites of haematopoietic stem cells origination,
later moving to the liver and thence to the spleen and bone marrow



AGN: Broad-range hydroxymate inhibitor of MMP activity



AGO: Argonaute (named after a founding member in Arabidopsis thaliana); the largest Class of small, ~bilobes proteins, MW ~90 kDa, that associate with microRNAs, guiding their degradation &/or translational repression; eight members, with 1-4 closely related and widely co-expressed; Ago1-4 require microRNP as well; one lobe contain an N-terminal, conserved PAZ domain to bind the 3'-end of small RNAs; the second lobe contains a MID domain for binding the 5'-phosphate of the guide RNA and the RNA H endonuclease domain (known as the PIWI domain); Ago is often linked in reports with Piwi (Ago/Piwi)

Ago2: Argonaute 2 protein; has exclusive endonuclease activity



AGR129: Strain of mice deficient in type I & II IFN receptors and RAG gene 2



AGRIN: A basement membrane HSPG; muscle, myoneural, CNS, lung & kidney



AGOUTI SIGNALLING/RELATED PROTEINS: Involved with satiety



AgRP: Agouti-related protein



AHB: Acute hepatitis B



AHNAK: A giant nuclear protein (~700 kDa; 'giant' in Hebrew), a binding partner of the Heterotetramer Annexin22S100A102, mediated by the S100A10 at the C-terminal subunit of Ahnak, with the binding site on Annexin2 at the S100A10 segment; there being a 20 aa segment in Ahnak specific for the association. The complex attaches to membranes in a calcium-dependent fashion and in response to 'stress' (eg H2O2, scraping)



AhR: Aryl hydrocarbon receptor; activated by BP (& TCDD etc.) and translocates to the nucleus and associates with ARNT; highly conserved & knockout phenotypes have non-lethal defects, including failure to close the ductus arteriosus in mice after birth (as with AIP); prolonged activation, with nuclear translocation can induce ubiquitination (E3 ligase) & degradation of the receptor; E3 & AhR form an atypical complex, involved in proteasomal degradation of steroid hormone receptors; sustained activity may increase inflammation and tumour promotion; requires Hsp90 function for activity; activation augments the signalling pathways from CD95 and TRAIL receptors in keratinocytes, inducing apoptosis



AHSG: α2-HS-glycoprotein; a serum component that may be a marker for pre-eclampsia in pregnancy



AIA: Adjuvant induced arthritis; experimental arthritis induced in Lewis rats by immunization with Mycobacterium tuberculosis, said to involve the
bacterial Hsp65 and its epitopes, cross reacting with the mammalian counterpart Hsp60



AICD: Activation-induced cell death; can be induced (via CD95) in T cells by re-stimulating the TCR in activated T cells



AICP: Apoptosis induced compensatory proliferation



AID: Activation-induced cytosine deaminase; a key enzyme in CSR and affinity maturation; a B lymphocyte-specific DNA deaminase



AIDS: Acquired immune deficiency disease syndrome; late stage of an HIV infection, characterized by syncytium development.



AIF: Apoptosis inducing factor; a Janus flavoprotein oxydoreductase released from within the mitochondrial inter-membrane space (attached to the IMM) during apoptosis and necroptosis as the truncated form tAIF. It has no nuclease activity – it stimulates peripheral chromatin condensation and large-scale 50 kb DNA fragmentation; it may be released from mitochondria independently of cytochrome c (indicating limited damage to the OMM); in some situations Cathepsin D activates Bax, which is promoted by Bid; it is probably the earliest to appear ahead of Omi/HtrA2 and then Smac/DIABLO, Endo G and cytochrome c



AIH: Amphetamine-induced hyperlocomotion



AIM: Absent in melanoma; see ALR, TLR & PRR



AIOLOS: Transcription factor; see Ikaros



AIP: Autocamtide-2-related autoinhibitory peptide; KKALRRQEAVDAL; competes with substrates at the active site of CaMKII; a non-phosphorylatable analogue of autocamtide-2

AIP-II: A more potent analogue of AIP; KKKLRRQEAFDAY



AIP-1: Actin-interacting protein-1



AIR-1: An aurora-A kinase; required for centrosome maturation (C. elegans). In its absence, sperm centrioles attract a minimum of PCM and fail to attract
more; it being required for mitosis-specific recruitment of RCM



AIRE: Autoimmune regulator protein of the thymus; Chromosome 21q22.3. Those with mutants develop multiple autoimmune diseases. It is a transcription factor, probably acting as an activator of 200-1200 genes for selective ectopic antigen expression (in mice), primarily expressed in thymic medullary epithelial cells within the nucleus, monocytic DCs and weakly by thymocytes (slightly more in DP) in the thymus, granulocytes, but also by rare subsets in the lymph nodes, spleen, B cells, ovary and foetal liver. Mutations of the AIRE gene result in the APECED syndrome (=APS-1). It seems to be involved in tolerance induction for a restricted number of promiscuously expressed genes, by negative selection, appearing in the mouse embryo at E16, shortly after the rise in LTi, with RANKL signals. AIRE mTEC in the adult may require for maintenance RANKL signals by CD4+ αβTCRhi and CD40L . Because of the large number of genes that it influences in a selective way, other factors seem involved. The presence of thymocytes (Ag specific ?) seems to stimulate the production of AIRE by TEC. Expression is regulated by LTαβ heterotrimers on activated thymocytes signalling through LTβR on thymic medullary epithelial cells



AJ: Adherens junction; act as a physical ligand between cells and a regulator of cellular arrangement; supported by catenins, actin and other molecules, with connection to microtubules; forms circumferential belt (with actin) around epithelial cells, but more spotty on fibroblasts, and small puncta on neurons; maturation stimulates the formation of tight junctions in vertebrates. The link to actin seems to be via α-catenin and EPLIN, although formin & vinculin may be involved. Contact with microtubule plus ends is with CLIP-170 & dynein. The minus ends of microtubules may link with p120-catenin. This may involve PLEKHA7 (which may be specific for the ZA) and Nezha (which may be more general), Nezha binding the minus ends of the MT



AKA: Also known as



AKAP: A-kinase-anchoring protein



AKATA: Burkitt's lymphoma cell line, EBV+



A KINASE ANCHORING PROTEINS (AKAP450) = CG-NAP: A scaffolding protein that binds PKA. Dislodging it by a C-terminal fragment in HeLa
cells impairs cytokinesis and increases ploidy; Untransformed fibroblasts arrest in G1; Centriole duplication is disrupted.



AKR/N: Strain of mice particularly sensitive to the 2-cell block in embryogenesis



Akt: (PKB) A PKC-related serine/threonine protein kinase identified after inclusion in the Akt8 virus and traced to chromosome 14q32; activated by some growth factors by phosphorylation of Ser473 near the C terminal & Thr308 (both required for full activity); typically phosphorylated by PIP3 as P donor & PDK1. TNF can have it phosphorylated via GSK-3 by 5 min, but more fully by 30 min; in some cells it is constitutively phosphorylated & active: promotes glucose uptake and glycolysis, inhibits apoptosis by phosphorylating Bad, which interacts with 14-3-3 and dissociates from Bcl-XL. Also phosphorylates Ser21 of GSK-3α & Ser9 of GSK-3β, inactivating them, Caspase-9, ASK1 at Ser83 and forkhead transcription factor. Considered to be pro-cancer and a prognostic indicator for platinum treatment and survival in those with certain cancers. See PKB/Akt. BAFF triggers Akt phosphorylation in B cells; reduced phosphorylation involving Akt308 has been associated with hyperdopaminergic tone in mice. Akt seems to play an important part with GSK-3 in affective diseases and may influence the response to Lithium treatment; hyperaction modulates translation elongation



AKTI-17: A highly selective, allosteric Akt inhibitor



ALA: (a) δ-Aminolevulinic acid; it collects in tumours and, in some cells, converts to PpIX, which is fluorescent and can assist surgical identification
of tumour limits (Photodynamic diagnosis). Overload applied to cells induces detectable PpIX, making the cells photosensitive

(b) α-lipoic acid (see latter)



ALBINO: Human albino eyes show abnormal fovea and chiasmatic projections in addition to lack of pigment (melanin)



ALCAM/CD166: Activated Leukocyte Adhesion Molecule. A cell surface marker associated with stem cell characteristics



ALDH: Superfamily of aldehyde dehydrogenases



ALEFACEPT: LFA-3 Ig fusion protein; may help psoriasis



ALF: Annexin A6 LINE-2 fragment. Potent T-cell silencer



ALG-2: Apoptosis-linked gene 2; a Calcium-binding protein required for apoptosis of T-lymphocytes



ALI: Acute lung injury



α-LIPOIC ACID: (Thioctic acid; 6,8-dithiooctanoic acid); has 2 sulphur atoms joined by a disulphide bond; considered a powerful lipophilic anti-oxidant; found naturally in nature in plants & animals and is easily absorbed; said to maintain the tissue levels of ubiquinolone, glutathione and ascorbic acid, although its relationship with the (oxidizing) H2O2, that is believed to be generated by ascorbate within the extravascular compartment, is not clear; may benefit patients with Type II diabetes mellitus by protecting the insulin receptor (although clinically, Omega-3 fatty acids may be better); oral administration is claimed to decrease viability and growth of Ehrlich ascites carcinoma tumours in vitro & vivo, and induce p27Kip1-dependent cell cycle arrest in a breast cancer cell line



Alix: ALG-2 interacting protein X (AIP1).Protein involved in the curvature of endosome membranes; probably a functional ties between ESCRT II & III
in mammalian cells. It associates with lysosomes with LBPA, a lipid found exclusively in ILVs & MVBs of late endosomes



ALK1: Activin receptor-like kinase-1



ALKANES: Family of organic compounds with general structure CH3-(CH2)n-CH3



ALKYLATE: The transfer of one alkyl group from one molecule to another



5-ALKYNYLFUCOSE: Inhibits the production of GDP-fucose



ALLN: N-Ac-Leu-Leu-Norleucinol; calpain inhibitor I



ALPORT SYNDROME: Leads to renal failure, deafness and retinopathy; associated with mutations to collagen α3(IV), α4(IV) or α5(IV)



ALS: Amyotrophic lateral sclerosis; See VAP-B/C. Transgenic mice expressing the human superoxide dismutase 1 (SOD-1) mutant at position 93 develop a phenotype that is very similar to the human condition. Chronic Li+ administration to mice may attenuate the disease progress and reduce glial proliferation. However, clinical trials in humans have been disappointing



ALR: Absent in melanoma [AIM]-like receptor



ALSTERPAULLONE: A Paullone active against GSK-3



ALUMINIUM FLUORIDE: A non-specific G-protein stimulator



α-2-M: α-2-Macroglobulin. Its receptor is LRP/CD91



α-MANNOSIDASE II: A marker for the medial Golgi



AMANTADINE: Adamantan-1-amine; Dopamine releaser - helpful in Parkinson's disease



AMASTIGOTE: An early stage in the life cycle of (generally parasitic) flagellated protozoa (eg Trypanosomatids, Leishmania)



AMBP: α-1-microglobulin; a serum component; see bikunin



AMBRA1: Activating molecule in BECN1-regulated autophagy; see BECN1



AMD: (a) Auto-modification domain (as in PARP-1)

(b) Actinomycin D; extracted from soil bacteria of the Streptomyces genus and used as an antibiotic, then as an anti-cancer chemotherapeutic agent; by binding to DNA at the transcription initiation complex, it blocks RNA chain elongation



AMF: Autocrine mobility factor - See PGI; Glucose-6-phosphate isomerase. Often over-expressed in tumours



AMFR: Receptor for AMF. Tumour cell migration can be stimulated by the AMF-AMFR union



AMILORIDE: A chemical that inhibits the NHE antiporters, blocking the intake of Na+ in exchange for H+, thereby blocking correction for, or causing
acidosis; inhibits uPA; see ASIC & DEG/ENaC



AMINO ACIDS: Abbreviations :

Name

Three letter

One letter

Alanine

Ala

A

Arginine

Arg

R

Asparagine

Asn

N

Aspartate

Asp

D

Asparagine/aspartate

Asx

B

Cysteine

Cys

C

Glycine

Gly

G

Glutamine

Gln

Q

Glutamate

Glu

E

Glutamine/glutamate

Glx

Z

Histidine

His

H

Isoleucine

Ile

I

Leucine

Lue

L

Lysine

Lys

K

Methionine

Met

M

Phenylalanine

Phe

F

Proline

Pro

P

Serine

Ser

S

Threonine

Thr

T

Tryptophan

Trp

W

Tyrosine

Tyr

Y

Valine

Val

V



6-AMINONICOTINAMIDE: Inhibits the pentose pathway; probably blocks G6PD. It causes neurotoxicity



AMINOPHOSPHOLIPID TRANSLOCASE: The enzyme that maintains the asymmetrical arrangement of phospholipids within the plasma membrane
(eg phosphatidylserine, most phosphatidylethanolamine and phosphatidylinositol on the inner leaflet, with sphingomyelin on the outer)



AMINOTRIAZOLE: (Amino-1,2,4-triazole) An inhibitor of endogenous catalase activity



AML1: Transcription factor; may be influenced by Foxp3. See Runx1



AMPA: α-Amino-3-hydroxy-5-methylisoxazole-4-propionic acid (or salt); an agonist for glutamate receptors of the GluR1 type; can be a target for
Caspase I in neuronal apoptosis; the receptor and associated proteins may be palmitoylated, and disturbing this complex may have important effects



AMPHI- : (Greek) 'On both sides'



AMPHIBOLIC: Ambivalent



AMPHIDICOLIN: Blocks cell cycle progression, stopping in G1



AMPHIPATHIC: Relating to molecules that contain groups with opposing characteristics (eg having both hydrophobic and hydrophilic groups)



AMPHIPATHIC PEPTIDES: Certain peptides can enter cells through the plasma membrane, with amphipathicity not being essential, although this characteristic may delay the washout



AMPHIPHILIC: A molecule with an hydrophilic, polar group attached to a long hydrocarbon chain, with an hydrophobic, non-polar group at the other
end. Such molecules can be carried by lipoproteins in the blood and attach to the plasma membranes of cells



AMPHIPHYSIN 1: A brain-specific protein enriched at the synapse and a major binding partner of several components of the clathrin-mediated endocytic machinery, enhanced by the interaction of amphiphysin with dynamin. Directly stimulates clathrin recruitment onto liposomes (in an in vitro assay). Intra-molecular interactions between the amphiphysin COOH-terminal SH3 domain and its internal poly-proline region may regulate clathrin recruitment onto membranes, the poly-proline groups seem essential for cross-linking



AMPHIREGULIN: An autocrine growth factor secreted by keratinocytes



AMPHISOME: A component of the early endosome, being autophagic vacuoles fusing with the endosome and becoming acidified; they contain low level, but potent, proteolytic enzymes



AMPHITROPIC: Such proteins are able to bind to a cell's plasma membrane bilipid layer



AMPK: AMP-activating protein kinase, 190 kDa; phosphorylates HSL and Glycogen synthase; a key component of the sensory mechanism for cellular energy and a mediator of effect. It plays a part in bone formation and may be activated by metformin and TZDs. It has 3 subunits, α (isoforms α1 & α2), β & γ, that
must be combined for full activity. There is a complex interplay between AMPK, AMPKK AMP & ATP.



AMPKK: Kinase upstream of AMPK, 195 kDa, activating the latter by phosphorylation. It, and AMPK are activated by AMP



AMPK: AMP-activated protein kinase;



AMP-PMP: 5'-(β,γ-imido)triphosphate tetralithium salt; a non-hydrolyzable ATP analogue which competitively inhibits ATP functions



AN: Anisomycin, from Streptomyces griseolus; inhibits protein synthesis by preventing peptidyl transferase activity; can induce apoptosis in some cells;
potent JNK and MAP agonist



6-AN: 6-Aminonicotinamide



AN2: The mouse homologue of MCSP



ANACARDIC ACID: From cashew nuts; inhibits p300 &/or pCAF; cells are not very permeable to it



ANASTROZOLE: An aromatase inhibitor (used in breast cancer treatment)



ANAVEX1-41 & 2-73: Muscarinic ligand/Sig-1R agonist; may treat Alzheimer's Disease



ANC: Absolute neutrophil count



ANG II: Angiotensin II; stimulates proximal tubule sodium and water reabsorption



ANGELMAN SYNDROME: Defective Chromosome 15q11-13; Neurological problems with flat head, developmental delay, speech impairment, fits, insomnia, defective movements and balance, and bursts of laughter: the 'happy puppet'. Has defective ubiquitin function. May be associated with prolonged in vitro cell culture and epigenetic imprinting.



ANGIOZYME: A 35 nucleotide modified ribozyme



ANGPTL3: Angiopoietin-like 3 protein



ANISOMYCIN: Inhibits protein synthesis; can precipitate 'ribotoxic stress'



ANK: Often referred to for Ankyrin repeats, which may occur in other proteins and can participate in diverse interactions. See Ankyrin



ANKYRIN: A primitive family of membrane adapter proteins with multiple isoforms by alternative spicing, that mediates attachment of specialized domain membrane proteins (~7) to the cytoskeleton; 3 domains - conserved ankyrin N-terminal 22-24 tandem repeats domain (ARD) of 33 aa (divided into subdomains S1-4), a spectrin-binding domain (62 kDa) and a variably-sized C-terminal regulatory (death) domain 12 kDa, that can associate with death domains in other proteins, and a regulatory domain; links the Na+-K+-ATPase to spectrin in many cells; binds to the α1 subunit and is involved in trafficking and anchoring of the enzyme. The 33 repeats are not individually folded. Types are Ankyrin B (isoform 1 Ankyrin B220 [isoform 2 440 kDa in younger] & 135 kDa; neurons & glial, broadly, Chromosome 4), Ankyrin G (giant & general, limited to the brain & axons; 480 & 270 kDa; brain, axon; Ranvier) and Ankyrin R (RBC & restricted, neurons, Chromosome 8). Ankyrin has a high affinity for the C-terminal of IP3R (motif GGVGDVLRKPS), and AnkyrinB, Sigma1 and IP3R-3 form a complex. The AnkyrinB 33 aa repeat (consensus) is :

-G-TPLH-AA—G---VV--LL--GA--N--T-

Cell differentiation, cell cycle control & transcription

IA..........................D...A-

This can be associated with an extracellular motif EGF

The 12aa repeat in AnkyrinB440:

HPPVSPS-KTEK

S...................R DR

Ankyrin G has a serine-rich 40 kDa domain with similarities to mucins and glycoproteins; there is a wide diversity of subtypes and splice variants - truncated forms tend to be involved with the Golgi (119 kDa), lysosomes (100-120 kDa) and SR (26 kDa). Ankyrin G, if fully extended, may reach 0.5 μm. They associate with CAMs, tubulin, microtubules and clathrin (KD nM range; 4th subdomain of ankyrin & terminal knob domain of clathrin). L1 CAM contains an highly conserved motif for binding to ankyrin: EDGSFIGQY which is found in others of the L1 CAM family. Ankyrin-G and β-2 spectrin have a particular affinity and combine to allow creation of lateral membranes (eg to allow the columnar form). The binding site for ankyrin on E-cadherin is :


KEPLLPPEDDTRDNVYYYDEEGGGEED

for ankyrin on N-cadherin is :

KQLLIDPEDDVRDNILKYDEEGGGEED (differences underlined)



ANNEXIN: A conserved, large family of proteins which bind in a Calcium-dependant way to acid phospholipids (negative charge), and which contain a 70 aa Annexin repeat. Not found in yeasts. Former names: synexin, chromobindins, calcimedins, lipocortins, and calpactins. Over 160 types: have a structural fold, the annexin domain of 4 annexin repeats. Consist of a 'head' or 'tail' (~16 - 40 aa; 3 kDa) and core (terminal-COOH; ~33 kDa), the latter having the calcium and membrane binding sites. Benzodiazepines bind to them (significance ?). Each homology unit has an endonexin fold. Derivation is indicated by an alphabetical:
A = human, B = animal, C = fungi, moulds/similar etc. Head binds to S100 family (S100A10 or 11). Calcium may affect membrane binding by the core, and free up the NH2-terminal for ligand binding.



ANNEXIN A1 (Lipocortin I): Similar to Annexin A2. It binds ATP, also endosomal & transferrin-accessible. It binds to negatively- charged phospholipids
I n an ionic way, pyrimidine DNA fragments and purine clusters of RNA. It stimulates DNA synthesis



ANNEXIN A2: = Annexin II. 36 kDa (p36), a protein associated with the later glycolytic enzymes, especially GAPDH. Also links with p10 & Calcyclin. Can be non-membrane and cytosolic. It may be able to associate with membranes (eg ER) in a calcium independent way, but usually with a protein ligand. It associates with actin in a Calcium dependent way, at sites of cholesterol-rich membranes, and associates with Spectrin; is involved with rafts/actin at plasma membrane, involving phosphatidylinositol (4,5)-bisphosphate, Annexin A6 & F-actin and CD44. It binds tPA and, on the plasma membrane form the binding site with β2-glycoprotein I, for the phospholipid autoantigen.  It can interact with carbohydrates and mRNA, the latter in a distinct polysomal subpopulation. PKC phosphorylates, involved in regulated exocytosis. Oxidative stress can result in S-Glutathiolation at Cysteine-8 (as after TNFα). Heat stress results in phosphorylation of Tyr28, association with S100 A10 and translocation to the exterior of the plasma membrane of endothelial cells. Binds to S100A10, S100A6 & S100B



ANNEXIN A13: Involved in apical vesical transport in polarized cells



ANNEXIN V: ~33kDa. Binds to phospholipids (Calcium dependent). Used to detect the shift of phospholipids from the internal aspect of membrane, to the external during early apoptosis (loss of phospholipid asymmetry); a fluorescent dye taken up by cells undergoing apoptosis; used in flow cytometry studies. Often used to indicate apoptosis (caspase +) but it can also show positive results in the absence of mitochondria



ANNINE-6: A fast voltage-sensitive dye



ANOIKOS: Apoptosis induced by reduced cell contact



ANOVA: Analysis of variance (statistical protocols)



aNSC: Adult neural stem cell



ANT: Adenine nucleotide translocator; in mitochondrial wall, facilitating the exchange of cytosolic ADP with mitochondrial ATP; may be inhibited by
RIP, thereby increase cytoplasmic ROS



antCN27 (ant-CaMKIINtide): Precursor for tatCN peptide



ANTH: AP180 N-terminal homology, similar to ENTH but with an extra helix; binds PtdIns(4,5)P2, but the latter probably cannot provide for the lipid
bilayer penetration by ANTH



ANTI-CD20 TYPE:

Type I (eg Rituximab) redistribute CD20 into membrane lipid rafts and potentially activate complement

Type II (eg Tositumomab) do not activate complement but are more effective with PCD and mAb (in vivo), with F(ab)'2 fragments able to
provide immunotherapy. (Univalent fragments may be ineffective.) The receptor is unknown



ANTIGEN PEPTIDE: A small fragment of a protein antigen. For MHC class I they are 8-9 aa long and show preferential binding and derived from the
endoplasmic reticulum; the binding groove may be closed at both ends. For MHC class II they are 13-17(+) aa long, have limited variety and are derived from vesicles (endosome or lysosome) or the extracellular environment. The groove may be open at one end allowing longer peptides (N-terminus innermost); the molecule extending outside the MHC class II groove may be 'pruned' by carboxypeptidase



ANTIGEN PRESENTING CELLS: Monocytes with Major Histocompatibility (MHC) types I or II which, in combination with fragments of antigen,
effect sensitization of T lymphocytes. Dendritic cells particularly potent.



ANTIMYCIN A: Inhibitor of mitochondrial Complex III



ANTIOESTROGEN: A drug that inhibits the action(s) of oestrogen hormones. Tamoxifen is an early example. Anti-oestrogens induce both apoptosis and a pro-death autophagy in sensitive cancer cells



ANTI-VIRAL RESPONSE (Interferon): Sensing is by a mitochondrial-associated complex comprising RIG-1, RIPK1, FADD & TRADD



ANTOPAIN: A protease inhibitor



ANTIPORTER: Ion conducting channel, such as Na+/H+ antiporter, which protects against intracellular acidosis



ANTISIALO-GM1: Antibody that depletes NK cells, but also reduces some CD8+ T cells



AnV: Annexin V



ANXA1-13: Genes for Human Annexin-1 to 13



AO: Acridine orange



AOA: Amino oxyacetate; inhibits the Aspartate-Malate shuttle



AOCLD: Acute-on-chronic liver disease



AOM: Azoxymethane



AOM-DSS: Azoxymethane-dextran sulphate sodium; a protocol to induce murine colon cancer is to give an injection of AOM, followed for 1 week with the DSS is in the drinking water (to cause inflammation)



AP-1: Activating protein-1. A gene promoter comprising a collection of dimer complexes derived from Fos & Jun. Jun:Jun homodimer or Fos:Jun heterodimer activate the AP-1 site, (which is known as TRE) in the regulatory domain, and activate the transcription of the gene concerned.. See c-Jun, c-Fos. Gene transcriptions activated include :

Various neuropeptides
Neurotrophins
Receptors
Transcription factors
Enzymes involved in neurotransmission
Proteins that bind to cytoskeletal elements



AP-1 SITE: A DNA motif of TGAGTCA, found in the promoter of diverse genes



AP-1 to -4: Heterotetrameric adapter proteins associated with clathrin and involved in recognition of cargo through peptide motifs:

Adapter protein subtype

Subunits

AP-1

γ-β1-μ1-σ1

AP-2

α-β2-μ2-σ2

AP-3

δ-β3-μ3-σ3

AP-4

ε-β4-μ4-σ4



AP1 - 3 have many isoforms; link with clathrin, AP-4 may be a component of a non-clathrin coat; recognize the "dileucine-based" consensus motif
and the YXXΦ motif

AP-2: Heterotetrameric adapter protein associated with clathrin; binds to clathrin to initiate pit formation; also binding to cargo to initiate the endocytosis.
Subunits : Large α & β2

Adaptin – Medium μ2, binds to the YXXΦ motif on receptors (if present) and ubiquitin
Adaptin – Small σ2

Probably not an essential structural clathrin coat component for function, but without it, the number of coated pits is greatly reduced



AP180: Important in the cycling of synaptic vesicles and the sorting of synaptobrevin; early at the membrane (with epsin) for clathrin pit formation



APAAP: Immunological alkaline phosphatase tissue staining process



APAF1: Apoptotic protease activating factor-1; binds cytochrome c. With ATP/dATP and procaspase-9, forms the Apoptosome in the cytoplasm, leading
to apoptosis.



APB: (a) DL-2-amino-4phosphonobutyric acid. An inhibitory agonist at outer nuclear bipolar cells (retina)

(b) 2-aminoethoxydiphenyl borate; membrane-permeable, IP3R modulator; blocks SOC channels in the plasma membrane; modulates TRPV1-3
& TRPM2; can be agonist at low concentrations, antagonist at higher concentrations; activates Ca2+ influx through Orai3



APC: Gene for adenomatosis polypi coli (APC) protein. Mutations generally result in truncated forms of the protein.



APC: (a) Antigen Presenting Cell(s); two main types - 'Professional' (DC, macrophages & B cells), very efficient and 'non-professional', with lesser
efficiency. The latter have lower levels of MHC, and are more involved in tolerance (Treg)

(b) Adenomatosis coli (protein); a large protein that binds to several members of the Wnt/β-catenin pathway, a negative regulator of β-Catenin stability (generally) but can be positive, depending upon compartmentalization; found attached to the basal cortex of colon epithelial cells and acts a template for microtubule network formation. Mutations result in the accumulation of much β-Catenin and β-Catenin-Tcf activity. It has a structural role and may be involved in microtubule attachment to the plasma membrane; a +TIP; may sensitize murine cultured cells to activation by TRAIL via downregulation of cFLIP

(c) APC: An Ubiquitin ligase; Anaphase promoter complex, activated by Cdh1



APCA: Anti-Purkinji cell antibodies



APCL: Adenomatosis polyposis vice-like



APD: Action potential duration



APE1: Apurinic/apyrimidinic endonuclease 1; redox factor 1



APECED: Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy



Aph-1: A scaffold protein; part of γ-Secretase



APHIDICOLIN: Phosphorylates Chk1 and causes activation of checkpoint halt to mitosis using ATR



APICIDIN: An HDAC inhibitor



aPKC: Atypical PKC, a family that lacks Ca2+ binding domain and has one Zinc finger, making it unresponsive to Ca, diacylglycerol and phorbol esters. The regulatory domain differs from the PKCs. Src binds to the aPKC1 through the Src homology 3 domain (SH3) and residues 98-114 in the aPKC regulatory domain.



APL: (a) Anti-phospholipid antibodies

(b) Altered peptide ligand. If a ligand can be charged to be less effective, it creates a weaker response



APM1: The product of the gene in Chlamydomonas is unknown. It may encode a microtubule-associated protein needed for spindle function



APO(A): Apolipoprotein a; combines with LDL (Apolipoprotein-B100) by a disulphide bond, creating Lipoprotein a [Lp(a)]; synthsized in the liver; there are 2 non-covalent groups formed, KIV-7 of Apo(a) to Lysine 680/690 of ApoB-100, and KIV-8 of Apo(a) and ApoB-100; these then combine to for a disulphide link between the Apo(a) and ApoB-100; the isoform sizes vary greatly because of copy number variations in KIV-2



APO-1: Anti-Fas Antibody; See CD95



APOE: Apolipoprotein E



APOCYNIN: Nox inhibitor; prevents assembly of Nox enzyme complex



APO-2L: See TRAIL



APOLIPOPROTEIN C1: Water soluble, 7.4 kDa, largely associated with HDL.



APOPTOSIS: Generally considered to be a planned cell death by an inbuilt shut-down protocol (cf necrosis), however, it is more a mechanism for disposal of cell parts - death can still proceed without apoptosis, by necrosis (eg when there is a deficit of ATP, the apoptosis activating when the ATP level rises). After oxidative stress (which causes ATP levels to fall) apoptosis cannot resume until the ATP level is ~25% the basal level. In vitro apoptosis takes about 2 h for DNA damage to become apparent; endonucleases break down DNA to oligonucleotide fragments, producing a characteristic 'ladder' pattern on electrophoresis, with initial DNA fragments ~50(-300) kb and later break-up into nucleosomal-sized units. There are other tests, eg TUNEL. An intact and active oxidative phosphorylation is required for effective apoptosis. The phospholipid membranes change charge, from negative to positive. The enzyme(s) responsible have been contentious :

DNAse I Involved in tissues with high turnover, but not apoptosis
DNAse II Lysosomal enzyme; possible active early (then destroyed). It is used by phagocytes that have engulfed nuclear debris

DFF DNA fragmentation factor, downstream from the caspase 3, splitting off DFF45, which causes DNA fragmentation. It appears to be a complex of CAD
& ICAD

CAD = CPAN Caspase activated DNAse = caspase activated nuclease, inhibited by ICAD. Most species have a basic protein ~40 kDa, pI 8.7-9.5. It binds
to DNA without Mg2+ and endonuclease activity at neutral pH with Mg2+, specific for double-stranded DNA.

In vitro apoptosis of DP thymocytes induced by Dexamethasone is inhibited by cyclohexamide; the thymocytes up-regulating CD3/TCR CD69 CD25.

Cells undergoing apoptosis, and that are not recognized and removed by phagocytosis promptly break down, referred-to as secondary necrosis. Cell surface changes may include oxidized phospholipids. Macrophage receptors include SR-A, SR-B1, CD36, CD68 and CD14. See also Autophagy, Autoschizis, LCD

Mitochondria fragment early in the process, after Bax/Bec oligomerization but before activation of caspases



APOPTOSIS-LIKE CELL DEATH: Does not involve the caspase-3 DNA fragmentation, but can be caused by lysosomal proteases and mitochondrial factors, such as AIF



APOPTOSOME: Large complex of Apaf-1, cytochrome-c and procaspase-9. The latter is then activated to activate Caspases-3 & -7



APP: (a) Amyloid precursor protein; cleaved to amyloid-β peptide, involving β-site APP cleaving enzyme (BACE1) and γ-Secretase

(b) Acute phase protein (eg C-reactive protein)



APPBP1: Amyloid-β-precursor protein-binding protein 1



APRIL: A proliferating-inducing ligand; a member of the TNF family and shares some receptors with BAFF (see BAFF). They are involved in B cells and tolerance. It is cleaved in the Golgi before release and only exists in the secreted, soluble form. It can from a fusion protein with TWEAK, forming TRE-PRIL. It is produced by macrophages and epithelial cells and many cancers are associated with elevated levels. It cannot compensate for the loss of BAFF. Genetic factors may implicate it in Japanese SLE. In some tumours where there is over-expression of APRIL, there may be an over-expression of a heparan sulphate proteoglycan, which is a co-receptor for both APRIL and TACI



APROTININ: Protease inhibitor



APS: Adenylylsulfate; sulphate -O- bonded to the 5' phosphate of Adenosine monophosphate



APS-1: Autoimmune poly-endocrine syndrome-1: see AIRE



APT1: Acyl-protein thioesterase-1; removes palmitate from G proteins and other acyl protein substrates



APV: DL-2-amino-5-phosphonovaleric acid. An antagonist at NMDA receptors



APYRASE: (Usually extracted from potato, with varying features) An adenosine 5'-triphosphatase and an adenosine 5'-diphosphatase mix. See ARL67156



AQP1 & 2: Aquaporin1 & 2; may be able to transport HCO3-

AQUAPORIN-2: Vasopressin-regulated water channel of the renal collecting duct

AQUAPORIN-5 (AQ-5): A marker for Alveolar type I (AT1) cells



AR: (a) Activating receptor

(b) Androgen receptor. It resides mainly in the cytoplasm and associates with heat shock proteins in an inactive state before androgen binding. With androgen binding, there is a conformational change and translocation to the nucleus and binding to promoter elements. When the AR of prostate cancer cells is reduced/ablated (eg by siRNA), there is reduction of Bcl-xL, which is associated with massive apoptosis, whether the AR was hormone responsive or not. Deficiency of class 1 UDP glucuronosyltransferase enzymes has been identified in the stem cells, and appears involved in androgen metabolism in prostate cancer



AR18: A selective inhibitor of GSK3



AR-A014418: A thiazole urea molecule that is specifically very inhibitory for GSK-3β but has poor brain penetration



ARABINOGALACTAN: Densely branched polysaccharides MW 10,000-120,000, obtained from the larch tree, Galactose:Arabinose 6:1, with a trace
of Uronic acid. It is soluble and stable, with minimal/no toxicity; an immune stimulant



ARACHIDONIC ACID: 5,8,11,14-Eicosatetraenoic acid. An unsaturated, omega-6 fatty acid found in cell membranes, from which it is released by Phospholipase A2 in response to inflammation, converted to prostaglandins by involving COX1 & 2, and to leukotrienes by p450-catalysed metabolism. It binds to the α-subunit of G-proteins and inhibits Ras GTPase-activating proteins



ARC: (a) Average reflection coefficient

(b) Arachidonic acid dependent Ca2+-selective channel



ARCADLIN: Associates with N-cadherin and cadherin-11; may stimulate endocytosis of N-cadherin



ARD: Ankyrin repeat domain; N-terminal region has 24 tandem array of ankyrin repeats; interacts with membranes



ARDS: Acute respiratory distress syndrome; a pulmonary component of multi-organ failure, as can occur in sepsis



ARE: (a) AU-rich elements; as reiterations of AUUUA, or oligo(U)4-7 sequences in an AU-rich context; are binding sites for cytoplasmic and
nuclear proteins

(b) Androgen response element; specific cDNA sequences, typically 5'-tgttct-3'

(c) Active-resistive exercise



ARECOLINE: Agonist of cholinergic, muscarinic receptors that can be coupled to PLA2



ARF: ADP-Ribosylation factor; a small GTP-binding protein and Ras-like GTPase. Its reactions are blocked by Brefeldin A when in association with
Golgi proteins



ARF1: Recruited by GTPase exchange proteins, essential for COP-I regulated vesicle budding in Golgi



ARFGAP: ARFGAP1, a GTPase-activating protein (GAP) for ADP-ribosylation factor 1 (ARF1), couples to either BARS (see Kif3) or endophilin B for
vesicle formation by the coat protein I (COPI) complex



ARG8: Yeast; mammalian orthologue is LC3



ARL: See ARL67156



ARL67156: An inhibitor or ecto-ATPases; artificially increase the extracellular ATP concentration



ARGONAUTE: Small proteins that associate with microRNA; see under Ago



ARGOSOME: Exogenously-derived lipoproteins



ARH: A protein with a phosphotyrosine-binding domain; involved in clathrin function



ARH77: Cell line; Multiple myeloma, EBV+



ARHR: Autosomal recessive hypophosphataemic rickets/osteomalacia; have inactivating mutations on the DMP1 gene (chromosome 4q21)



ARIA: See neuregulin



ARK: Aurora like kinases. 2 subfamilies.



ARMADILLO: The Drosophila orthologue of β-Catenin. A conserved sequence that is required for the protein-protein interaction between KAP3 and the Kif3 cargo: a sequence of amino acids forming α-helix coiled-coil domain that is repeated. Seems to be involved in intracellular signalling Wnt/β-Catenin (E-cadherin and APC) and microtubular motor activity. Similar repeats occur in SpKAP115/KAP. See also p120-catenin



ARP: Aldehyde reactive probe



ARNT: ArR nuclear translocator which, with AhR/ligand triggers transcription of target genes, such as CYP1A1 & CYP1B1 and several transferases



AROMATASE: A member of the P450 superfamily of monooxygenases and catalyse many reactions in storoidogenesis; inhibitors to it are important therapeutically, because they can block the conversion of steroid hormones to oestrogen (or similar) in patients with hormone-responsive breast cancer



ARP: Actin related protein. Dynein contains Arp1 & Arp11 and Actin



ARRESTIN: Proteins that inhibit phosphorylated GPLRs stoichiometrically; visual arrestins (limited expression) & βarrestins (widely expressed). They recognize both the activated receptor and the associated GRK phosphorylation site. They serve as adaptors and ferry signalling components to activated receptors. The βarrestins may be responsible for the acute & chronic opioid behavioural effects, although opioid withdrawal symptoms may involve other mechanisms

βarrestin-1 : main arrestin in the brain; generally post-synaptic. MS patients may have antibodies to this

ARRESTIN-2: Binds to the COOH-terminal region of p105NF-κB, blocking the phosphorylation that would release Tpl2 from p105

βarrestin-2 : found in brain in lower quantities than -1, but more potent.



ARROW: See LRP5/6; Co-receptor for Frizzled



ArsC: Plasmid Arsenate reductase that uses Glutathione to convert Arsenate to Arsenite. In E. coli R773, it has 141 aa, 14.8 kDa with a catalytic Cysteine and needs Glutaredoxin in addition for a quaternary complex. The GSH thiol is needed for catalysis, but not for oxyanion binding; its role involves structure. The E. coli enzyme is unique, with water molecules surrounding the surface (>100% of predicted), with Caesium a cofactor (7-10 sites). There are three sulphate attraction sites and a fourth bisulphite site and can act as an enzyme for such a conversion. These enzymes may be related to phosphatases phylogenetically, but show no phosphatase activity. Oxyanions (sulphate) change the surface charges dramatically, and change activity, especially for Glutaredoxin.



ARSENIC (As): Atomic weight (12C) = 74.9216, Ionic radius = 0.69 Å. Toxic element, generally found in the pentavalent Arsenate (V) form. It can be reduced in vivo to Arsenite (III) which, with metabolites, is much more toxic. In vivo, inorganic Arsenic mimics inorganic Phosphate. Enzymatic reduction is dependent upon Glutathione & glycolytic substrates and is inhibited by inorganic phosphate. It can react with thiols, especially dithiols.



ARSENITE: Inhibits pyruvate dehydrogenase complex



ART: Assisted reproductive technologies (eg in vitro fertilization)



ARTC1: Antigen recognized by Treg cells-1. It is a natural cancer ligand antigen that modulates Tregs to suppressor effects; expressed by tumours and
testis, with minimal amounts from other tissues. The tumour cells may be the major presenters of the Ag to the TILs. The gene ARTC1 is mutated in cancers



ARTEMISININ: An antimalarial drug; resistance is emerging



ARYL: Organic compounds formed on an aromatic ring



As: (a) Arsenic (See Arsenic)

(b) Antisense



ASARM: Acidic serine-aspartate-rich motif; found in the C-terminal fragment of MEPE; phosphorylated ASARM peptides inhibit bone mineralization
and renal phosphate reabsorption; PHEX binds to MEPE via ASARM, MEPE inhibiting PHEX enzyme activity; hydrolysed by PHEX



ASC: (a) Adipose stem cell

(b) Apoptosis-associated speck-like protein containing a caspase-activation and recruitment domain (CARD); an adaptor complex found in inflammasomes that recruits procaspase-1; the latter is cleaved to release caspase-1, which then cleaves pro-IL-1β & pro-IL-18 to release the active cytokines; there may be some ASC activity independent of the inflammasome in EAE; ASC is not essential for NLRP1 activity, but enhances it; ASC & NLRP3-dependent necrosis seems essential for an adequate murine immune response against bacteria, but in an human cell line, the necrosis is not blocked by suppressing RIPK1 with Nec-1; a requirement for Cathepsin B activation is not obligatory



Asc2¯: Ascorbate dianion; see ascorbate

Ubc*¯: Semidehydroascorbate (ascorbate radical); see Ascorbate

AscH¯: Ascorbate monoanion; see ascorbate

AscH2: Ascorbic acid; see Ascorbate



ASCIZ: ATM substrate Chk2-interacting Zn2+-finger protein; see ATMIN/ZNF822 also; a protein with a dual role – DNA damage response and transcription factor; involved in the survival of developing B-cells



ASCOMYCIN: A FK506-like agent; blocks Calcineurin phosphatase action on NFAT



ASCORBATE: Generally known as Vitamin C; an anti-oxidant and co-factor for a number of enzymes, with 2 ionizable hydroxyl groups, with pK1 of 4.2 and pK2 of 11.6, with 'typical' serum levels of 40 – 80 μM; as a reducing agent, it is oxidized to the ascorbate radical Asch·¯ & HDA, the Asch·¯ being relatively unreactive, being able to be reduced back to ascorbate by NADH- and NADPH-dependent reductases. At physiological pH (~7.2) the dominant form is AscH¯, with conversion to Asc2¯ increasing x10 for every 1 pH unit rise; intracellular ascorbate is higher than extracellular (except in RBSs), particularly myeloid & lymphoid cells and especially the adrenal and pituitary glands and eye; the transport there may take hours (cf DHA). Gross deficiency results in the clinical condition scurvy; it may not have been added to human cell cultures, with ascorbate 2-phosphate being the physiological relevant form. It has been used in cancer treatment, but oral dosing can produce a blood level of only ~0.2 mM, which is considered inadequate to have any appreciable anti-cancer effect. Higher levels are attained by intravenous administration. The anti-cancer effects are attributed largely to the local generation of H2O2, an oxidizing agent (ie reducing effect initially ⇒ oxidizing effect locally). Oxalate can be a breakdown product but, if treatment courses are of limited duration, may not be important. Other direct or indirect influences are on iron metabolism, the release of AIF from mitochondria, increasing expression of p53, p21 and cellular Calcium, decreasing mitochondrial membrane potential and activation of caspase 3, reducing the level of HIF-1, with reduced myc-mediated tumorgenesis, inhibition of COX-2 and modulation of IGF-II production &/or caspase-independent autophagy. Enzymes of the Fe2+-2-oxoglutarate diogenase family require ascorbate to maintain full catalytic activity. Intracellular ascorbate requires oxidization to DHA, the facilitated uptake by the GLUT glucose transporters, and intracellular reduction back to ascorbate, which is trapped. Even at high intravenous doses, ascorbate as a monotherapy may not be curative for cancer. Catalase, added to cancer cells in culture, reduced the toxic effects of ascorbate, and the cytotoxic effects of Docetaxel, Epirubicin, Irinotecan and 5FU are enhanced by ascorbate; the effects of Oxaliplatin and Vinorelbin being relatively unchanged. Some leukaemia cell lines show growth stimulation in the presence of ascorbate; ROS produced by Ascorbate+Vitamin K3 stimulates autophagy but, when this was blocked, the ROS stimulated PARP1 which, in turn produced AIF, resulting in apoptosis; tissues with high levels of ascorbate may be able to have lower HIF-1 activation; there remains uncertainty on the nature of the anticancer effects that are described, whether due to HIF-1 &/or H2O2; ascorbate ↔ DHA by oxidation/reduction can be repeated many times; see HIF, collagen prolyl hydroxylase & histone demethylase

Dose of Ascorbic Acid

Plasma (steady-state)

200 mg p.o.

80 μM

Oral maximum dose

Plateau ≈ 220 μM

10 g i.v.

1 – 5 mM



ASCORBIC ACID: See Ascorbate



α-Secretase: ADAM10



ASIC: Acid-sensing ion channel



ASK1: (Apoptosis Signal-regulating kinase 1, MAP3K5)) A redox-sensitive protein MAPKKK involved in the ER stress response, activating by phosphorylation JNK & p38 by phosphorylating MAPKKs JNKK1/MKK4, JNKK2/MKK7, MKK3 & MKK6; activity depends upon redox status of thioredoxin – the reduced form binds to ASK1 & blocks; possibly being a major switch for the redox signal from TNF to activate JNK activity; H2O2 induces phosphorylation of Thr845 (human Thr838) which is inhibited by PDK1; ROS frees ASK1 from docking protein 14-3-3; implicated in ER stress-induced autophagy (with IRE1α activation); there are three main domains – C-terminal aa941-1375 responsible for PDK1 binding, kinase aa649-940 and N-terminal aa1-648; phosphorylation sites (+/- response) are Ser83(-), Thr845(+) & Ser967(-); PDK1 phosphorylates at Ser967; knockdown of PDK1 resulted in decreased phosphorylation level of Ser83 & Ser967, and an increased level of Thr838; Akt can phosphorylate Ser83, inhibiting ASK1's pro-apoptotic function and MPK38 & ASK2 can phosphorylate the autophosphorylation site Thr845 and stimulate apoptosis; PDK1, by phosphorylating Ser967, brings about binding of the site to 14-3-3

Inhibitors Stimulators

Thioredoxin Daxx

Glutaredoxin TNF/TRAF & Fas ligand

14-3-3 JSAP1

Hsp72 JIP3

Raf-1 MPK38

Akt Some chemotherapies

PP5 ER stress

p21CIP1 Calcium overload

Calcineurin

ASK2: Phosphorylates & activates pro-apoptotic ASK1 at Thr845 (the ASK1 autophosphorylation site)

Of three factors known to shift the balance towards apoptosis in vitro, TNF, H2O2 (ROS) and Calcium, when examined in the clinical stetting :

    1) Lithium can stimulate the production of TNF with a delay of ~20 h, the TNF can stimulate the TNFR to activate TRAF

    2) H2O2 can be produced in the interstitial fluid by intravenous doses of Vitamin C; some would be expected to move intracellularly

3) Hyperthermia, delivered by radio-frequency power fluxes may damage cell membranes (plasma membrane, mitochondrial membranes, those of the endoplasmic reticulum and endosomal/lysosomal structures) sufficiently to allow Calcium into the cytosol in a non-compartmental way; this could have profound effects upon Calcium-dependent enzyme systems, such as calcineurin, calpains, structural integrity (mitochondria & endoplasmic reticulum) and provide a stimulus for apoptosis or programmed cell death



    The means seem at hand to specifically target ASK1 and favour an apoptosis outcome



ASKIN TUMOUR: See PNET; Ewing's 'sarcoma', EFT



ASLV: Avian sarcoma-leukosis virus



ASM: Acid sphingomyelinase; may be activated by caspases-8 &-9; may have activity enhance by Hsp70, which aids binding to the lysosome membrane



αSMA: Smooth muscle marker



ASMase: Acidic sphingomyelinase. A sphingomyelin-specific phospholipase C that exists in 2 forms - a lysosomal and a secretory form. The secretory ASMase translocates onto the outer leaflet of the plasma membrane from intracellular, presumably vesicular stores, to release ceramide within the raft-associated sphingomyelin pool, generating the ceramide required for raft clustering; other stores are described inn the endosomal/lysosomal compartments



AS ODN: Anti-sense oligodeoxynucleotide



As2O3: Causes a block at metaphase, apparently due to perturbation of tubulin by promoting tubulin polymerization. This results in apoptosis. Has a
paclitaxel-like effect (See also Taxels)



ASP: (a) Abnormal spindle-like protein

(b) Agouti Signalling Protein



ASPP: Apoptosis-stimulating protein of p53 [alternatively, Ankyrin repeats SH3 domain & proline-rich region containing protein]; a family with 3 members -

ASPP1: Activates the p53 apoptosis function

ASPP2: Activates the p53 apoptosis function

An inhibitor (iASPP) of the p53 apoptosis function

ASPP1 & 2 regulate p53 target genes for apoptosis, but not those for cell-cycle arrest



Asp PROTEIN: in Drosophila; a possible GTBP



ASSEMBLIN (Striated fibre): A non-contractile linker protein in green algae; links centrioles and nucleus



ASTROCYTES: Major supporting (glial) cells of the brain. Markers, GFAP, and S100β



ASTROSPHERE: The spindle aster



α-Syn: (α-Synuclein) An unfolded molecule able to self aggregate to form oligomers and fibrillary polymers of β-Amyloid type; a major component of
Lewy bodies, found in Parkinson's disease.



AT: Ataxia-telangiectasia. Human genetic disease with mutations in ATM, showing degeneration of the Purkinje cells and other defects such as G1 arrest, reduction in DNA synthesis and G2 arrest. AT fibroblasts are sensitive to ionizing irradiation, but have little sensitivity to UV, alkylating agents or inhibitors of DNA replication.



AT-1/-2: Alveolar type I/II



A2t: Annexin2A-p11 heterotetramer



ATA: Aurintricarboxylic acid; blocks GAPDH & apoptosis; inhibitor of DNAse that is involved in the nucleosomal cleavage that produces the DNA
'ladders' seen in gel electrophoresis



ATACICEPT: Recombinant fusion protein, neutralizes B-cell stimulator and APRIL



ATCC: American Type Culture Collection - a supplier of standard cell culture lines



ATD: Average time to death



ATF2: Substrate for p38 ('stress pathway')



ATF6: Activating transcription factor 6; ER transmembrane stress sensor; binds to BiP in the ER membrane



ATG: Genes associated with autophagy

ATG4: Autophagy gene

ATG6: Yeast; mammalian orthologue gene BECN1; associated with tumour suppression

ATG32: Gene for a mitochondrial protein conferring selectivity for mitophagy in yeast



ATG: (a) Anti-thymocyte globulin

(b) Autophagy-related

ATG3: Associated with ATG7

ATG5: Associates with ER IP3R; sensitizes

ATG7: An autophagy-related E1-like enzyme essential for two ubiquitination-like reactions - ATG12 conjugation and LC3-lipidation; the FAP motif
is essential

ATG12: Associates with ATG7



Atg5, Atg12: Autophagy-related. Regulatory genes of the autophagy pathway; the products conjugate



ATL3: Atlastin 3



ATLASTIN 3: In a family of GTPases, & found on ER membranes as probably tethers to maintain normal structure; up-regulated in GBM



ATLL: Adult T-cell leukaemia/lymphoma



ATM: Ataxia-telangiectasia-mutated. Term used for a protein involved in DNA monitoring and repair. Protein kinase. Plays important role in response to ionizing radiation, controlling the initial phosphorylation of key proteins such as p53 at Serine 15, Mdm2, BRCA1, Chk2 and Nbs1 following DNA damage. Absence is not lethal - growth retardation and infertility.

α-TOCOPHERYL SUCCINATE: Redox-silent, Vitamin E analogue (cf α-Tocopherol)





ATOH1: A bHLH transcription factor



A-TO-I: Adenosine conversion to inosine (eg by ADAR)



α-TOS: α-Tocopheryl (cf α-Tocopherol)



ATP: Adenosine triphosphate; a general phosphate group donor. Intracellular level free ~400-600 μM, MgATP 3-8 mM, packed cells of Dictyostelium
discoideum
1 mmole/L, tightly controlled. Loss of intracellular ATP has been used as an indicator of cell death; ATP binding sites have general motif GXGXXG; seems to be necessary extracellularly for an immune response (T-cell based) to develop against cancer cells when treated with anticancer drugs (in mice); acts on Gq-coupled plasma membrane receptors with the production of Inositol-1,4,5-trisphosphate, the messenger ligand for the I3PR calcium channels; thereby releasing Ca2+ from the ER



ATPase II: MgATP-dependent aminophospholipid translocase; 'flipase'; inhibited by high Ca2+, acetyl phosphate, N-ethylmaleimide,
pyridyldithioethylamine; moves PS & PE against gradient



ATP BINDING SITE: Has a typical configuration :

- Gly - X - Gly - X - X - Gly - X14 - Lys -



ATR: ATM-Rad3-related protein. Sensitizes mammalian cells to all forms of DNA damage and diminishes the G2/M checkpoint response induced by γ-irradiation. Homozygous loss is lethal in early embryo, with mitotic catastrophe. Controls late phosphorylation of p53 in response to ionizing irradiation. It, and ATM control Chk1 & 2



ATR-X: Protein involved in chromatin remodelling; loss is associated with a poor prognosis in some cancers



ATRx: Gene for ATR-X



ATRASENTAN: An ETA receptor antagonist being trialled for preventing bony metastases



ATRIP: ATR interacting protein



AU: Adenosine-uridine dinucleotide



AUBPs: ARE-binding proteins, eg hnRNP A1 in activated T lymphocytes. Generally 32-40 kDa



AUC: Area under a/the curve



AUG: Adenosine-Urosine-Guanosine; Initiator codon sequence for DNA transcription by ribosomes



AURORA KINASE A: A negative regulator of p53 (as is HDM2, the two probably forming a complex; see also Pin1, HIPK2 & RITA etc.)



AURKA: (Aurora kinase A) A negative regulator of p53 (as is HDM2, the two probably forming a complex)



AUROPROBE: Usually the use of an antibody complexed to gold salts such as to form precipitates of gold particles that can be identified under
electron microscopy, and which localize the antigen being identified and located.



AURORA A: An oncogene involved forming a functional mitotic apparatus. A kinase which cooperates with a Polo-like kinase to recruit γ-tubulin ring complexes and microtubule associated proteins to assist spindle formation and separation. Required for the recruitment of Cyclin B/Cdk1 to the centrosome, prior to activation. Phosphorylates Cdc25B on Ser353, which is located at the centrosome. Loss slows mitosis, excess speeds up.



AUTAPSEs: Recurrent synapses forming in cell culture islands containing single neurons



AUTOLYSOSOME: The fusion product of an autophagosome with a late endosome or lysosome; after fusion, the inner membrane of the autophagosome and the contents are degraded by lysosomal hydrolases and reused by the cell



AUTOPHAGIC VACUOLE: See Autophagosome



AUTOPHAGY: The transfer of a cell's damaged organelles to its own phagosomes; it can be pro-survival (recycling) or a form of cell death that is independent of caspases; characterized by having cytoplasmic vacuoles and autophagosomes, an absence of marginated nuclear chromatin, an increase in cleavage of microtubule-associated protein 1 light chain 3 and a reduction of of p62/sequestosome-1 protein levels; three types –

Macroautophagy, requires the formation of a double membraned vesicle (autophagosome); can involve Atg5, 9, 12 & 16, LC3 & PE

Microautophagy

Chaperone-mediated autophagy

As a prosurvival mechanism, autophagy provides breakdown products to fuel energy sources (eg mitochondria)



AUTOPHAGOSOME: A double membraned vesicle for enveloping organelles & long-lived proteins for digestion and sequestration of toxic components; =autophagic vacuole; some 30 autophagy-related genes are identified



AUTORADIOGRAPHY: A flat specimen (histology section or filter paper/membrane) within which features are expected to be highlighted by an incorporated radioactive tracer, has applied to it a photographic film and the latter left to be exposed (usually hours to days). The film is then separated off the specimen and developed, to reveal the location of the radioactive 'hot-spots'



AUTOSCHIZIS: Morphological changes of a form of cell death observed in cell suspended in ascorbate &/or menadione (the latter more potent). There is nuclear lysis and a characteristic pinching-off of chunks of cytoplasm. The culture medium contained 10% foetal bovine serum, meaning that the ascorbate probably would have given rise to hydrogen peroxide in the medium (interaction unclear)



AUTOTHIXOTROPY: Clustering of water molecules in still & non-deionized water, providing resistance to movements



AUXILIN: J-domain-containing cofactor. Released vesicles rapidly lose their clathrin coats in a process mediated by the ATPase Hsc70, which is
recruited by auxilin. Accumulation of a specific lipid can recruit sufficient auxilin molecules to trigger un-coating at about the time of budding



AVSD1: Atrioventricular septal defect; See CCN



Awdk-pn: Awd mutation product of nm23-H1, defects in those with prune eye colour in Drosophila (killer of prune)



AXIN1: The gene for Axin1AXIN1

AXIN2: The gene for Axin2, an endogenous β-catenin target gene, used for assessments of β-catenin transcription activity (inverse of Wnt3A levels)



AXIN1: An axis inhibitor - a scaffold protein that binds GSK-3β and β-catenin, necessary for phosphorylation of the latter, but inhibiting GSK-3β; formation controlled by ERK/MAPK in some tumour cells; Axin1 phosphorylation by GSK-3 improves binding. Forms a rate-limiting platform for the Wnt/GSK-3β/Semaphorin1/PDZ-RGS3/FAM129B/β-catenin destruction complex, and inhibition of the complex augments TRAIL-dependent apoptosis of melanoma cells, in part by activation of p53 (possibly with GSK-3α/GSK-3β differences); activates MEKK1: compromised by GSK or Casein kinase Ie. It can bind to microtubules; axin1 levels are controlled by ubiquitin-mediated proteasomal degradation; other post-translational modification include methylation by protein arginine methyltransferase 1, PARsylation by tankerase-1/2 & SUMOylation

AXIN2: An inhibitor of GSK-3β



AXITINIB: A VEGF receptor tyrosine kinase inhibitor



Axl: (=ARK, Ufo, Tyro-7); Binds the ligand GAS6. See Mertk



AXONEME: The core structure of cilia and flagella - usually a ring of 9 pairs of microtubules (A & B, as in the centriole) surrounding a pair of
microtubules. Growth and resorption is at distal (plus) end



αVβ-INTEGRIN: Phagocytosis receptor



5AzaC: 5-aza-2'-deoxycytidine; a demethylating agent



AZAKENPAULLONE: GSK3 inhibitor



AZUROCIDIN: Heparin-binding protein



B1: A mAb against CD20; Tositumomab



2B4: A member of the SLAM receptor family



B7 SUPERFAMILY: Structurally related APC receptors with Ig domains, often inhibitory. Many are induced by activation :

B7.1 (CD80): Ligand for CD28; not expressed in the thymic cortex, but by APC (cortico-medullary) and medullary epithelial cells

B7.2 (CD86): Ligand for CD28; not expressed in the thymic cortex, but by APC (cortico-medullary) and medullary epithelial cells. It seems the
more important for EAE induction

PD-L1 (B7-H1)

PD-L2 (B7-DC)

BTLA (ligand HVEM)
Tim-3 (for Tim-3 ligand)



B16: Murine melanoma cell line



B23: A nucleolar protein



B43-GENISTEIN: A CD19 directed, apoptosis inducing tyrosine kinase



B-50: See GAP-43



B61: Ephrin A1, LERK1; part of the TNF signalling pathway



B220: A B cell lymphocyte marker; plasmacytoid dendritic cells; B220¯ NK cells need IL-15 to differentiate & activate



Ba2+: Barium ion



BabA: Blood group antigen-binding adhesion



BACE1: β-Secretase; Enzyme involved in the formation of the Alzheimer amyloidogenic peptide



BACH-1: A transcription represser; a sensor and effector of haem, regulating the HO-1 & globin genes



BACK-FUSION: Term for intra-luminal vesicles within endosome fusing back into the limiting membrane, releasing contents into the cytoplasm outside
the endosome



BACTERIOCHLORIN: A molecule with a large heterocyclic ring; similar to porphyrin and chlorin. See sensitizer



Bad: Bcl-2 antagonist of cell death; BH3-only sensitizer/de-repressor member of Bcl-2 family: pro-apoptotic



BAEC: Bovine aorta endothelial cell: lacks Na+/Ca2+ exchanger



BAF: Bafilomycin; an inhibitor of vacuolar ATPase



BAFF: (=BLyS) B cell-activating factor from the TNF family. Activates the alternative pathway of NF-κB. It is a type II transmembrane protein, but can be secreted as a soluble trimeric or polymeric form after cleavage from the cell membrane. BAFF & APRIL are expressed by monocytes, macrophages and dendritic cells, B lymphomas and to a lesser extent, by T cells. Other cell types also produce: airway, salivary, fibroblast-like synoviocytes, astrocytes, stromal bone marrow cells, and osteoclasts. IFNα, IFNγ, IL-10, G-CSF & CD40L, lipopolysaccharide & peptidoglycans can activate BAFF/APRIL from monocytes, macrophages & dendritic cells. BAFF binds particularly to BAFF-R and shares TACI & BCMA with APRIL. It plays an important role in B cell self-tolerance: a combination of low levels of BAFF and limited sensitivity of potential self-reacting cells, results in a failure to mature: over-expression results in auto-immune phenomena. Clinical studies have shown high levels in target organs for auto-immune diseases. Antagonists deplete mature follicular and MZ B cells and activated and memory T cells (which may act as APC for T cells), but left T1 immature B cells unaffected.



BAFF-R: (=BR3 & TNFRSF13c) BAFF receptor; expressed on B cells, also activated and memory T cells. Activates an alternative nuclear factor NF-κB2 pathway, including the nuclear translocation of p52/Rel B heterodimers: prevents the proteosomal degradation of the serine/threonine kinase NIK. It is a weak activator of the classical NF-κB pathway in B cells; NIK may also be involved. Through Akt, glycolytic enzymes are up-regulated. It may be induced by chromatin-containing immune complexes using a pathway independent of TLRs



BAFILOMYCIN A1: From Streptomyces griseus. Specific inhibitor of the V-type H+-ATPase responsible for acidification of endosomes. Levels used
to inhibit activity in DCs & macrophages are toxic for B cells



Bak: Bcl-2 antagonist killer-1. Pro-apoptotic effector factor of the Bcl-2 family. Associated with mitochondria and, when activated, causes mitochondrial
permeability, releasing Cytochrome-c



BAL: Bronchio-alveolar lavage; the collection of inflammatory or other cells from the bronchial tree by bronchoscopy and lavage



BALF: Broncho-alveolar lavage fluid



BAM32: Small cytoplasmic adapter protein associated with BCR signalling to actin in the lipid raft



BAMBI: BMP and activin membrane bound inhibitor; TLR4 suppresses it, enhancing TGF-β signalling during hepatic stellate cell activation



β-AMYLOID: An aggregating peptide of 40/42 aa; a major component of neuritic plaques in AD. Aa25-35 (not the reverse order) also forms fibrils and is toxic, like the full length peptide. Seems to block glycolysis to pyruvate, and mitochondrial function, with the release of ROS possibly from NADPH action. The ROS may consume GSH in nursemaid astrocytes, exposing neurons to oxidative stress. Glucolysis to lactate seems unaffected, not easily explained without a second, separate pathway.



BAND 3: The anion channel of erythrocytes; 379 aa; 1,200,000 monomers/RBC membrane. It has an acidic N-terminal end, which may bind GAPDH by inserting in the tetramer hole (1:1). It binds GAPDH (residues 1-11, 12-12), Aldolase (residues 1-23) and PFK (residues 12-23), inactivating each in doing so. Kidney band 3 has fewer residues at the N-terminal end (66-379 aa). LDH & PK do not bind directly to Band 3, so that their association in complexes probably involve other factors.



βAPP: β-Amyloid precursor protein; from which splits off β/A4, which is found in the senile plaques of Alzheimer's disease



BAPTA: 1,2-bis(2-Aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetrapotassium salt. It has x 2 (-N[-COOH]2). See BAPTA-AM



BAPTA-AM: 1,2-bis(2-Aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetrakis(acetoxymethyl ester). Selective chelator of intracellular Calcium stores. Membrane permeable form of BAPTA. It blocks the Calcium oscillations typically seen after sperm penetration of an ovum and blocks protein synthesis, which may, in part, explain the blocking effect on development



BAR: (a) Bin, amphiphysin, Rvs; domains that induce membrane curvature as for endocytosis

(b) β-catenin-mediated transcription reporter



β-ARB: β-Adrenergic RNA-binding protein



BARDET-BIEDL SYNDROME: A condition with may manifestations caused by defective ciliogenesis



BARIUM: Metal, Atomic weight (12C) 137.34, Atomic radium = 2.1 Å. Salts are used in some studies of Ca2+ channels because the Ba2+ ion moves
more freely



β-ARK: β-adrenergic receptor kinase



β-ARRESTIN: Associates with G-proteins; uncouples GPCR for internalization; binds to AP-2 . See Arrestin



BAR-DOMAIN: Bin/amphiphysin/Rvs homology domain; implicated in sensing and induction of membrane curvature



BARS-50: BFA-induced ADP-ribosylated substrate 50 kDa. See CtBP3



BASAL BODIES (of cilia): Have same basic structure as centrioles and are believed to be derived from them. Presumably, the unit providing periodic
motion. Together with cilia, may form the biochemical bases for a number of sensory organs (olfactory, hearing, position)



BASC: Large complex that contains ATM, the Nbs-MRE11-RAD50 complex, mismatch proteins (MSH2/6 and MLH2) and the Bloom's helicase. Each
can recognize aberrant DNA



BASCs: Broncho-alveolar stem cells; the putative precursor for bronchial adenocarcinoma



BASEMENT MEMBRANE: A thin extracellular layer found in normal tissues which lies adjacent to the basal surfaces or external surfaces of epithelial, endothelial and other cells. It can be identified by light microscopy and is highlighted by the PAS stain. The main constituents are laminin-111, collagen-IV, heparan sulphate proteoglycan, entactin/nidogen and sequestered growth factors (FGF, TGF-β, EGF etc.). Cancer cells can degrade the integrity of the basement membrane and metastasize



BASH: See SLP65



basicFGF (bFGF): = FGF-2



BASIGIN: See EMMPRIN (also GP-70) & CD147



BASONUCLIN: A zinc finger protein, generally found in stratified epithelium keratinocytes and in centrosomes of developing spermatids



BASSOON: Large (420 kDa) proteins in the CAZ. Related to Piccolo/aczonin, with 10 shared PBH domains (Piccolo-Bassoon-Homology). Both only in vertebrates. Bassoon is post-translationally modified by myristoylation. Both interact through their third CC domain with ELKS & CtBP. Knockout mice lack ability for ribbons to attach to the arciform layer of the CAZ.



BATHOPHENANTHROLINE: Used for iron determinations. Binds to metal ions



Bax: Bcl-2 associated x protein. BH3 member of Bcl-2 family: pro-apoptotic effector. Associated with mitochondria and, when activated (Bax-NT), causes
mitochondrial permeability, releasing Cytochrome-c; associates with 14-3-3 protein which may act as chaperone; the Ku70 protein binds the N-terminal and blocks relocation to the mitochondria; in T-lymphocytes with STS, the maximum cytoplasmic staining level occurred at ~20 min, with AIF appearing at ~30 min



BAY K 8644: An agonist of voltage-dependent Ca2+ channels (VDCC); can inhibit autophagy



BAY 11-7082: A NF-κB inhibitor



BAY 58-2667: A guanylate cyclase inhibitor; protects from endotoxic shock



BAZOOKA: A component of the Par protein complex for apical polarity with Bazooka/Par3, Par6 & aPKC; See Par 3



Bb: Borrelia burgdorferi; the organism responsible for (true) Lyme Disease in the USA (cf Lyme syndrome)



BB1: See B7



41BB: Receptor of the TNFR family



BBB: Blood-brain barrier



BBB Locomotor Rating Scale: From Basso, Beattie & Bresnahan; 21 points, generally ordinal



BBC3: Gene for PUMA



BB LOOP: Motifs in certain TLRs; used for homodimerization (eg TLT4 & TLT10)



BBM: Brush border membrane



BBS4: A centriolar satellite protein, involved in the Bardet-Biedl syndrome; a linker protein between PCM1 and p150glued



BBS6: involved in cytokinesis



β-BUNGAROTOXIN: From Bungarus multicinctus; Phospholipase A2; destroys synaptic vesicles and inhibits acetyl choline release



BCA-1: B cell-attracting chemokine = CXCL13. BCA-1 and SDF-1 are important chemokines in the formation of germinal centres in lymphoid tissue, especially in inflamed tissues, such as the synovium of rheumatoid arthritis and the peri-ductal collections in Sjögren's syndrome. In ectopic lymphoid sites in Sjögren's syndrome, BCA-1 is found in the endothelial cells of venules, as well as in the germinal centres.



B-CAM: Basal cell adhesion molecule; a truncated form of Lutheran glycoprotein; a laminin-511 receptor



β-Catenin: A gene promoter of 92 kDa, normally kept inactive within the cytoplasm complex of Axin, adenomatous polyposis coli, GSK-3 and Dishevelled. Has multifunction; involved with cadherin-mediated cell adhesion and the Wnt pathway. GSK3 targets β-Catenin for phosphorylation, ubiquitination and proteasome elimination. In the canonical pathway, β-catenin, on arriving within the nucleus can associate with p300 or CBP (competitive), the former being required for would repair. Up-regulation marks the stem cell for CML. It is a co-activator and regulator of a number of nuclear receptors, particularly androgen receptor, probably based upon structural features. It promotes the up-regulation of a number of MMPs; genes targeted are - for cancer proliferation (c-myc, cyclin D1), invasion (MMP-7 & MT1-MMP) & angiogenesis (VEGF); there appears cross-talk between β-catenin & NF-κB whereby, by association in the cytoplasm, one can decrease the effectiveness of the other in the nucleus with respect to gene activity & function



BCE: Bovine corneal epithelium



BCECF-AM: 2',7'-Bis(2-Carboxyethyl)-5-(and-6)-carboxy fluorescein acetoxymethyl ester; a fluorescent, pH-sensitive dye, used for measuring
intracellular pH



B CELLS: Antibody-producing, derived in early foetal life in the liver, but later from bone marrow in Mammals. They are seeded to the lymph nodes and spleen, but last only a few days unless stimulated. Each has ~105 identical Ig TCR receptors per cell, with an antibody-combining site 7-8 nm2. Peptides 8-10 aa long are presented typically by MHC Class I molecules on APCs. The marrow has no positive selection, but those with sub-reactive H & L chains do not proceed. Negative selection is not known. The V gene of B cells (not T cells) engage in somatic hypermutation after antigenic mutation, probably as a transition to memory B cells in germinal centres. The mutation rate ~10-3 (base pair)-1 generation-1, with the occasional mutant with higher affinity that may be selected with subsequent Ag. There are two subsets, B-1 & B-2; the antigenic range of B-1 is limited (peritoneum & body cavities), that for B-2, diverse (lymph nodes, blood & spleen)



β-CELLS (of Pancreatic islets): Secretes insulin. Apoptosis is induced by high doses of glucose and sulphonylurea; implicated are IL-1β, IFN-γ, TNF-α
and Caspase 3.



BCG: Bacillus Calmette Guerin (From Mycobacterium bovis). The anti-tumour immune effects are attributable to antibodies generated by the bacterial DNA



Bcl-2: Chromosome 18. Oncogene that is anti-apoptotic. It is frequently translocated to Chromosome 14 in follicular lymphomas



Bcl-2 (family): B cell CLL/Lymphoma-2. Bcl-2 oncogene product; an inhibitor of Caspases, including all mitochondrial apoptogenic activity in vertebrates; function in Drosophila is unclear; inhibited by the BH3 members of the family by forming heterodimers which neutralize it. Bcl-2 blocks Fas-induced apoptosis and causes GSH to enter nucleus and block apoptosis - may block Caspases [homologous to IL-1beta converting enzyme (cysteine protease)]. Bcl-2 expression causes redistribution of glutathione to the nucleus, reduces Ca2+ stores (ER) and reduces Ca2+ intake; inhibits BECN1 in the ER, but not in the mitochondria; identified in follicular B cell lymphoma by a translocation to the heavy chain immunoglobulin locus (t(14:18) becoming constitutively hyper-expressed

Bcl-G: Two isoforms exist in humans (one in mice); binds weakly to some of the Bcl-2 family; seems to bind to proteins of the transport particle protein complex and does not appear to be involved in apoptosis pathways

Bcl2L1: Bcl-XL



Bcl2L2: Bcl-W



Bcl2L11: Gene for BIM

Bcl2L11: BIM; interacts with Dynein light chain, from which it can be released, an initiate apoptosis by activating Bax/Bak1; also interacts with Beclin 1, facilitated by DYNLL1 & Bim; by linking Bim, DYNLL1 & Becn1 to microtubules, autophagy is inhibited; phosphorylation of Bim by JNK and the interactions are broken-up



Bcl-6: A marker of germinal centre origin; a transcriptional repressor required for germinal centre formation; JAB1 is necessary for its expression



B-CLL: B-cell chronic lymphocytic leukaemia



Bcl-XL: Truncated member of Bcl-2 family - like Bcl-2



B104CM: A neuroblastoma-conditioned culture medium used for rat OPC culture. It contains PDGFAA and neuregulin 1. Mice need additional cAMP



BCMA: (=TNFRSF17) B-cell maturation antigen, a member of the TNFR family; expressed on plasma cells, plasmablasts and tonsillar germinal centre
B cells, activated T cells and regulatory T cells. Activates NF-κB, Jnk, Elk-1 & p38 kinase



BCNU: N,N'-bis(2-chloroethyl)-N-nitrosourea; an inhibitor of glutathione reductase; increases the sensitivity of some cells to oxidative stress



β-COAT PROTEIN: protein (-COP). See Protein Kinase C



β-COP: β-COAT Protein; a marker for Golgi membranes



BCR: B-cell receptor; sIgM, CD79a, CD79b. A multi-subunit complex of membrane-bound immunoglobulin molecule and the transducing signal heterodimer Igα/β; upon BCR activation, tyrosine-based ITEMs (x2) in the heterodimer are phosphorylated by the protein kinases Lyn (~1 ITEM) & Syk (2 ITEMs). The adapter protein SLP-65 (= BLNK or BASH) is recruited and phosphorylated by Syk also, and activates downstream cascades as well as exerting an allosteric regulation on upstream Syk



Bcr-Abl: (Breakpoint cluster region.) The abnormal genetic result of the Philadelphia chromosome. Bcr encodes an 160 kDa protein of unknown function. It
has some homology with n-Chimaerin protein; the protein kinase targeted by Imatinib



Bcr-Abl kinase: product of Bcr-Abl - an abnormal tyrosine kinase which promotes proliferation of granulocytes in Chronic Myeloid Leukaemia. Inhibited
by Imatinib



BCRP: Breast cancer resistance protein; the members of this ABC subfamily are ~half the size of the full-length ABC transporters; known as 'half-transporters'; See ABCG2



BCX-1777: Inhibitor of the enzyme PNP



BD1047: N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-2(dimethylamino)ethylamine; sigma-1 receptor antagonist



BD1063: 1-[2-(3,4-dichlorophenyl)ethyl]-4-methylpiperazine; Sigma-1 antagonist



BDK: Bradykinin



BDNF: Brain-derived neurotrophic factor; binds to TrkB. It binds with GAGs, forming a large complex which can bind to TrkB and p75 Neurotrophic
receptor; the GAGs may hold BDNF in reserve and regulate its release; signals through p75NTF



BEC: Bioenergetic cellular index; an expression of mitochondrial metabolic enzyme activities



BECLIN-1: A BH3-only pro-autophagic protein, ~55 kDa; a key regulator of autophagy, binding (N-terminal BH3) the suppressor domains of IP3R1 & R3 and sensitizing them; dimerizes and combines with many proteins, including Vps34, Vps15, UVRAG, Ambra1 & Bif1 to form the PtdIns3K complex III for the formation of autophagosomes. Beclin-1 is essential for the function of this complex. The BH3 domain can combine with Bcl-2, BclxL Bcl-w, which can inactivate it.



BECKWITH-WIEDERMANN SYNDROME: (=EMG Syndrome) Defect with Chromosome 11p15; large tongue and viscera, umbilical hernia and abdominal wall defects, metopic ridge, fits, perinatal hypoglycaemia and increased incidence of tumours - Wilm's, adrenal carcinomas etc. Mental function mildly decreased. May be associated with prolonged embryo cell culture in vitro and epigenetic imprint



BECN1: Beclin-1; binds to, and is inhibited by Bcl-2, Bcl-XL, Bcl-W & MCL1



BECN1 COMPLEX: A complex that includes BECN1, PI3K class 3, Vps34, Vps15 & AMBRA1;



BELIMUMAB: A monoclonal antibody against human BAFF. Experimental



BEPHRIN: A transmembrane receptor



β-ELIMINATION: The degradation of glycosaminoglycans using Sodium borohydride (NaBH4) in an alkali solution. The core proteoglycan is split off.



BENNETT's REAGENT: 1-(4-chloromercuriphenylazo)-2-naphthol; Mercury orange; a stain for -SH groups. Usually dissolved in ethanol (80%) or
butanol solution.



BENZONASE (Trade mark): Enzyme from Serratia marcescens, expressed in E coli for production. Digests native or heat-denatured DNA & RNA



BER: Base excision repair (of chromosomal DNA)



BERBAMINE: An extract from Berberis amurensis; reported to have an anti-leukaemia action (CML), with inhibition of p65 NF-κB movement and activation of Caspase-3; may have potent anti-inflammatory actions



BERBERINE: Treatment slows the proliferation of ADPKD cystic cells



Ber-H2: See CD30



BETACELLULIN: An heparin-binding EGF-related cytokine, 80 residue glycoprotein.



BETAGLYCAN: A minor HSPG; the heparan sulphate chain is not necessary for the function of the core protein as a co-receptor for TGF-β



BF: Bathophenanthroline; used for iron determinations



BFA: Brefeldin A; a fungal product that inhibits membrane transport, and particularly affects the Golgi



β-F1-ATPase: H+ATP synthase; a rate-limiting component of mitochondrial oxidative phosphorylation. May be repressed in cancers, but an elevated
level may indicate a worse prognosis



bFGF: Basic fibroblast growth factor



BFU: Burst colony-forming units (eg BFU-E [-erythroid])

BFU-E: Erythroid progenitors, considered more immature than the CFU-E



B4GalT1: A marker for the trans-Golgi structures



β-Gal: β-Galactosidase



β2GPI: Apolipoprotein H



Bgr1: Involved in inducible nucleosome modelling, brought to promoters after an initial exposure to increase responses



BH1-4: Bcl-2 homology 1-4; those with all four are anti-apoptotic and generally associate with the OMM (also ER & cytosol)



BH3 PEPTIDE: The minimal unit of BH3-only protein function



BH3only: Bcl-2 homology 3 only; Pro-apoptotic; BAK, BAX & (BOK)



BHA: Butylated hydroxyanisole; ROS scavenger; reduces TNF-induced necroptosis at a point below RIPK1



β-HEXOSAMINIDASE: A lysosomal enzyme; released into the medium by exocytosis when the lysosomes are involved in the membrane repair response (see HexB)



BHK: Baby hamster kidney cells



bHLH: Basic helix loop helix proteins, involved in gene regulation during differentiation. The basic component binds to DNA, the rest is involved
in dimerization.

Class I or E-box binding proteins or E proteins; eg HEB E2A da. These are major factors in lymphoid differentiation. E12 E 47 E2-2 & HEB bind to CANNTG in DNA and inhibit or activate gene expression. E12 & E47 are splice variants of a single gene Tcfe2a. DN3 thymocyte pre-TCR signals suppress E-protein expression, allow progression to DP with several rounds of cell division: E47 regulates the accessibility of the TCR Vβ loci. Loss of E protein activity results in CD8+ SP thymocytes

Class II eg MyoD, Myf5, MASH, HASH, TALI

Class III eg c-Myc, TFE3; contains a zip domain

Class IV eg Mad Max

Class V eg Id, emc

Class VI Have a Pro residue in the basic region; HES-1

Class VII eg AHR, has PAS domain



BHMT: Betaine:Homocysteine methyltransferase, 45 kDa



BHQ: 2,5-di-tert-butyl-1,4-benzohydroquinone; inhibitor of SERC activity



BHT: Butylated hydroxyl toluene; an antioxidant



BI-1: Bax inhibitor, ER localized



BICALUTAMIDE: An androgen antagonist



BICINE: N,N-bis(2-hydroxyethyl)glycine



Bid: Bcl-2 interacting domain death antagonist, p21, cytosolic → mitochondrial; sensitizer/de-repressor BH3-only member of Bcl-2 family: pro-apoptotic; cleaves to the active tBid, p15, at the commencement of caspase activation



BIGLYCAN: Chondroitin/dermatan sulphate proteoglycan



βIG-M1 & 2: See CCN1 & 2



Bik: Bcl-2-interacting killer; sensitizer/de-repressor BH3-only member of Bcl-2 family: pro-apoptotic



BIKUNIN: A simple proteoglycan has a single glycosaminoglycan chain with a broad-spectrum inhibitory activity against serine proteases; recombinant
human bikunin has MW of 25 kDa and would appear to have a defined sequence



BILAYER: Refers to the typical membrane forming the plasma membrane and certain cellular organelles, in which there are two layers of phospholipids; phosphatidylserine is found in the inner leaflet of the plasma membrane; its location there can change with reactions to stresses, such as intracellular Ca2+ rise and apoptosis signals, and appear on the external leaflet. There, it may activate macrophages and clotting factors. The shift may involve lipid rafts, SOCE, MAPK pathway

Bim: Bcl-2 interacting mediator of cell death; sensitizer/de-repressor BH3-only member of Bcl-2 family: pro-apoptotic



BIM: Bis-indolylmaleimide; PKC modulator by competing for ATP at the latter's catalytic site. (It is fluorescent)



BimEL: A major splice variant of Bim (see Bim); is phosphorylated by Aurora A kinase early in mitosis and dephosphorylated by protein phosphatase 2A (PP2A) at the exit from mitosis



β1-Integrin: One chain of usually a heterodimer found at the cell surface and involved in cell-to-cell adhesion. Alone, it is used as an indicator of stem cell status



BIO: 6-Bromoindirubin-3'-oxime - a relatively specific inhibitor of GSK-3; derived from the Mollusc 'Tyrian purple'. It is more specific than Lithium, but
not as specific as CHIR99021, affecting other kinases



BioGEE: Biotinylated glutathione ethyl ester; can be used as a maker for oxidant-induced S-Glutathiolation; it is plasma-membrane permeable but become
trapped by the actions of cellular esterases



BIOGLYCAN: A small, leucine-rich proteoglycan have chondroitin sulphate with some IdoA modification, making it a Dermatan; prominent in blood
vessels



BIOLOGICS: Parenterally administered protein therapeutics



BiP: (GRP78) A member of the HSP70 family (~65% homology) chaperone and an ATPase, located in the ER and binds Ca2+, promotes folding of hydrophobic regions of polypeptides, but which de-localizes to the nucleus and plasma membrane when there is stress. It is an autoimmune antigen found in Rheumatoid arthritis, and is targeted by both T & B cells



BIR: Baculoviral IAP repeat; inhibition of apoptosis protein repeat domain



BIRBECK GRANULES: Found in Langerhans cells



BIRINAPANT: A bivalent Smac mimetic; targets TRAF2-associated cIAPs



BIS: Bisindolylmaleimide 1; PKC inhibitor



BISBENZIMIDE H: Fluorescent dye (blue) used to stain nuclei; membrane permeable with low toxicity. Identifies the A-T regions of DNA



BISINDOLYLMALEIMIDE 1: A potent and selective inhibitor of PKC



BIS(ACETYLGLYCERO)PHOSPHATE: A lysosomal lipid



BISPHOSPHONATES: Synthetic analogues of pyrophosphate; potent inhibitors of bone resorption through inhibition of osteoclasts. Inhibit the transcription
of GAPDH



BISULPHITE: Used for deamination of cytosine residues in DNA



BIX01294: A G9a inhibitor



BJAB: A transfectable, mature human B-cell line



BK: (a) Bradykinin; causes a rapid rise in IP3 in endothelial cells, falling after ~5 min

(b) BK polyoma virus; a problem in renal transplantation units, arising from re-activation and causing a nephropathy



BL34: Activation gene for mitogen-activated B cells



BL60: Burkitt's lymphoma cell line, EBV+



BLADES (of centriole): Usually made of triplets of microtubules (A,B and C), forming the wall of the cylindrical centriole (Generally only A & B in basal bodies of cilia). The number of tubules per blade in centrioles may reduce to 2 distally, more closely resembling the basal body. Associated with/contain alpha, beta and gamma tubulin, Sp77, Sp83, Rib43 and Tektins



BLASTOCYST: Stage in embryonal development, when there is formation of the blastocoele. This fills with fluid, the ions Na+ and Cl- actively moved
with a Na/K-ATPase



BLASTOMERE: Product of division by the zygote. The inner progeny form pluriblasts, the peripheral cells form polaroblasts



BLAU SYNDROME: A dominant, inherited granulomatous disorder of childhood with strong similarities with sarcoidosis.



BLC: B lymphocyte chemoattactant



Bld2: Chlamydomonas mutant which results in thin rings of singlet microtubules in the centriole and cytokinesis defects.



BLD-10: Component of the centriole cartwheel



BLEB: A microscopic blister-like membrane bulge; a feature of apoptosis, indicating rearrangement of the membrane phospholipids



BLEOMYCIN: A chemotherapeutic drug of long standing, but had appreciable side effects. Recently it is more popular for use in electroporation
techniques because of better intracellular access



BLEPHOROPLAST: A centrosomal-like organelle of lower plants



BLI: Bioluminescent imaging



Blimp-1: Marker for murine sweat gland stem cells



BLINaC: Brain, liver, intestine sodium channel; also found in kidney & lung; function is not clear; rat rBLINaC is inhibited by Ca2+, whereas mouse mBLINaC is constitutively open; a single amino acid may make all the difference



BLM: Gene for Bloom's syndrome - See Helicase



BLM: Bloom's helicase



BLNK: (SLP65) B-cell linker protein; an adapter protein involved in CD20/BCR Ca2+ channel signalling (See Slp-65)



BLOC-1: Biogenesis of Lysosome-related Organelles Complex -1; essential for melanosome biogenesis & other conditions



BLOOD ISLAND: Term for a unit of definitive erythropoiesis in the liver and bone marrow, with a macrophage surrounded by developing erythroid
cells of different ages; the macrophage supplying cytokines +/- scaffold



BLOOM'S SYNDROME: See Helicase. Proportional dwarfism, telangiectatic erythema, immune deficiency and an enhanced risk (x100) of most cancers (mean age 25 y). There is pairing between homologous chromosomes and large numbers of sister chromatid exchanges and micronuclei, expelled in S phase, reflecting failed DNA replication events. There is increased somatic mutation, with loss of heterozygocity



BLOT: Techniques transferring material to be analysed from one medium to another by blotting : examples

Northern Blot: RNA is separated by electrophoresis in a gel. (All) the separated fractions are transferred by blotting to another medium (eg nitrocellulose membrane) and exposed to cDNA or mRNA probes (fragments), the bound fractions then being identified by a detection process (eg autoradiography)

Southern Blot: DNA is fragmented and then subjected to electrophoretic separation. Labelled RNA on a separate medium is applied (blotted) onto the former medium, allowed to combine, then subjected to a detection process (eg autoradiography)

Western Blot: Proteins are separated by electrophoresis in a gel. (All) the separated fractions are transferred by blotting to another medium (eg nitrocellulose), where they are subjected to some selective detection process (eg antibody precipitation & protein staining)



BLP: Bacterial lipoprotein



BLyS: See BAFF



BM: Bone marrow; haematopoietic cells, stroma, capillaries & venules, extracellular matrix and fat



BMD: Bone mineral density



BMDM: Bone marrow-derived macrophage



β-MERCAPTOETHANOL: A thiol donor; enhances GSH content in PC12 cells & counters Cumene hydroperoxide toxicity



BMF: Bone marrow failure



BMG: Bone marrow graft



Bmi-1: A Polycomb Group (ring finger) oncogene required for self-renewal and proliferation of normal and leukaemic haematopoietic stem cells



β2-MICROGLOBULIN: It is a 12 kDa membrane glycoprotein of mammalian nucleated cells; a structural part of the MHC Class I molecule.



BMK/ERK: Big mitogen-activated protein kinase/extracellular signal-regulated kinase



BmN4: Silkworm ovary cells; good for studying germ-line piRNA



BMNC: Bone marrow nucleated cells



BMOC: Brinster's medium for ovum culture



Bmp7: Gene (mouse) for Bone morphogenic protein 7



BMP: (a) Bone morphogenic protein; contrary to the implication in its name, it is inhibitory, blocking stimulation, embryonic differentiation, invasion,
migration and proliferation of osteoblastic tumour cells, esp. BMP-2, -6 & -7. It requires heparan as a co-receptor, and is itself, inhibited by Notch. Bmp-4 acts on murine ESC with LIF via the Smad-mediated induction of Id and inhibition of p38 MAPK; Bmp-7 stimulates sprouting from the embryonal central foregut endoderm and is essential for hepatic cell differentiation; also found in inflamed fibrotic livers; Bmp-7 signalling is countered by follistatin, noggin and members of the DAN family (eg cerebus & gremlin)

BMP-2: Marker for visceral endoderm

(b) Bis(molacylglycero)phosphate = lysobisphosphatidic acid



BMS-345541: (N-(1,8-dimethylimidazo(1,2-a)quinoxalin-4-yl)-1,2-ethanediamine hydrochloride); inhibits IκB-kinaseβ



BMT: Bone marrow transplant



BMV: Brome (annual grasses) mosaic virus. Used as a standard in electrophoresis



BMX: Bone marrow tyrosine kinase in chromosome X; associates with TNFR2; seems to play a part in the tissue response to ischaemia & angiogenic remodelling, being critical for migration & tube formation; activates RhoA, not Rac1 or CD42



β-N-Acetylhexosaminidase: A 'classical' marker for lysosomes



β-NF: β-Naphthoflavone; a non-genotoxic agonist of AhR



BNIP3: Bcl2/adenovirus E1B 19 kDa interacting protein-3. It is involved in apoptosis, and is over-expressed in many cancers. It has been considered to be
pro- cell death, it acts also as a transcription co-repressor of the apoptosis inducing factor gene
AIF. Transcription of BNIP3 is regulated by HIF-1α



BNP: B-type natriuretic peptide



BOC-D-fmk: General Caspase inhibitor



BODIPY: Boron dipyrromethene difluoride; bright fluorescent compounds used for labelling; when used to label short chain fatty acids, the fluorescence
spectrum changes with concentration



BOK: (MTD in humans) Protein has aa sequence similarities with Bax & Bak; expressed particularly in cells of the female reproductive system; function unclear, but may have a pro-apoptotic function; the genomic region encoding for Bok is frequently absent in human cancer; the C-terminal end forms a tail which anchors the molecule to the ER & Golgi; may induce apoptosis in a Bax/Bak-dependent manner



BOMBAY BLOOD GROUP: Blood group H lacking fucose



BONFERRONI CORRECTION: Correcting the probability for significance when multiple assessments are made upon one set of data



Boo/Diva: A Murine ovary-specific member of the Bcl-2 family. The human orthologue is expressed in ovary, liver and kidney, chromosome 15q21 (relevant to cervical cancer); translocates to the mitochondria by vincristine; over-expression is lethal



BORRELIA BURGDORFERI: The causative organism of Lyme Disease, described in North America; a multi-system disease with an acute phase that may lead on to a chronic phase which may or may not have detectable organisms. Similar conditions in other countries, which may be caused by a variety of similar or different organisms, may best be termed Lyme Syndrome



BORTEZOMIB: Inhibitor of ubiquitin-mediated proteasome degradation; it may be helpful as treatment of relapsed multiple myeloma, especially in those
with renal failure, because it is not excreted via the kidneys



BOSE-EINSTEIN CONDENSATES: Groups of atoms or molecules can be brought into a quantum coherent state in which they surrender individual identity
and behave like one quantum system, with all components 'feeling' any perturbation



botv: Brother of tout velu (Drosophila)



BOVINE SERUM ALBUMIN: An active inhibitor of spermatozoon lipid peroxidation



bp: Base pairs (nucleotides)



BP: Benzo[a]pyrene; carcinogenic compound, representative of a group; metabolism is initiated by cytochrome P450-dependent monoxygenases (CYPs)



BP-1: A cell surface amino-peptidase, expressed during the IL-7 responsive phase of B cell development



53BP1: Protein that binds p53. Attracted to sites of DNA DSBs. Checkpoint mediator, able to interact with post-translationary modified histones. See Mdc1



BP3: Stromal cell marker



BPA: Bisphenol A; (CH3)2C(C6H4OH)2; an ubiquitous component of plastics and epoxy resins; it is considered to disrupt oestrogen and thyroid hormone function; considered to play a part in human prostate cancer causations, possibly by interfering with microtubule enucleation and centrosomal function; however, it may reduce the PSA levels in those with prostate cancer

BPAG1: A major plakin protein



BPDE: (+)-anti-BP-7,8-diol-9,10-epoxide; metabolite of BP & potent carcinogen; triggers formation of bulky DNA adducts and subsequent mutations



BPE: Bovine pituitary extract



β-PE: β-Phorbol ester



2,3-BPG: 2,3-Bisphosphoglycerate. Found at high levels in RBCs



BPNT1 (= [rat] RnPIP, 308 aa & 33.2 kDa [rat]): Bisphosphate 3'-nucleotidase; a cytoplasmic family of 7 enzymes that are inhibited by Lithium; four of these are -

BPNT1: Expressed in liver, kidneys, pancreas, brain, spleen, testis, skeletal muscle & heart; has inositol polyphosphate-1 phosphatase activity; is sensitive to Lithium & Ca2+ inhibition; Ki (Li) ~0.8 mmol/L

INPP1: Inositol polyphosphate 1-phosphatase

FBP: Fructose-1,6-bisphosphatase 1 & 2

IMP: Myo-inositol monophosphatase A1 & A2

Intra-Golgi -

gPAPP: Converts PAP to 5'-AMP; see gPAPP





BP1-PE: Marker for murine thymic cortical epithelial cells



BQR: Brequinar



BRI & II: BMP receptor I & II



Brachyury: T-box transcription factor:



BRADFORD REAGENT: See Coomassie Blue



BRADYKININ: A phosphoinoside agonist that generates IP3; a potent endothelial-dependent vasodilator



BRAF: An oncogene, mutations (often producing BRAFV600E) enable colorectal cancer genesis, with adenomas > 1 cm



BRAF: Links with MAPK and inhibitors augment apoptosis; malignant melanomas can have an activating mutation that can be a target for therapy and Wnt/β-catenin can boost apoptosis



BRAK: CXCL14, from Chromosome 5; a chemo-attractant for monocytes and dendritic cells that may inhibit tumour growth.



BRCA1: Tumour suppressor gene for breast cancer



Brca1: May associate with microtubules. Part of a large complex BASC. Required for S phase and early G2 phase checkpoints (activated after DXRT). Is up-stream of other important DNA repair factors Brca2 and Rad51. The chromatin-bound fraction of Brca1 whose retention at the DBS site is controlled by Mdc1



BRCA2: Tumour suppressor gene for breast cancer



BRCP: Breast cancer resistance protein.



BRCT-repeat: Asparagine/Aspartate - Arginine - Cysteine - Threonine. Feature of a class of proteins that includes BRCA1 and the AMD of PARP-1



5-BrdU: 5-Bromo-2'deoxyuridine; Thymidine analogue, used as a mutagen in genetic research: selectively incorporated into cDNA during S phase.



BREAST CANCER: Currently divided into 6 clinically-relevant subtypes (molecular gene signatures):

"basal" - basal cell markers are high: cytokeratins 5,6 & 14

basal-like

CLBC

normal-like

"luminal" A & B - high luminal cell markers: ERα, GATA3, FoxA1 & cytokeratin 18

Other factors include grade, stage, hormonal and receptor (c-erbB2) status. Newer influences include Tpl2 & COX-2

Breast cancer stem cells tend to have the immunophenotype – CD44hi CD24lo & ALDHhi



BREFELDIN A: From Penicillium brefeldianum. It fragments the Golgi, is an activator of the sphingomyelin cycle and can mediate apoptosis in tumour cells



BREQUINAR: An inhibitor of dihydroorotate dehydrogenase; see DHODH



BRILLIANT BLUE G: P2X7 receptor inhibitor



BRIJ 58: Detergent, used for permeabilization of cells, and said not to disturb the microfilament arrangements, and is much less disruptive that
Triton X100. Glycolytic enzymes (particularly GAPDH & Aldolase) tend to remain attached to cytomatrix



Bro1: (BCK-like resistance to osmotic shock.) Monomeric protein intimately associated with the ESCRT complexes; involved in de-ubiquitination
and trafficking, recruiting Doa4



BROMOCRIPTINE: Dopamine D2 & D3 receptor antagonist



BROWN ALGAE: Possess centrioles that act as MTOCs (unlike land plants) and forms spindle poles as in animals. Cell plate formation and completion
of cytokinesis resembles that in and plants



3-BrPA: 3-Bromopyruvate. Blocks glycolysis and depletes ATP. Dephosphorylates BAD, leading to apoptosis. Is an alkylating agent, and not stable in solution



BRUCE: An IAP



BRUCHPILOT: A protein in Drosophila with homology with ELKS. Is essential for the organization of the CAZ & assembly of T-bar.



BRUCH'S MEMBRANE: A five-layered structure between the RPE and the choriocapillaris: the inner collagenous layer, the elastin layer, the outer
collagenous layer, and the basement membrane of the choriocapillaris. Probably largely produced by the RPE



BRUGADA SYNDROME: Polygenetic condition characterized by life-threatening cardiac arrhythmias and sudden death; there may be clusters of elevated and decreased serum proteins



BS: Brugada syndrome



BRYOSTATIN 1: A PKC modulator; causes initial activation and translocation to the plasma membrane, then disintegration from both plasma membrane
and cytosolic pools. Most activity is lost after 2 h, but with a 48 h recovery/washout



BSA: Bovine serum albumin; MW 68 kDa



BSC: Best supportive care (as may be given to control group members in a clinical trial)



BS-C-1: African green monkey kidney cell line



β-Secretase: BACE1



BSK-II: Barbour-Stoenner-Kelly medium; a selective culture medium for Borrelia burgdorferi spirochaetes



BSO: L-Buthionine sulphoximine; inhibitor of GCL



B-SOC: BCR-mediated store-operated Ca2+ entry; requires tyrosine kinase action and STIM1, independent of Orai



BST-1: See CD157



BT: Bos taurus; cow



BT-20: Human breast cancer cell line. Has some differentiation, and 1,25-(OH)2D3 induces up-regulation of GAPDH gene expression, with reduced
proliferation and expression of EGF-R



BTAK/STK15: A centrosomal kinase



BTC: Betacellulin



BTK: Bruton's tyrosine kinase; an effector for the G-protein receptor system; links with SLP65; phospholylates/activates PLC-γ2



BTLA: B & T lymphocyte attenuator: HVEM is ligand



BTP-2: A strong SOC inhibitor



β-TrCP: β-transducin repeat containing protein; Ubiquinates β-Catenin for proteasome destruction; Wnt signalling causes the dissociation from the Axin1/GSK-3β/Frizzled/(PDZ/RGS3 ?) complex



BTSC: Brain tumour stem cell. Express CD133+



BtuBD: Vitamin B12 transporter/importer



β-3-Tubulin: Marker for neural cells



BUB1β: Budding uninhibited by benzimidazole 1b; a mitotic check-point serine/threonine protein kinase; it is sensitive to peroxide



BUFALIN: A cardiotoxic steroid that can induce differentiation and apoptosis in tumour cells; derived from the Chinese toad venom Chansu, a galencial preparation of the dried white venom of the Chinese Bufo gargarizans with a MW of 386.5; thought to produce apoptosis of some cancer cell lines through the PI3K/Akt pathway, also via TRAIL, and suppress proliferation; prostate cancers may respond better than breast cancers and leukaemias may respond well



BUFODIENOLIDE: A group of compounds that include Bufalin, Bufotalin and Gamabufotalin; See under Bufalin



BUFOTALIN: A Bufodienolide; see under Bufalin



BURKITT LYMPHOMA: Tends to occur in a nasopharyngeal distribution and is associated with a maturation arrest of centroblasts.



BUTHIOMINE SULPHOXIMINE: An inhibitor of Glutathione synthesis



BUTYRATE: Inhibits Histone deacetylase: induces hyper-acetylation of core histones and the access of transcription factors to the chromosomal DNA.
It does not stimulate transcription promoters



BUTYROLACTONE I: Inhibitor of Cdk2



BV6: A Smac mimetic; may act through DR5 and stimulate NF-κB



BWW: Biggers-Whitten-Whittingham medium for embryo culture



β-XYLOSIDE: p-nitrophenyl-β-D-xylopyranoside. Competes out the GAG chain synthesis for the core protein of an HSPG



BZ-423: 1,4-Benzodiazepine; extends the rise in cytosolic Ca2+ after BCR ligation



bZIP: Family of gene transcription proteins (eg c-Maf)



C: Constant (as relates to antigen-receptor genes for immunoglobulins)



C1(-n) Domain: Cytoplasmic domain loop of a molecule which has multiple passages through a membrane. Loop may be 'sandwich' - like rabbit's
ears (eg C2A&B)



C6: A rat malignant glioma cell line. When implanted into rat brains, the behaviour is considered quite similar to that of malignant gliomata in humans



C83: A proteolytic product from APP



C99: A proteolytic product from APP



C1q: Early component of the Complement pathway. Deficiency is associated with infections; knockout shows SLE-like features and lupus nephritis,
with inefficient clearance of apoptotic bodies



C2 Domains (synaptic proteins): Are characterized as Ca 2+/phospholipid-binding modules



ca.: About, in the vicinity of, or approximately [Latin: circa]



Ca: Carcinoma/cancer



CA: Carbonic anhydrase; some involved in attempts to maintain the pHi within physiological limits; are metalloenzymes that convert the carbon dioxide from oxidative metabolism plus water to bicarbonate and protons (or the reverse):

CA2

CA9, (CAIX): Transmembrane and involved in tumour progression & metastasis; HIF1α targets CAIX upregulation in hypoxic regions

CA12, (CAXII): Transmembrane and involved in tumour progression & metastasis



cA2: Infliximab



CA-4: Combretastatin A-4; a chemotherapeutic agent



CA19-9: A monoclonal antibody directed against the sLea structure and used as a tumour marker, particularly for pancreatic cancer; it can give false positives



CA074 Me: An inhibitor of cathepsin B



CAA: Cerebral amyloid angiopathy; a feature of Alzheimer's disease, in which there is degeneration of vascular smooth muscle cells close to the
regions of the basement membrane where amyloid protein builds-up



cABC: Chondroitinase ABC



CACO-2: Human colon adenocarcinoma cell line



C3bi: Opsonin present on apoptotic cells. (Receptors are CD11b/CD18 & CD11c/CD18). It seems to play an important role in tolerance induction



c-ABL: Gene sequence on Chromosome 9 that is moved adjacent to the BCR gene in Chromosome 22 to form the Philadelphia chromosome of CML.
The fusion protein is 210 kDa and a constitutively active tyrosine kinase. Inhibited by Imatinib



C-Abl: Phosphorylated involving ATM in response to cis-platinum



CaBP1 - 8: Genes for CaBP1 - 8



CaBP: Ca2+-binding protein; alternate splicing produces CaBP1 & CaBP2; bind with high affinity to IP3R at N-terminal 600 aa



CACODYLIC ACID: Dimethylarsonic acid = Dimethylarsinic acid. One toxic organic metabolite of Arsenic poisoning. Tissues have widely differing
rates of methylation of Arsenite - skin is low



CAD: (a) Caspase activated DNAse. (See Apoptosis.) It has a single gene in mammals. CAD is not indispensable for cell death. Without CAD, death
is slower, with DNA degradation, activation of PARP, depletion of NAD & ATP & cell death

(b) CRAC activation domain; conserved residues in the cytosolic tail of STIM1, allowing activation of Orai1

(c) Coronary artery disease



CADHERIN: Cell adhesion molecule, with the extracellular extensions have 5 repetitive sub-domains and form homophilic bonds with those from adjacent cells; bonding is Ca2+-dependent, of on/off type. The cytoplasmic domain is highly conserved, binding p120-catenin, α- & β-catenins and actin - the linking to the latter by α-catenin to EPLIN +/- formin & vinculin

CADHERIN-11: It can be used as a blood tumour progression maker for prostate and pancreatic cancer



CADMIUM: Atomic weight (12C) = 112.4, Ionic radius = 0.97 Å; Damages mitochondria, with cytochrome c release and Caspase-9 activation; causes
Ca2+ release from the ER and inhibition of SERCA pumps; the ER stress/disruption activates Caspase 12



cADPr: Cyclic ADP ribose; believed to be the physiological agonist for type 2 RyR



CAF: Cancer-associated fibroblast



CAFFEINE: An agonist of RyR, causing a sharp and smooth (but brief) rise in cytosolic Ca2+ (but can also inhibit KATP channels, allowing Ca2+ entry
via the plasma membrane through voltage-gated Ca2+ channels)



CALBINDIN: A mature neuronal marker



CALBINDIN 3: (CALB3, CaBP9k, ICaBP, Calbindin D9k.) An S100 family member, but arising from human chromosome Xp22. It is unusual, in
being monomeric



CALCEIN: Used for fluorometric determination of Calcium concentration

CALCEIN AM: A cell membrane-permeable derivative of Calcein



CALCILYTICS: Allosteric inhibitors of the CaSR



CALCIMIMETIC: Organic compounds that can stimulate the CaSR



CALCIMYCIN A23187: Calcium ionophore III



CALCINEURIN: A phosphoprotein serine phosphatase; sensitive to Calcium levels - activates NF-AT transcription by dephosphorylation of NF-AT; a process opposed by GSK3β. Calcineurin causes exposure of the nuclear localization signal for NF-AT, resulting in it translocating to the nucleus, reversed by GSK3β. Sensitive to Cyclosporin A and involved in positive selection in the thymus; involved in Ca2+-dependent apoptosis routes (eg dephosphorylation and activation of Bad), enhancing Bad's heterodimerization with Bcl-x, promoting apoptosis



CALCINEURIN B: The regulatory subunit of protein phosphatase 2B (CLNB)



CALCIOSOME: An unique organelle containing IP3R



CALCITRIOL: 1,25-(OH)2-D3. This active form of Vitamin D is (normally) largely formed in the kidney by 1α-hydroxylase from 25-OH-D3, which has been formed in the liver. In plasma, 85 % is bound to Vitamin D-binding protein, and 15 % bound to albumin; the active free form is less than 1 %. It has a circulating half life of 3-6 h, with clearance relatively constant; binding is to receptors chiefly in bone and the gut, but also elsewhere. Macrophages and monocytes also have 1α-hydroxylase and may be capable of generating 1,25-(OH)2-D3 in certain states, such as lymphomas, especially if stimulated by interferon-γ



CALCIUM: Divalent metal, Atomic weight (12C) = 40.08, Ionic radius = 1.66 Å, Van der Waal's diameter = 0.462 nm, whose ions play key roles in cellular and membrane functions, being an important second messenger. In general, spike rises are seen with receptor pathways, with lower, longer rises, with NFAT. Binds to Centrin, Calmodulin, ER (STIM1 & 2), Sfi1p and microtubules (in particular), with ER/SR binding involving calreticulin and calsequestrin. The level of free Calcium in the cytoplasm is ~70-100 nM, and diffusion is x~100 times slower than most other atoms/molecules, due to many binding sites, allowing for sub-cellular domains. The estimated levels within the ER lumen show wide variations: by EM, the total Ca2+ may be ~5-50 mM, by SR/cytosol distribution ~700 mM (sic; taken from a review [1999], but original article [1997] has μM !, x 1/1000 difference) and by InsP3 mobilization ~5-10 mM. Values given using fluorescence or bioluminescence for Ca2+ are ~2-3 mM, 1-5 mM, 200-1,500 μM (for SR; cell-type dependent, rat ventricular myocyte, ~85-120 μM), MIN6 β-cells, ~250 μM; the free level given as ~300-800 μM. The extracellular level ~1-2 mM. The total level in the Golgi may be ~>10 mmol/L. Appears to stimulate/trigger movement of cilia. May be displaced by Lithium. Calcium in the nucleus regulates cell proliferation, whereas, in the mitochondria, it arrests microtubular-based mitochondrial movement and regulates apoptosis (by lessening it, until toxic). Depletion of Ca2+ in the ER results in inhibition of protein synthesis, some stress-related proteins are stimulated, and apoptosis is induced

[Ca2+]o = Calcium ion concentration outside the cell/plasma membrane

[Ca2+]i = Calcium ion concentration inside the cell/plasma membrane

[Ca2+]sr = Calcium ion concentration within the sarco/endoplasmic reticulum

Intracellular Calcium overload (toxicity) is considered to cause necrosis, from multiple types of cell injury and the activation of the Calcium-activated hydrolysing enzymes. However, increased concentrations of cytosolic Ca2+ may occur at the start and end of apoptosis; both ER Ca2+ and capacitative Ca2+ influx can be apoptogenic



CALCIUM CHANNELS: See SOC. Various types:

Cav; voltage-gated, eg L-type (LTCC)

Those gated by physical factors (temperature, stresses etc.), often members of the TRP family

Those gated by Ligand-Receptor activation (some are TRP)

Store-operated Calcium channels (SOC), activated by store depletion ; linked to phospholipase C and inositol 145-trisphosphate. Subtype CRAC are found in immune cells and are very Calcium-selective, and remain open as long as antigen signal operate and stores remain depleted. Stores are relatively small (ER ~1-3% of cytoplasm volume, SR ~1.5-7.5% of cytosol volume). Capacitative, responding to decreased stores

L & T. T-type can show oscillatory activities in the Zygote/embryo, possibly linked to the underlying process behind the K+-channel oscillations



CALCIUM GREEN-1: A florescent dye used to measure intracellular Ca2+; a membrane-permeable ester is obtainable



CALCIUM IONOPHOPRE: (Calcimycin A23187) Very selective for Ca2+



CALCYCLIN: (CACY, 2A9, PRA, CaBP, 5B10.) See S100A6



CALDENDRIN: See CaBP



CALGRANULIN A: (CAGA, CFAg, MRP8, p8, MAC387, 60B8Ag, L1Ag, CP-10, MIF, NIF.) See S100A8

CALGRANULIN B: (CAGB.) See S100A9

CALGRANULIN C: See S100A12



CAL1L: Calpactin light chain. See S100A10



CALLA: See CD10



CALM: Clathrin assembly lymphoid myeloid leukaemia; endocytic adaptor, having an ANTH domain that is recognized by the SNARE motif of
synaptobrevin 2



Calm1-3: Isoforms of Calmodulin



CALMODULIN: A widespread intracellular calcium-binding protein. Blocked by Chlorpromazine. Binds/interacts with small conductance calcium-activated potassium channels and guanylyl cyclase-activating protein-1



CALNEXIN: An ER membrane marker & folding lectin chaperone; transmembrane



CALNUC: A marker for the cis-Golgi



CALOXIN 1b3: A peptide epitope within PMCA1; presented as an inhibitor of PMCA1



CALPACTIN: Annexin A2 (Annexin II)



CALPACTIN LIGHT CHAIN: See S100A10; 'CAL1L'



CALPAIN: Neutral cysteine proteases in a large family of isoforms activated by autocleavage triggered by calcium; may be involved in myelin degradation in MS and apoptosis; they can cleave members of the Bcl-2 family (eg Bcl-XL, Bid) also Caspase-12 and XIAP; may target Hsp70 (a protector of lysosomes). Some increase in Duchenne muscular dystrophy and have been implicated in limb-girdle muscular dystrophy



CALPASTATIN: An endogenous calpain inhibitor



CALPHOSTIN C: From Cladosporium cladosporioides; inhibits all isoforms of PKC



CALPONIN: A homology domain in Spectrin ELF1



CALRETICULIN: cC1qR; multifunctional protein involved in scavenger function and low affinity Ca2+ storage in the ER & lectin chaperone



CALRETININ: A marker of immature neuronal cells; a calcium-binding protein that has been used in immunohistochemistry in the diagnosis of mesothelioma and some other conditions; since apocrine tumours of the skin do not demonstrate it but metastatic breast cancers may, it may assist in differentiation; positive nerve fibrils in the lamina propria, muscularis mucosae and superficial submucosa correlate with the presence of ganglion cell in the colon of patients with suspected Hirschsprung's disease



CALSENILIN: A Calcium-binding protein that promotes γ-Secretase cleavage of Notch



CALSEQUESTRIN: Hydrophilic, acidic protein 62 kDa associated with sarcoplasmic reticulum, mainly in the lumen, where it seems to be the Ca2+ sensor. Associates with GAPDH located outside the reticulum lumen and appears to bind to and blocks the alkaline NAD+ binding site. Calsequestrin:calreticulin perinuclear 1:1, peripheral 5:1. It is the major Ca2+-binding protein in the lumen of the SR/ER, and forms a complex with Triadin & Junctin for full control and interaction with the RyRs. It changes its configuration when binding to low/rising Ca2+, and frees up the RyR/Triadin/Junctin complex, allowing the release of Ca2+ from the SR/ER



CALTRACTIN: See Centrin (Caltractin 1 = Centrin 2; Caltractin 2 = Centrin 1)



CALU-3: A neoplastic, airways cell line; can still form good tight junctions



CALVIN CYCLE: (Melvin Calvin, American chemist, b1911). Chemical processes of plant carbon dioxide assimilation.



CALYCULIN A: Inhibits protein phosphatases 1 & 2A



CAM: (a) Chorio(n)allantoic membrane

(b) Cell adhesion molecule

(c) Calcium/calmodulin, 16.7 kDa protein – a major Ca2+ sensor; upon Ca2+ binding, the molecule changes form and binds to targets, chiefly kinases, some specific (eg GSK) and others general, the CaMK family; important at neural synapses with phosphorylated Thr253 rising for ~6 h after status epilepticus, whereas phosphorylated Thr286 rising and persisting for ~24 h



CAM5.2: Marker for epithelial cells



CAMELEON: A fusion protein containing two modified green fluorescent proteins, calmodulin and the calmodulin-binding peptide M13. When Ca2+ binds to calmodulin, the latter wraps around the M13 peptide, increasing fluorescence energy transfer between the two GFPs.



CaMK I: Calcium/calmodulin-dependent kinase I, 38-42 kDa (CaMKIγ 53 kDa); CaMK1α is most common in mammals; a regulator of G1; has a conserved T in the activation loop that can be phosphorylated by CaMKKα or CaMKKβ to form a 'CaMK cascade' and maximum CaMK1 activity; some may translocate; implicated in nerve terminals & neuronal growth, cystic fibrosis, aldosterone synthase and cell cycle

CaMK II: Calcium/calmodulin-dependent kinase II, by 4 genes, α, β, γ & δ, with > 30 isoforms, 50-60 kDa and able to auto-phosphorylate and, accordingly, can act as a 'memory switch'; ubiquitous, but mainly in neurons (~2% of total protein in some regions of the brain) concentrated at synapses, also involved in fertilization, vascular tone, cell cycle (all stages) & cellular differentiation; regulated by multi-site phosphorylation (CaMK IIα T286, T305/6) & targeting to specific effector sites, which may be influenced by phosphorylation; T305/6 phosphorylation prevents the binding of Ca2+/CaM to CaMKII, and an in vivo effective site at T253, which is important for targeting (but with limited distribution, probably because of targeting); the full length form stimulates cell proliferation, whilst a truncated form or T253 inhibits; a component in the Wnt/Calcium/Calcineurin pathway; regulator of G1 (in cytoplasm & nucleus), S, G2/M (at spindle poles)→A→(between poles), with siRNA inducing multiple poles; has a C-terminal association domain that allows it to assemble into oligomers; considered to be important for synapse-mediated (mental) memory storage, forming a complex with NMDAR which can be dissociated by CN peptides – a switch function; increases in cytosolic Ca2+ induces a BECN1/ATG7-dependent Bcl-2-sensitive autophagy by activating CAMK2B & AMPK, which inhibit mTOR

CaMK IIα-hKO: For heterozygous knockout mice – with mutation of the gene (largely relevant in neurons) it is associated with murine models of schizophrenia &/or bipolar disorder, with deficient long term potentiation (memory); test mice exhibit unchanged NSC numbers, increased neurogenesis but a failure in development & maturation

CaMK IIA: Abundant in the brain; associated with learning & memory

CaMK IIB: Abundant in the brain; associated with learning & memory

CaMK IID: Induces apoptosis of cardiac myocytes, regulation of vascular smooth muscle polarization & migration, downregulation of breast cancer cells and apoptosis of core acinar mammary cells to create lumina, a link with G-actin being required (Ca2+ not required) with bundling when Ca2+ is applied

CaMK IIN: An inhibitor protein for CaMK II; the human form is found in dendritic cells; only acts upon active CaMK II

CaMKIV: 65-67 kDa; needs phosphorylation of the T in the activation loop to become active; mainly in the brain, but also immune cells, testis & ovary; translocates nucleus ↔ cytoplasm; may regulate CREB, neurite growth, immune & inflammatory responses & cell cycle

CaMKK: Monomeric, 54-68 kDa; mainly in brain, but also thymus, spleen 7 testis; phosphorylate CaMK1 & CaMKIV, also AMPK



CaMKK1: Gene for CaMKKα

CaMKK2: Gene for CaMKKβ



CAML: Cyclophilin-binding protein; may facilitate Calcium entry into cells



cAMP: Cyclic AMP. Downstream messenger from membrane receptors. Suppresses LAK activity. Mitogenic in many cell types



CAMPTOTHECIN: Binds irreversibly with DNA-topoisomerase I complex and inhibits the re-association of DNA after cleavage by topoisomerase I, trapping the enzyme in a covalent linkage with DNA



CANCER STEM CELL: Described markers include :

AML: CD34+, CD38-

GBM: CD133+, U87+

Breast: CD44+, CD24low/-, Lineage-

Prostate: CD44+, Integrin α2β1hi, CD133+

Retinoblastoma: ABCG2+

Lung Cancer: SP-C+, CCA+

Colorectal Cancer: CD33+, CD133+, CD166+, SW1222, LS180, CCK81 & ALDH1



CaN: (a) Calcineurin

(b) Calcium-activated, non-selective



CANCER STEM CELL: “A cell within a tumour that possesses the capacity to self-renew and to cause the heterogeneous lineages of cancer cells that comprise the tumour.” (Workshop on Cancer Stem Cells -AACR)



CAND: An inhibitor in the Cullin/E1-3/NEDD8 system



CANNIZZARO REACTION: Reaction of an aldehyde in a strong base:

2Alkyl-CH=O + NaOH  ⇒  CH2-OH + Alkyl-COO-Na+

producing a mixture of an alcohol and a salt of a carboxylic acid.



CAP: (a) Cbl-associated protein

(b) College of American Pathologists



CAP37: See HBP



CAPACITATION (of Spermatozoa): The change produced in spermatozoa by incubation (several hours; ~1 h for mouse, ~2 h for human) with female-derived fluids (and others), which makes them able to fertilize. Albumin can do for some; some require stimulants +/or nutrients in vitro. Removal of Zinc may be important. Capacitation seems unique to mammals, and can be associated with hyperactivity (hyperactivity does not necessarily imply capacitation).



CAPACITATIVE CALCIUM ENTRY: (=SOCE) The cellular response to the sensed prolonged drawings from Calcium stores, subject to overshoot; a coupled activation of special Calcium channels in the plasma membrane, generally most active at the cell periphery (possibly the volume beneath the membrane effect). Full NFAT activation requires capacitative calcium entry. It is not generally found in cells subject to excitation. (So called, because of similarities to the behaviour of an electrical capacitor) There has been a suggestion that the channels are held in vesicles, to be opened to the plasma membrane as required. The actin cytoskeleton may also be important for channel action. See store-operated Calcium entry



CAPE: Caffeic acid phenyl ester; blocks NF-κB nuclear trafficking



CAPS: (a) Catastrophic anti-phospholipid syndrome

(b) Cryopyrin-associated periodic syndrome, associated with polymorphism of the NLR family member NLRP3: eg familial cold auto-inflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS) and neonatal-onset multi-system inflammatory disease (NOMID)



CAPSAICIN: An activator of TRPV1



CAPSAZEPINE: A blocker of TRPV1; a capsaicin antagonist; can reduce osteosarcoma-induced hyperalgesia; blocks calcium channels; inhibits hypo-oestrogenic bone loss and suppress NOS in macrophages



CAPSID: the protein coat surrounding the DNA or RNA of a virus



CAPZ: Actin-capping proteins



CAR: Cancer associated retinopathy; can be associated with antibodies to α-Enolase, particularly the epitope 56-63 (RYMGKGVS)



Car: Calcium sensing receptor



CARBACHOL: An acetyl choline analogue; in pancreatic islands, activates the m3 muscarinic receptors & releases Ca2+



CARBONYL: R-CO-R'



CARBOXYL: R-COOH



CARD: Caspase activation and recruitment domain; see Inflammasome



CARIPORIDE: A NHE1 inhibitor



CARMA1: An adapter protein which acts with HPK1, resulting in increased IKKβ activity in T cells



CARMUSTINE: An alkylating drug previously used for malignant brain tumours. Largely replaced by Temozolomine



CARNASOL: A phenolic antioxidant phytochemical (found in Rosemary); may block the Hsp90 protection of AhR, with resultant fall in AhR and, potentially, a decline in transcription of CYP1A1 & CYP1B1



CARNITINE: A natural metabolite that transports /transfers long-chain fatty acids into mitochondria; carnitine & TRAIL are said to have a synergistic anti-cancer effect, reversing resistance and enhanced the expression of Bax;



CARRAGEENAN-λ: An inhibitor of HPSE; linear sulphated polysaccharides extracted from (red) seaweed; named after Irish derivation. There are three types - kappa, iota and lambda



CARTWHEEL: A formation of spoke-like structures at the proximal end of the centriole. Located near in the cylinder are gamma-tubulin, NIMA-related kinase Nek2-interacting coiled coil protein C-Nap1



CAS: An adapter molecule phosphorylated by FAK/Src complex



CASA: Computer-assisted sperm analysis



CASK: A PDZ domain scaffold protein, 120 kDa, calcium/calmodulin-dependent serine protein kinase that binds to syndecans; the human homologue of the C. elegans LIN-2. It is a member of the membrane-associated guanylate kinase protein family, with an SH3 domain, a PDZ domain, guanylate kinase domain and a calmodulin-dependent kinase domain. It binds to P2X3 in neurons, and preferentially to syndecans-2 & -4, and it is probably largely a scaffold



CASP3: Gene for Caspase-3. If non-functional, the resultant cell may have a resistance to Caspase-induced apoptosis

CASP8 652 6N del polymorphism: A 6 nucleotide deletion mutation of Caspase 8 gene; may confer a reduced cancer risk for some ethnic groups



CASPASE(S): A family of Cysteine-aspartate proteases involved in the common pathways of apoptosis. They can affect (by cleavage) some 100->200 targets

Caspase-1 Monocytes, dendritic cells, epithelial cells & keratinocytes; involved in pyroptosis; may perform a platform function in ASC-mediated necrosis

Caspase-2 Intranuclear and intra-Golgi. May cleave Golgin-160

Caspase-3 Activated by Apoptosome/Caspase-9; the mutual/shared effector for caspases-8/-10 (TNF/TRAIL/Fas ligand pathway) and caspase-9 (stress/DNA damage-induced cytochrome-C release); proteolytic fragments p32→ p17 + p10

Caspase-4

Caspase-5

Caspase-6

Caspase-7 Activated by Apoptosome/Caspase-9; an executioner, similar to Caspase-3; can localize to the ER and interact with grp78

Caspase-8 TNFR1 endocytosis is necessary for it to be activated by a soluble adaptor complex, to dimerize with FLIP or itself being sufficient for activation

(ie no enzymatic processing) for anti-apoptosis roles, but cleavage is required for apoptosis roles, by a process that may take 3 h after the endocytosis of the TNF/TNFR1, with nuclear β-catenin required to convey resistance to TNF-induced apoptosis; procaspase-8 (p53/55) binds to FADD by its DED and is activated, with p43/41 and p20 products. Forms DISC, activating FADD and caspase-8, leading to apoptosis. Caspase-8 & FADD suppress RIPK-3-mediated necroptosis. Can activate Bid. Inhibited by CrmA; Cullin-3 polyubiquitination promotes activation; Caspase-8 can replace Caspase-1 in cleaving pro-IL-1β; can cleave and inactivate RIPK1; with H2O2, Caspase-3 may be activated by Caspase-8, rather then Caspase-9; a high level of cleaved Caspase-8 in GBM confers a better prognosis

Caspase-9; Procaspase-9 x7 bind to the Apoptosome complex of Apaf-1 and Cytochrome-c. The total complex activates Caspase 3 &/or caspase 7; it is active as a processed dimer (a heterotetramer); TNF (MEF) can initiate a cascade that bypasses Apaf1 and has Caspase 8 activating Caspase 9 (requiring Asp349), from which a 38 kDa fragment then causes lysosomal membrane permeabilization; caspase 9 can have a dual role, as an activator of effector caspases (requiring the apoptosome, Apaf-1 to activate Caspase-3), and as a lysosomal membrane permeabilization inducer (with or without Caspase-8 activation); murine Caspase-9 has the key target point for Caspase-8 action (Asp349) which is not conserved in human Caspase-9 – a Caspase other than Caspase-8 may be involved instead

Caspase-10

Caspase-11 Can process pro-IL-1β in mice

Caspase-12 Located in the ER; reported to be activated when the ER is stressed and Ca2+ increases; cleaves Caspase-9

Caspase enzymes activated during apoptosis cleave over 100 substrates.



cAspAT: Cytoplasmic Aspartate aminotransferase; one of four shuttles for mitochondria



CASPR: NCP-group protein (see neurexin); contactin is required for the cell surface expression of CASPR



CASPR2: Found in juxtaparanodes (nerves) and associates with K+ channels



CASSETTE: (Dictionary: Container of film, magnetic tape, etc. for insertion into equipment.) As used in Biology :

(a) ATP-binding cassette (eg ABCG2), where the cassette is the molecular pocket around the ATP molecule

(b) Others



CAST: (a) CAZ-associated structural protein

(b) Calpastatin; an endogenous calpain I



Casr: Gene for CaSR



CaSR: Ca2+-sensing receptor; belongs to family C of the G protein-coupled receptors, with 612 aa extracellular, ~250 aa transmembrane helices and a C-terminal tail of ~200 aa; long arm of Chromosome 3 (3q13.3-q21), mainly occurring in the parathryoid glands, but also in the thyroid and kidney (also lesser sites). It is targeted to the ER, dimerizing by disulphide bonds and glycosylated. When stimulated, it activates Gq/11, Gi and G12/13, with the stimulation of PLC, which can produce IP3 in addition to other factors. It is not easily desensitized; being associated with filamin A and actin, making it less able to be endocytosed. A number of ions can activate it : Mg2+, Sr2+, La3+ and Gd3+ and some highly charged organic molecules (= type 1 agonists). Type 2 agonists require some Ca2+ present. These usually bind to the TMD, but some amino acids can bind to the ECD. It tonically inhibits PTH secretion & parathyroid cellular proliferation (as well as other effects)



CAT: (a) Chloramphenicol acetytransferase

(b) Cathepsin



CaT1: See TRPV6



CATALASE: Enzyme that reduces H2O2. In the test tube, bubbles of oxygen are released. Most catalase is found in peroxisomes (minor in mitochondria); over-expressing intracellular catalase may protect cells from the cytopathic effects of ascorbate (implying that, without the catalase, H2O2 was the major toxic component); mammalian spermatozoa generally lack appreciable catalase.



CATASTROPHE: Breakdown; depolymerization of microtubules



CathB: Cathepsin B



CATHELICIDIN(S): Mammalian proteins containing a C-terminal cationic antimicrobial domain . One (PR-39, porcine) induced neutrophil migration, with natural heparan sulphate and chondroitin sulphate as co-factors



CATHEPSIN: A family of proteases typically found in the lysozyme and secretory granules and, to a lesser extent, endosomes. Normally they digest components for destruction or re-cycling but, if spilt into the cytosol, they can activate members of the caspase family

CATHEPSIN B: Chromosome 8p22. Reported to be the most abundant cathepsin in the lysosomes; alternative splicing can modify activity. Secreted as an inactive proenzyme 43 or 46 kDa (depending upon glycosylation); trafficked via late endosomes and activated in lysosomes, single chain, 31 kDa. It undergoes pH shape changes; in mildly acid conditions it can be an endopeptidase, whereas, in the acid lysosome, it is an exopeptidase. In vivo, it may act like Cathepsin L. It is normally in perinuclear vesicles, but in transformed cells, becomes scattered and membrane-associated. Present in interstitial fluid of solid tumours and acts like trypsin. Activated by lactate. Cleaves after a pair of basic aa. It degrades collagen, proteoglycans, fibronectin, laminin. It is secreted by malignant tumours and is a bad prognostic sign; it appears as a high molecular weight active form, stable at neutral pH; may be involved in pro-IL-1β cleavage in microglia with a number of conditions (how lysosomal to cytoplasm movement occurs is unclear) and Streptococcus/pneumococcus pneumoniae can do likewise; enhances release of mitochondrial cytochrome c and subsequent caspase activation; can cleave Bid to tBid under neutral pH in vitro promptly (within 4 h); release from lysosomes by Granulysin and cell death can be detected by 2 h, but continues past 6 h, cell PI+ being largely complete by 30 min

CATHEPSIN D: Gene for Cathepsin D; a non-hormone-responsive element-containing target gene

CATHEPSIN D: Endosomal/lysosomal aspartic protease enzyme, 32 kDa. There can be partial release from lysosomes on permeabilization of the plasma membrane with digitonin; leaving the ~pH 3.5 to ~neutral pH range, which does not appear to affect activity appreciably. Its release from cells may precede cytochrome c release and loss of membrane potential in apoptosis; triggers Bax activation (independent of Bid) with selective AIF release during the early stage of apoptosis in T-lymphocytes; after an apoptosis trigger, maximum cytoplasmic activity may be reached at ~10 min; mice deficient in Cathepsin D die at about d 25, with intestinal mucosal atrophy and massive destruction of B- & T -lymphocytes

CATHEPSIN G: Lymphocyte-associated enzyme that degrades SDF-1 at its NH2 terminus in the bone marrow

CATHEPSIN L: A lysosomal cysteine protease; cortical thymus epithelial cells express high levels. Degrades collagen, elastin, fibronectin, laminin

CATHEPSIN S: Microglia, alveolar macrophages, mature monocyte-derived macrophages; medullary thymus epithelial cells express high levels; survival neutral pH; can process neurocan and phosphacan (brain chondroitin proteoglycans). Degrades collagen, elastin, fibronectin, laminin and chondroitin proteoglycans



Cav: Voltage-gated Ca2+ (channel); Cav1 & Cav2; have pore-forming α1 subunit, which associates with a β subunit. Families :

Channel type

Deactivated by sustained

CaV1: L-type

-60 ─ -10 mV

CaV2: N-, P/Q- & R- types

-120 ─ -20 mV

CaV3: T-type

-100 ─ -60 mV



CAV-1 or CAV1: See Caveolin-1



CAVE: Term for a cell surface-connected structure, off which are caveolar invaginations



CAVEOLAE: Plasmalemmal vesicles or flask-shaped invaginations about 65 nm in diameter with an opening ~45 nm across, often arranged around a vacuolar domain, consisting of 100-200 molecules of caveolin per unit. Found in most cells, with the exception of neurons & lymphocytes. They may be formed in the Golgi and carried (as carriers of caveolin) to the plasma membrane. Formed by lipid domains with caveolin-1 and cholesterol in or on exit from the Golgi, forming DRMs and regarded as specialized lipid rafts. Cholesterol is more conspicuous around the neck, with caveolin:cholesterol 1:1; cholesterol seems to bind to tryptophan, also serine. The cytoplasmic side may have fine projections, possibly oligomers of caveolin. Upon internalization, they join with caveosomes or early endosomes to unload their cargo, but remain discrete. Their intracellular destinations can be regulated. Simian virus 40 and Cholera toxin are well-studied ligands for Caveolae binding to Ganglioside GM1; abundant on adipocytes, endothelial cells and muscle: highly conserved



CAVEOLIN-1: The main antigenic component of caveolae, but non-essential for raft endocytosis. It is a dimeric protein of alternatively spliced α and β isoforms, that binds cholesterol (one CRAC motif typical, another VTKYWFYR), with half-life >10 h. It can form 350 kDa complexes with 14-16 monomers. It is involved in the internalizing of sphingolipid toxins; considered by some to be a tumour suppressor by inhibiting signalling molecules and migration; may inhibit and stabilize budding. Others disagree !



CAVEOLIN-2: Often co-expressed with Caveolin-1; generally redundant, but may regulate the location of caveolin-1



CAVEOLIN-3: Mainly in skeletal and cardiac muscle; can take over the role of Caveolin-1. Muscle expression may be influenced by amphiphysin 2/Bin1 (M-Amph2)



CAVEOSOME: A vesicle formed by internal detachment of a caveolar invagination from the plasma membrane; distinct from the early endosome



CAVICLE: See Caveosome



CAVIN1: A component of the Caveolar complex and is required to maintain caveolar invagination. It does not bind to Cav1 at the Golgi



CAZ: Cytomatrix at the active zone of the presynaptic plasma membrane (or presynaptic grid).



CB: (a) Cord blood; its stem cells and progenitors may behave differently from those from adults - the CB stem cells may maintain their immaturity better

(b) Cryobiopsy



CBA: Cytometric bead array; a kit test for TNF-α (at least)



CBC: (a) Cone bipolar cell

(b) Complete blood count; a somewhat meaningless term (like FBE), but usually includes haematological measurements (rather than biochemical measurements) such as the : Haemoglobin, haematocrit, mean (red) cell volume, mean cell haemoglobin, total white cell count, the differential counts (neutrophil, lymphocyte, monocyte, eosinophil, basophil and any early forms) and platelets, with some extra derived parameters



CBD: (a) Cholesterol binding domain

(b) Cannabidiol



CBF: (a) Cilial beat frequency. A relatively small (16%) increase may result in a large increase (56%) in surface liquid velocity

(b) Core binding factor; a transcription factor associated with Notch in vertebrates eg CBFα2 - See Runx1



CBI: Chinese botanicals & isolates



Cbl(-SETA): Adaptor protein, a kinase inhibitor and E3 Ubiquitin ligase, found on Golgi and associated with Src



CBP: Creb-binding protein (p300); phosphorylated CREB Ser133 competes with NF-κB p65 Ser276 for CBP binding, which is in limited supply; an increase of CBP decreases NF-κB-induced responses



Cbp: Raft-associated adaptor



CBT: Cognitive behaviour therapy



CC10: See CCA



CCA: Clara cell specific marker



CCAAT: See C/EBPα



CCCP: Carbonyl cyanide m-chlorophenylhydrazone; an uncoupler of oxidative phosphorylation



CCD: (a) Cytochalasin D

(b) Charge coupled device (eg a camera)

(c) Coiled-coil domain

(d) Cortical collecting duct (of renal tubules)



CCE: Capacitative Ca2+ entry; SOC



CCK: Cholecystokinin (see under latter)



CCK-8: A proprietary cell counting kit based upon the use of ah highly soluble tetrazolium salt. The cells reduce this by dehydrogenase activity to a yellow formazan dye, which is liberated into the culture medium and can be quantified colorimetrically. The linearity of the cell count then depends upon the constancy of the dehydrogenase activity per cell (possibly an assumption)



CCL: Monocyte chemo-attractants.

Ligands Series :

CCL1 TCA-3

CCL2 Transpresentation of IL-15 on IL-15Rα allows expansion of IKDC for TRAIL-dependent killing, responding to TLR3 & 4, for CCL2, critical for movement of IKDC into tumour beds

CCL3 MIP1α

CCL4 MIP1β

CCL5 RANTES

CCL7 MCP-3

CCL8 MCP-2; expressed by osteoblasts stimulated by NFATc1

CCL11 eotaxin

CCL12 MCP-5

CCL19 ELC

CCL20 MIP-3α

CCL21 SLC

CCL22 A ligand for CCR4; produced by human ovarian cancers and their associated macrophages; Treg-associated

CCL24 eotaxin2

CCL25 TECK



CCM: Curcumin



CCN1, 2 & 3: Genes for CCN1, 2 & 3; null or deficiency of CCN1 or 2 in mice is lethal, with deformities, vascular & skeletal respectively; generally very sensitive to environmental factors; TGF-β strongly influences via SRE, with TGF-β requiring 3 CCN2 promoter elements, a SMAD binding site, an ETS tandem repeat and a transcription element (eg MMP3); most are activated, but CCN3 is suppressed. Oestrogen is a potent inducer of CCN1, UV light induces CCN1; they are generally induced by IL-1, TNF-α, bacterial & viral infections; hypoxia & mechanical force induce CCN1 & 2. The human CCN1 maps to 1p21-31, corresponding to the region for AVSD1. In humans, loss of CCN6 results in progressive pseudo-rheumatoid dysplasia (mice seem unaffected). Forced expression of CCN1 in breast cancer cells promotes resistance to apoptosis by up-regulation of XIAP and resistance to Taxol via an integrin αvβ3 mechanism . The gene promoter for CCN1 has 2 TCF4 binding elements; β-catenin/TCF4 specifically bound



CCN: Family of 6 secreted cysteine-rich, matricellular proteins that regulate diverse cellular activities by binding to integrin receptors; found at sites of angiogenesis, such as inflammation and wound healing, where they support cell adhesion, spreading and induce adhesive signals, including activation of FAK, paxillin and Rac; have 4 conserved cysteine-rich domains with ~cysteine residues, having a non-conserved hinge, that is vulnerable to proteolysis. Binding to some integrins may be independent of binding to others. Some promote cancer growth, others inhibit. Some have been implicated in (unwanted) fibrosis production

CCN1/CYR61 angiogenic inducer; binds to integrins αvβ5 & α6β1, affecting migration and regulated by β-catenin; binds with HSPG Syndecan-4 as co-receptor, generating ROS, activating JNK; is up-regulated, stimulating cell proliferation and survival after hyperoxic lung damage in the mouse. Not expressed in healthy human livers; elevated in HCC/adjacent liver, higher in cirrhotic liver around cancer in cytoplasm; β-catenin/p300 elevates mRNA/protein, especially at sites of injury. Binding to integrin induces sustained ERK1/2 activation. This pathway bypasses the anti-apoptosis NF-κB route. CCN1 can generate ROS, amplified with TNFα ~ 4 h; chemotactic; can displace bFGF from the ECM; can modulate Wnt signalling (variable); forms complex with LRP1; can be regulated by Wnt and promote HCC; found higher in more differentiated HCC and after hypoxia & trauma; may be able to limit fibrosis by inducing cellular senescence, having a number of roles

CCN2/CTGF angiogenic inducer, released by α granules of platelets in early tissue repair; can generate ROS; binds to LRP1 & 6, the latter modulates Wnt signalling; binding to integrin induces sustained ERK1/2 activation; chemotactic; potentiates TGF-β and modifies response, binding by a vWC domain; binds BMP-4 & blocks the latter's binding to receptors; CCN2-VEGF blocks binding to VEGFR2 (MMPs may release VEGF); may potentiate fibrosis (eg with TGF-β). It is overexpressed by pancreatic cancer and is indicative of bony metastasis by breast cancer; can be regulated by Wnt

CCN3/Nov angiogenic inducer; supports migration; chemotactic; may be important in CD34+ haematological stem cell renewal; binds & inhibits BMP-2; may affect Notch signalling

CCN4/Elm1/Wisp-1 Promotes cell survival, migration & proliferation; over-expression inhibits cell migration; can be regulated by Wnt, being regulated by β-catenin/p300, also stimulated by LPS; induces cell proliferation and EMT in murine lung

CCN5/COP1 Overexpression inhibits cell migration; inhibits cell proliferation

CCN6 May suppress Wnt signalling in the embryo and inflammatory breast cancer



CCNA2: Gene for cyclin A2



CCNE2: Gene for cyclin E2



CCP: Clathrin-coated pits



CCP1: Cytosolic carboxypeptidase-1; involved in the processing of Glutamate residues from β as well as α tubulin; creating δ2 tubulin from α tubulin by removing the last 2 carboxy-terminal residues



cC1qR: Calreticulin



CCR: Receptors for ligands of the CCL series

Receptors:

CCR1

CCR4 Receptor for CCL22 & CCL17; expressed by human ovarian cancer-associated Tregs

CCR5

CCR6 Chemokine receptor 6; Expressed by stimulated APC's

CCR7 Receptor for T-zone chemokines CCL19 & CCL21

T cells CCR7+ are called central memory cells; also express lymph node homing receptors and little effector function



CC-RCC: Clear cell renal cell carcinoma



CCSP: See CCA



CCV: Clathrin-coated vesicles



CD: (a) Crohn's Disease

(b) Cytoplasmic domain

(c) Coherance domain

(d) Cluster differentiation of lymphocytes & other (some key ones listed). Often performed by passing the specifically stained cells (with others) through a small counting aperture (Flow Cytometry). Counts, with the plotted scatter by size &/or intensity can be divided into clusters :

CD - main forms

CD1a-e: Cortical Thymocytes; dendritic. α-galactosylceramide binds to CD1d, the resulting complex binds with great avidity to the TCR. CD1d is found on APCs, thymocytes, haematopoietic stem cells, B cells and epithelial cells; mapped to Chromosome 1q. Cattle lack CD1d

CD2: Thymocytes, T cells, most NK cells, B cells

CD3: T cell receptor

CD3γ-ε: T cells

CD3ζ: T cells, NK, macrophages

CD4: T helper/inducer cells: see Th1, Th2 & Th17

CD5: Mature T cells, thymocytes, B cell subset; presenilin knockout blocks CD5 expression in thymocytes

CD6: Mature T cells, B cells subset, medullary thymocytes

CD7: Very early lymphoid marker, mature T cells, NK cells, immature myeloid subset

CD8αα: A subset found in the thymus. They can cross-present antigenic peptides. There are ~30% of DC in the medulla in the neonatal mouse, but ~80% in the adult.

CD8α,β: Cytotoxic/suppressor T cells, NK subset, thymocytes. Lack causes reactivation of L major infections. Produce IFNκ. CD8dim = CD8αα

CD9: Platelet, activated T cells, other; cell differentiation antigen

CD10: A neutral endopeptidase. Pre-B cell subset, cortical thymocyte subset, granulocytes/monocytes

CD11a-d: Leucocytes: CD11a = LFA-1: CD11b in mouse auto-fluoresce, a marker for NK cell maturation. CD11c: Dendritic cells, cross-presenting lymphoid (CD+) DCs (~1%)

CD11b/CD18; Integrin αMβ2; Macrophage antigen-1; Mac-1; myeloid & progenitors



CD13: Myeloid-associated marker; aminopeptidase N; involved with the attachment of TNF to blood vessels

CD14: Macrophage (mammalian), monocyte, 55 kDa; LPS receptor (when combined with LPS-binding protein); involved in apoptosis/engulfment (probably with other factors); has membrane (mCD14) and soluble (sCD14, in serum) forms. sCD14 may 'switch-off' activated T cells; interacts with ICAM-3 for leukocyte apoptosis; lectin-like; signalling by HMGB1 through TLR4in macrophages requires CD14 in lipid rafts

CD15: (SSEA-1) A common γ chain cytokine. It may be a weak inducer of Foxp3 in CD4+ CD25hi. Has been used as a marker to enrich GSC instead of CD133

CD16a: IgG Fc receptor; NK, macrophages, mast cells and monocytes; the acquisition by NK cells of CD16 marks a reduction in proliferation capacity. Most NK cells in viscera are CD16-.

CD16b: Granulocytes & neutrophils

CD18: See CD11b; also LFA-1/ICAM-1; leukocyte marker; integrin

CD19: Precursor B cells, B cells, follicular dendritic cells. Not expressed by leukaemic stem cells; a component of the CD21 complement receptor complex, that amplifies signalling by the BCR when co-ligated by an opsonized antigen

CD20: Gene belongs to the MS4A gene family

CD20: (B1 antigen) Precursor B cell subset, B cells. Found on lymphoma stem cells and ~95% malignant B cells. Myeloma stem cells may express, but more differentiated cells (of that series) do not. 33 kDa, with higher values  by increased phosphorylation, dimerization, tetramerization and ~200 kDa complex; found on the plasma membrane, loosely bound constitutively by aa 219-225 to lipid rafts on microvilli, close to the BCR, in association with sIgM and, when mAb is ligated, dissociates from the BCR & IgM, uses some of the Ca2+ channel activation pathway of the latter (a function lost in the absence of the BCR), the channel activity related to an association with cholesterol. Raft bonding increases with anti-CD20 mAb attachment, which triggers homotypic adhesion, actin rearrangement, mitochondial and lysosomal movement to the contact membrane. There is a report that it has been identified on ~1-2% of malignant melanoma cells, probably stem-like cells, thereby extending cell-associated specificity. Treatment of patients having malignant melanoma with Rituximab was claimed to reduce the 'melanoma sustaining cells' and induce tumour regression.

CD21: Complement receptor; mature B cells, follicular dendritic cells, thymocyte subset. See also CD19

CD22: B cell marker; enhances Ca2+ extrusion by co-localizing the tyrosine phosphatase Shp1with PMCA4, the PMCA pumps tending to be co-localized with the CRAC channels

CD23: low affinity IgE receptor. Found on follicular dendritic cells in the apical light zone of tonsillar follicles; activated CD19 cells

CD24: Lymphoid progenitor marker, particularly for B cells (eg CD10+ CD24+); the cells do not circulate in peripheral blood; a key ligand is HMGB1

CD25: Regulatory; α chain of IL-2 receptor. Activated T & B cells, stimulated monocytes, macrophages. CD4+ CD25+ inhibits Th1 cell responses. CD25bright or CD25hi (or similar, meaning very strong antibody decoration, usually in association with CD4+): Regulatory T cells (Treg), about 2-12% (median 5.8%) of adult human peripheral CD4+ and ~ 5-10% or 13% of murine CD4+

CD26: Dipeptidyl peptidase IV activity, 110 kDa on the surface of human T cells; soluble (sCD26) is in blood, enhances transcription of IL-6 & TNF in monocytes and cytosolic ERK1/2, & nuclear NF-κB p50/65, c-FOS & CUX-1 ; degrades SDF-1 in serum

CD27: On naive or memory CD8+

CD28: A co-stimulatory receptor with the TCR in the central synapse; activates movement of components to the synapse, influences transcription and prevents NFAT leaving the nucleus. CD4+ T cells deficient in CD28 are associated with increased inflammatory and atherosclerotic parameters. This subset may be expanded, and has some killer immunoglobulin receptor-like features, show cytolytic ability, releasing perforin, and produce IFNγ. Loss of CD28 may indicate senescence. Ligands B7.1 & B7.2. An homologue of CTLA-1; functionally linked to TNFR2

CD29: α4b1 integrin

CD30: Member of TNFR family, and found on Reed-Sternberg cells; dependent upon activation & proliferation of both T & B cells and in DP medullary thymocytes, also B cells areas near germinal centres; monocytes & macrophages are negative. CD30L (26-40 kDa) is found on thymic medullary epithelial cells & Hassall's corpuscles. It has a precursor (84 kDa) both may be found on/around the Golgi & on the plasma membrane

CD31: Marker for endothelial cells; PECAM-1; indicator of potential oxygenation

CD32: Fc receptor γII

CD33: Myeloid progenitors. Not on leukaemic stem cells

CD34: Haematological precursor & endothelial cells. See CD133. CD+lin- seem to mark pre-leukaemic stem cells (myeloid)

CD35: Neutrophils, eosinophils, monocytes, follicular dendritic cells, B cells, erythrocytes, T cell subset

CD36: Single transmembrane-helix glycoprotein associated with long chain fatty acid transport; thrombospondin receptor; MW 88 kDa; highly glycosylated, with two transmembrane domains. It is expressed by monocytes, macrophages microvascular endothelium platelets & some erythroid cells. It is involved in apoptosis recognition by macrophages; receptor for oxidized LDL and binds to a diverse array of ligands (not fucoidan). Involved in the taste receptors for fatty acids; regarded as a scavenger receptor



CD38: Haematopoietic and plasma cells. A multifunctional ecto-enzyme; uses NAD+ as a substrate to generate ADPR, cADPR & NAADP; (Stem cells, including ALL stem cells are typically negative.)

CD39: An ecto-ATPase

CD40: Member of the TNFR superfamily; produced by activated CD4 cells and APCs such as dendritic cells. The link with its ligand CD40L is necessary for CD25+hi generation; failure results in low CD25+, production of IL-10 and autoimmune conditions. Induces IL-12 secretion; stimulates B cells and dendritic cells to produce cytokines, FasL, TRAIL & TNF; it and its ligand are necessary for the B cell germinal centre centroblasts stimulated transition to centrocytes; dimer is ligand (=CD154). Antibodies can activate it. RIPK1 is required for CD40 ligand-induced apoptosis



CD43: Leukosialin; found on NK cells & marker for development

CD44: Hyaladherin; Phagocytic glycoprotein-1 (Pgp-1), human gpHermes, ECMR III, H-CAM; 19 exons with many isoforms; fatty acylated, transmembrane raft protein; main receptor for Hyaluronan; thymic homing receptor; found on stem cells (considered by some as a marker) & high level on DCs; a T-cell differentiation antigen; involved in maintaining mouse breast development after birth and preventing apoptosis - links with HS; also binds ankyrin at the (gp85)CD44's 306GGNGTVEDRKPS320 motif, without which, lymphocytes cannot respond to HA-dependent cellular adhesion. CD44 anchors MMP-9 to the growing edge of oesophageal cancer and may assist invasion; the GAG component is not essential for MT1-MMP-CD44 complex formation; can be located in invadopodia of breast cancer cell line (MDA-MB-231) and stimulate NHE1 activity causing invasion (RhoA→ROCK1)

CD44v6: may have a special role in cancer - controversial

CD44v10: A major HA receptor in aortic endothelial cells

CD45: Large molecule; all haematopoietic cells; needed for TCR signal transduction in mature T cells, and constituting ~40% of total protein-tyrosine phosphatase activity; ~90% activity is produced by H2O2, with inactivation of phosphorylation of proteins & c-Jun N-terminal kinase. No known ligand; has phosphatase action necessary for Lck (p56lck) activity, countering the Csk kinase and other actions; may promote Src kinase activity at edge of synapse (because of size). In DT40 cells, it may account for ~40% of tyrosine phosphatase activity, which is destroyed by H2O2; may mediate H2O2- activated PLCγ2 to hydrolyze its substrate.; in addition to its negative /phosphatase activity, it may have a positive role in oxidative stress signalling. Seems involved in positive selection, but not negative selection in the thymus.

CD45R: B220

CD45RA: A high molecular weight isoform of protein tyrosine phosphatase CD45. Marker for naive/resting T cells; medullary thymocytes

CD45RBlo: 'Memory' cells, can be regulatory; CD45RBhi: 'naïve' cells, can be active effector cells

CD45RC

CD45RO: Memory activated cell marker; cortical thymocytes

CD46: Involved in regulating the complement cascade and perforin



CD48: Ligand for CD2; associates with LFA-3/CD2/CD48; involved in initial CD4-target cell interactions

CD49: α4b7 integrin

CD49f: CD49F+ HSC tend to be ERDJ4+



CD52: Clusters lipid rafts



CD54: ICAM-1; intercellular adhesion molecule 1; integrin



CD56: NK, T cell subset; only found in high order primates; 140 kDa isoform of NCAM, a member of the Ig superfamily. CD56bright are the primary source of NK cell-derived cytokines (eg IFN-γ), and may be associated with auto-immune conditions, whereas CD56dim have a cytotoxic function (eg granzymes, perforin); both can kill activated CD4+ T cells. CD56 can bind to FRFR1 and, by this, mature from bright ⇒ dim. Degranulation of murine activated CD4+ T cells was enhanced by IL-2, IL-15, (IL-12+IL-18) & IFN-α, with IL-7 & IL-21 stimulating NKbright degranulation of CD4+ T cells

CD57: Germinal centres, T helpers for B-cell Ig production



CD59: Protectin; a raft-associated protein; inhibits the formation of complement membrane attack complexes



CD62E: E-Selectin; associated with endothelial cells

CD62L: L-Selectin; associated with regulatory T cells; lymph node homing receptor; lost with activation, but only after 5 - 6 divisions

CD62P: P-Selectin; associated with platelets



CD68: Macrophages & microglia; macrophages produce IL-7; 'tingible body' macrophages (do not express F4/80; usually express MFG-E8). A scavenger receptor; human homologue of rodent macrosialin. Myeloid marker

CD69: Marker for lymphocyte activation, also positive and negative selection in the thymus



CD71: Transferrin receptor



CD79a & b: Igα & β

CD80: B7-1; CD4 activity marker induced on Treg

CD81: Of the tetraspanin family; putative receptor for HCV, Plasmodium falciparum and P. yoelii (murine) with the E2 glycoprotein binding to the large extracellular loop. Its presence alone is insufficient for viral entry. It is one of a trimolecular complex of CD81-CD19-CD21 to enhance the response by the BCR signalosome, particularly for complement-coated pathogens



CD83: Surface & cytosolic marker for mature dendritic cells, but a cytosolic marker only for immature dendritic cells



CD86: B7-2; CD4 activity marker induced on Treg. Marker for DC maturity; co-stimulatory molecule; a marker for trogocytosis



CD90: Thy-1

CD91: α2 Macroglobulin receptor; LRP. It binds calreticulin at the phagocytic cell surface and may bind to gp96, a heat-shock/stress protein released when cells die by necrosis



CD94: Invariant component of the C-lectin-type receptors broadly expressed on NK cells; forms an inhibitory heterodimer with NKG2A on NK cells

CD95: Fas; a 'Death' receptor, recruited to lipid rafts, with downstream targets such as mitochondria; histochemical stains include G247-4, NOK-1, NOK-2, 4H9 and MIKE-1; the first was considered best;



CD98: Transmembrane glycoprotein, required association for amino acid transport

CD99: 32 kDa cell surface molecule widely expressed; highly expressed on Ewing's sarcoma cells



CD103: Integrin subtype, αEb7; a Treg marker, probably following Foxp3 expression; possibly involved in Treg induction



CD105: Endoglin; a selective decorator target of neo-vascular endothelial cells. It is a receptor for the TGF-β1 molecule, which is up-regulated in tumour angiogenesis

CD106: VCAM-1

CD107a: Lysosomal marker = LAMP-1; its presence on the cell membrane indicates recent damaged cell membrane response

CD107b: Lysosomal-associated membrane protein = LAMP-2



CD115: CSF-1 receptor



CD117: Stem cell factor receptor; Haematopoietic progenitor, tissue mast cells, c-Kit



CD120a: (p55) TNFR1/TNFRSF1A or α; most TNF biological activities are probably through this receptor; the cytoplasmic part has a death domain; activation

leads to the NF-κB path (lipid rafts) or to Caspase-8 & -3 apoptosis (after endocytosis)

CD120b: (p75) TNFR2/TNFRSF1B or β



CD122: The IL-2R β chain; a factor in IL-15 stimulation



CD127: IL-7Rα; may be down regulated during Treg initiation - inversely with subsequent up-regulation of CD122



CD132: common γ-chain

CD133: Phytoerythrin, also prominin-1. Neural stem cell surface marker, related to CD34. 120 kDa transmembrane x 5; can be cell-cycle dependent



CD137: (4-1BB) Probably involved in Treg activation/activity

CD138: Syndecan-1; Plasma cells



CD147: EMMPRIN/OX-47. Transmembrane glycoprotein. Believed to be a chaperone for MCT1. See Basigin.

CD148: A membrane protein tyrosine phosphatase - inhibitory for T cell activation; an intermediary for cell adhesion to S2ED, with involvement of β1 integrin



CD151: =PETA-3: Platelet-endothelial cell tetraspan antigen-3; a protein of the tetraspanin group; involved with the laminin-binding integrins – α3β1, α6β1, α6β4 & α7β1. Binding between laminin and α3 & α6 is direct, not requiring CD151 for expression; expression of CD151 on cancer cells is associated with a poor prognosis; some are involved in kidney and skin development, and may link the integrins to tetraspanin-enriched microdomains; with basal breast cancer cells, CD151 affects α6 integrin-associated changes (see integrin, talin, TEM & actin)

CD152: Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4); an high affinity counter-receptor for B7-1 & B7-2 that inhibits T cell proliferation, IL-2 production and cell cycle progression

CD153: Member of TNFR family; expressed on activated T cells and macrophages. See CD30L

CD154: CD40 ligand (CD40L)

CD155: Poliovirus receptor

CD157: An ecto-enzyme; BST-1



CD158: An inhibitory marker found on CD8+ T cells



CD161: (NK1.1, NKRP1A); NK & NKT cells



CD164: =MGC-24



CD166: ALCAM; neurolin; DM-GRASP; SC-1; may be a marker for colon cancer stem cells



CD178: (FasL) Fas ligand



CD206: Mannose receptor

CD207: Langerhans cells



CD209a: DC-SIGN; C-type lectin



CD222: Cation-independent Mannose-6-Phosphate Receptor (CIMPR); 300kDa



CD: Cytochalasin-D



CD2AP: CD2-associated protein; a permanent membrane resident; See BCR



CDB3: Cytoplasmic domain of band 3 (region close to the red cell plasma membrane surface).



Cdc2: = Cdk1= p34Cdc2~Cdc28(yeast). Combines with Cyclin B kinase: regulates the onset of M phase. Become dephosphorylated/active at the time of separation of the centrioles. Combines with Cyclin B1 to form a complex which phosphorylates histone H1. A kinase associated with Golgi break-up at Mitosis. Phosphorylates GM130. Cdk1 phosphorylates Eg5, which allows its binding to centrosomes. Phosphorylation at Thr14 & Tyr15 by Cdc25 inactivates. At late prophase Cyclin B/Cdk1 moves into the nucleus and achieves full activity



Cdc14: Inactivates Cyclin B/Cdk and activates anaphase promoting complex which destroys the mitosis-specific cyclins. ~66-67 kDa. Cdc14A seems to be associated with the centrosomes: over-expression gives rise to centrosome splitting and spindle defects; under- expression results in failure to split and cytokinesis. Dephosphorylates the Ser315 of p53, acting as a Cdk/aurora antagonist



Cdc25: (Cell division cycle.) Phosphatase activated by Achk1 &2. Has dual phosphatase action. Dephosphorylation of Cdc2 activates the latter, and blocks the G2/M checkpoint. Three isoforms :

Cdc25A - Localized in nucleus. Present & increases from late G1 through mitosis. Lack causes cycle delays. May be involved in chromatin condensation in the nucleus where it activates Cyclin/Cdk after the Cdc25B initiation

Cdc25B - Localized in nucleus & activates mitosis in the cytosol, ~70 kDa; appears during S phase & goes with mitosis. Activity peaks before Cdc25C's: lack⇒block in G2. Seems to be the controller of Cdc2 activity, but can be replaced by Cdc25A. Activates Cyclin A- and Cyclin B1-containing complexes. Most is intranuclear, appearing in S, but seems to move into the cytoplasm/centrosome in G2 and disappear in prophase, with N-terminal specificity. It induces mitosis. Translocation to cytoplasm is induced by UV. May be a steroid-receptor co-factor. May be displaced from the nucleus by Cdk1/Cyclin B1 and hydrogen peroxide. Activates Cyclin B1&Cdk1 on centrosomes

Cdc25C - present throughout the cycle: blocks G2⇒M, but cannot block the cycle alone. Is inactive through most of the cycle, being activated by Cdk1(Cdc2)/Cyclin B1. Seems less important than the others. When phosphorylated at Ser216, it is bound to 14-3-3 protein and withdrawn from activity

Cdc25A & B are chiefly intranuclear, some Cdc25B in the cytoplasm in G2. Both are involved in cancer metabolism/development. Nuclear export of Cdc25B is needed for activity - possibly to the centrosome



Cdc2C: Cytoplasmic Cdc2, by movement from the nucleus. Mediated by phosphorylation of Ser216 by Chk1 &/or 2 and binding with 14-3-3 structural proteins.



Cdc31: Yeast gene homologue of Cetn



Cdc42: A Rho family GTPase involved in the actin remodelling beneath an immune synapse; redirects GPI-anchored proteins into sorting endosomes; crucial involvement with E-adherin activities and associates with Par complexes for endosomal sorting



Cdc45: An essential replication factor



CDDO: 2-cyano-3,12-dioxooleana-1,9(11)-dien-(28)-oic acid; a triterpenoid. Some cancers are sensitive to some triterpenoids and their derivatives, involving apoptosis, in which GSK-3β seems to be phosphorylated (inactivated)



CDF: Difluorinated curcumin; a curcumin analogue



CDG: Congenital disorder(s) of Glycosylation

CDG-IIc: Leukocyte adhesion deficiency Iic; LAD II; see OMIM 266265

CDG-IIf: See OMIM 603585



CDH: Genes for cadherins & related

CDH1: Gene for E-cadherin; on chromosome 16q22.1

CDH2: Gene for N-cadherin; "mesenchymal" - can interact with FGFR. Tumour cells expressing it can link better with stromal components; with FGF2 there is a synergism for migration, invasion and proteolytic enzyme secretion

CDH3: Gene for P-cadherin

CDH4: Gene for R-cadherin

CDH5: Gene for VE-cadherin

CDH11: Gene for Cadherin-11 = OB-cadherin; "mesenchymal"; normally expressed by osteoblasts and stromal cells; when expressed by cancers, is associated with poor prognosis, promoting homing to bone; induced by Snail, Slug & ZEB2/SIP1. Tumour cells expressing it can link better with stromal components

CDH13: Gene for T-cadherin (Truncated- or heart-; on chromosome 16q24); membrane tethered by a GPI anchor & tends to be apical

CDH24: Gene for Cadherin-24

PCDH24 = PCLKC: Gene for LKC-Protocadherin = cadherin-related protein 24;

PCDHBx: Clustered protocadherin

PCDHGx: Clustered protocadherin

PCDGGx: Clustered protocadherin

PCDH1: Protocadherin-1

PCDH8: Protocadherin-8

PCDH9: Protocadherin-9

PCDH10: Protocadherin-10 = OL-Protocadherin

PCDH11Y: Protocadherin-11Y = PC-Protocadherin

PCDH17: Protocadherin-17

PCDH18: Protocadherin-18

FAT4: Gene for FAT4

RET: Gene for RET

PCDH20: Protocadherin-20



Cdh1: Activator of Ubiquitin ligase APC; found at/in pericentrosomal matrix



CDK: Cyclin-dependant kinase. Cdk-1/Cyclin B. Cdk1=Cdc2. Associates with centrosome at prophase. Cdk-2/Cyclin E or A, activates centriole separation (with others). See Cdc2. Cdk-5, a serine/threonine kinase, is unlike the other Cdks in that it is not involved in cell cycle control, rather, that it is involved in neural development and associates with a p35



cdk4: A gene involved in the up-regulation of the cell cycle; reported up-regulated in a variety of tumours - breast cancer, mantle cell lymphoma and large B-cell lymphoma



CDK5RAP2: A protein associated with γ-tubulin targeting

CDK11/p58: An endogenous mRNA; only translated during mitosis, involving an IRES element



CDMPR: Cation-dependent Mannose-6-Phosphate Receptor



cDNA: Chromosomal DNA (as opposed to mitDNA [mitochondrial])



CDR: Complementary determining region of TCR: three loops that combine with the peptide/MHC are flexible, so that multiple peptides may be recognized.



CDR2: Complementarity-determining region; antigen of cTEC & rare non-epithelial cells of thymic medulla



CD28RE: CD28 response element (gene promoter). Those of IL-2 & GM-CST bind both NFAT & Rel-family



CDS: Circular dichroism spectroscopy



Cds1: See Chk2



CE: (a) Convergent extension; the narrowing and extension of a group of cells

(b) Cell envelope (as of keratinocytes/corneocytes, with insoluble material such as involucrin, loricrin etc.)



CEA: Carcinoembryonic antigen; probably the first cancer marker identified and studied. It is expressed at low levels by normal tissues, but is typically expressed by tumours of the gut, pancreas and lung (non small cell). It is also expressed by the thymic medullary epithelial cells, which may explain its low antigenic activity. Immune assault against CEA-producing tumours is by CD4 T cells and (presumably) NK cells



CEACAM: Gene family that includes the gene for CEA

CEACAMs:

CEACAM-1 A transmembrane cell-cell adhesion protein, down-regulated in breast cancer; has shown a considerable evolutionary drift from mice to humans; phosphorylation of cytoplasmic Thr457 is necessary for acinar lumen formation and is probably performed by CaMKIID, resulting in apoptosis of the central acinar cells; expressed by human thymic medullary epithelial cells

CEACAM-5 Gene for human CEA, missing in the mouse

CEACAM-6 Expressed by human thymic medullary epithelial cells



C/EBP: CCAAT enhancer binding protein alpha; a family of transcription factors with at least 6 isoforms : -α; a key inhibitor of cell proliferation, especially hepatoma and myeloid. Knock outs express high levels of cell cycle proteins. It needs to have Ser193 (rodent) Ser190 (human) phosphorylated to be active as an inhibitor; DNA binding involves other regions. Mechanism for growth retardation in the liver seems to be protein-protein interactions, but DNA binding in leukaemia. Insulin leads to dephosphorylation of C/EBPα via PI3K/Akt pathway. They bind to certain Cdks and inhibit cell division.



CED-1: (Cell death) A scavenger receptor of C. elegans, with similarities to SREC. It is attracted to cell corpses near the cell membrane; has 16 atypical EGF-like repeats.



ced-6 (gene; murine): Encodes a 304 aa protein; 93% homologous with the human CED-6



CED-6: A linker receptor protein, that links downstream with CED-1



CEF: Chicken embryo fibroblasts



CELECOXIB: Selective inhibitor of COX2; anti-inflammatory medication; may have a more direct effect on tumours



CELL ADHESION MOLECULES: neurexins, cadherins, integrins, sidekicks



CELL DEATH: Generally referring to a non-apoptotic death; this can be induced by death receptors, with the type of death process influenced by the influence type, the interaction of key molecules (FADD, RIP, TRAF2, & JNK)the presence of ROS and oxidative stress. The caspases are influenced by oxidative influences, and may be inactivated, directing death signals to necrosis (and, in turn, creating ROS, forming a positive feedback loop)



CELL VOLUME: When calculated from membrane capacitance measurements on ventricular myocytes, there is an assumed volume:capacitance ratio of 6.76 (rat) or 5.39 (ferret) pF/pL



CELLUBREVIN: R-SNARE protein rescues exocytosis when there is deficiency in synaptobrevin 1. Required for proper synapse maturation and brain function, but not for the initial formation of synaptic contacts. See Synaptobrevin



CELLULAR RETINOL BINDING PROTEIN (CRBP)



CELLULAR RETINALDEHYDE BINDING PROTEIN (CRABP):



CEM: Human lymphoblastoid cell line; CEMss do not express caveolin



CEN1: Gene for Centrin-1. The human gene is found on 18A2. Cen1p can be found in the testis and retina - probably cilia-related

CEN2: Gene for Centrin-2. The human gene is found on Xq28

CEN3: Gene for Centrin-3. Cen3p is more like the yeast homologue CDC31; it is found in centrosomes generally in small amounts. It can be found in nasal epithelium



CENEXIN: A protein found at/in the pericentrosomal matrix throughout the cycle, located in association with the mother centriole



CENP-E: Centromere-associated kinesin-like protein; located to the kinetochore corona fibres - capture the microtubule plus ends and stabilize them



CENTRIN: A conserved group of acidic proteins MW about 20 KDa, of the EF-hand superfamily of calcium-binding proteins. Calmodulin shares approx 45% sequence identity with Centrin. May have 10 isoforms. >90% is not associated with centrosomes. Centrosome-associated centrin has a specific pattern and is concentrated in the distal lumen of the centrioles and attached to fibres at the proximal end. Seems to be a connector in lower organisms (Rootletin in higher). Foreign centrin causes delayed cleavage and microtubules and asters are impaired. Humans and mice have 4 centrin genes - Cetn-1 to 3, ?4. There are corresponding proteins :-

HsCen-1: Centrin-1: is produced only by male germ cells and retinal sensory cells

HsCen-2: Centrin-2: is a centriole protein. Recombinant GFP-centrin-2 localizes to centrioles through the cytokinesis cycle. Blocking production prevents duplication of the centriole in HeLa cells, leading to enlarged spindles, multi-nucleation, failure of cytokinesis and cell death. Is found intranuclear, complexed with XPC and HR23B (See Nucleotide excision repair). Considered to be a cancer biomarker that may influence HDAC augmenting the HDAC inhibitors, particularly with CTCL cases; the relationship of intranuclear and centriolar Centrin 2 is unclear. Has 2 C-terminal Ca2+ sensor domains and binds to Sfi1p

HsCen-3: Centrin-3: localizes to pericentriolar material, & is less homologous with Cen1 & Cen2 and a larger molecule.

HsCen-4: Centrin-4: Similar in structure to Cent2, accumulates to centrioles and Procentrioles, with 2 variants which do not. Has different targets to Cent2 & 3 - Found in brain (ependymal & choroidal ciliated cells in basal bodies) kidney, lung and ovary. ? ciliogenesis.

Human Centrins 1 & 2 have phenylalanine 4th from the amino-terminal end, and tyrosine at the carboxy-terminal end. Tryptophan is not included. Both ends have aa not found in calmodulin. Centrin in Xenopus ova/zygotes combines with Hsp70 & 90, the former dissociating in acid conditions, the latter with increase in Calcium. They sequester the centrin and probably place a block on development until the centrin is released.



CENTRIN GENES: Three Cetn-1 to 3. Those for centrin 2 & 3 are expressed during cell division. Proteins are produced early in centriole assembly. Centrin 1 & 2 are involved in ciliary beating. See Cetn-1 to 3



CENTRIN PHOSPHORYLATION: This occurs at Serine residue 170 during G2/M phase of cell cycle. Strong in prophase and metaphase. PKA can phosphorylate centrin in vitro. It possibly heralds centriole duplication.



CENTRIN PLATE: An arc-shaped plate immuno-decorating with anti-centrin antibodies, seen in the blastocyst cells of mammalian embryo. Microtubules seem to emanate from it towards the plasma membrane. It may coincide with the increase in aerobic respiration.



CENTRIOLE: A relatively rigid structure of 9x3 tubules (A,B and C), the triplets arranged around a lumen at an angle to the radius, the number declining to pairs at a smaller angle to the tangent towards the distal end. Towards the distal end there is a ring of satellites from which arise microtubules (during interphase) and appendages. The lumen near that end contains centrin 3 and Vfl1p and has a thickened inner lining which may show calcium stimulated contractility. The proximal end has a 'cartwheel' and contains gamma-tubulin, Nek2 and C-Nap1



CENTRIOLE DUPLICATION: Normally appears to occur close to existing centrioles, but can form slower without an existing template. The procentriole is the earliest indicator for prophase. The older one duplicates first and is anchored. Is stimulated by damage to microtubules, stabilized by taxol. If prevented, existing centrioles separate and form spindles with only one at each pole. Daughter cells have only one each. 2nd and 3rd bipolar, defective mitosis may occur, with broad spindle poles. Subsequent cytokinesis produce multinucleated products and finally die. Duplicates G1/S. In immature Drosophila, with Cdk1 (=Cdc2) checkpoint (G2/M) blocked, centrioles go on to become larger (daughter>mother) and, in some, form grand-daughters, with none of the line disengaging. Length does not seem mother-controlled



CENTRIOLIN: An human protein localized to the maternal centriole and functions in both cytokinesis and cell cycle progression. If silenced, cytokinesis is blocked and there is the formation of long intercellular bridges. Continuing mitoses result in multicellular syncytia. Some apoptose during prolonged mitosis, others arrest at G1/G0. Hs homology with budding and fission yeast proteins. Is needed to progress into S phase.



CENTROBIN: A protein the associates with procentrioles and daughter centrioles



CENTROBLAST: The primitive B cell precursor in the germinal centre dark zone. Under stimulation, they transform to centrocytes move into the light zone.



CENTROCYTE: Primitive B cell in partial transition in the light zone of the germinal centres, where there are FDCs and antigen presentation, permitting affinity maturation and rescue from apoptosis.



CENTROSOME: (Diplosome) comprises two centrioles and pericentriolar material. It is more rigid than other cellular components, indents the nucleus and shows 'oscillations' - periodic movements probably derived from the centriole(s). Movement is more pronounced before and after mitosis. Surrounded by Golgi sacks/vesicles which it may influence. Seem important in S phase and completing cytokinesis. Division before cytokinesis seems to involve cyclin-dependent kinase 2, coupling centriole duplication with DNA replication at G1/S. Aberrations of cyclins D & E common in cancer. A subset of PCM proteins are arranged in a tubular configuration with a closed and open end. CEP110 and ninein are found at both ends of the tube. In daughter centrosomes, they are found at the closed end. Both mother and daughter have these plus CEP250/c-Nap1. CEP110 & ninein appear at the open end about telophase-G1. Both are essential for centrosome architecture as well as function as a MTOC. Duplicate G1/S.



CENTROSOMAL MATRIX: Contains several proteins which anchor kinases and phosphatases - the large A-Kinase Anchoring Protein (AKAP450) is a basic scaffold. Over-exposure to C-terminus anchoring, (not coiled-coil/binding sites) blocks normal AKAP450 - impaired cytokinesis & increased ploidy of HeLa cells, fibroblasts stop in G1. Centrosomal maturation can occur without centrioles. Decoration with rabbit serum 0013 reactivity reveals ~ 20 x ~80 nm loosely distributed granules of molecules with high molecular weight. The TuBCs are arranged in association with the negative ends of the nucleated microtubules.



CENTROSOMIN: A factor involved in the attachment of centrosomes to the spindle



CENTROSPHERE: The spindle of mitosis (or meiosis



4-CEP: 4-Chloro-3-ethylphenol



CEP110: A centrosomal protein

Cep135: A centrosomal protein

Cep250: A centrosomal protein against which antibodies may appear in autoimmune conditions. It is a coiled-coil 250 kDa



c-erb-B-2: A surface receptor tyrosine kinase; elevated in MS



Cetn-1 to 3: Genes of mice and men which encode for Centrin-1 to 3 respectively



CERAMIDE: Involved in apoptosis. Induces PKCγ translocation to the Golgi and activation of PKCγ via phosphorylation of Tyr311 and Tyr332. It activates NADPH oxidase, increasing ROS levels, and causes release of Ca2+ from the ER into the mitochondria (via mPTP) bringing about swelling and the release of cytochrome c (inhibited by Bcl-2). Important for raft/platform formation in the plasma membrane and Fas activation; a stress response agonist. Links the ATM apoptosis suppression influence with the JNK/SAPK cascade; also involved in neurons, as a neurotoxic compound, augmented by ROS in response to TNF but, if as a precursor to S1P, it can be pro-survival



CERBERUS: Bind and inhibit the Wnt/Frizzled binding, and also Nodal and Bone Morphogenic Protein



CERTOLIZUMAB (PEGOL): A mAb against TNF-α to treat RA &/or similar conditions



CERULEIN: A cholecystokinin analogue that can induce acute pancreatitis when administered at a dose level above that for maximum secretory activity



CETUXIMAB ('Erbitux'): An immunoglobulin G1 chimeric mouse-human monoclonal antibody that specifically targets the extracellular domain of EGFR. It is best known for the treatment of colorectal cancer, inducing apoptosis



CF: (a) Cytotoxic factor; a cytokine produced by CD4+ T cells of both mice and humans in response to Dengue virus infection. It kills CD4+ cells and H-2A- macrophages, but induces H-2A+ macrophages to produce CF2, which amplifies the effects of CF. Both CF & CF2 may be key players in the severe forms of Dengue infection

(b) Coronary flow



CFA: Complete Freund's adjuvant; additive to antigenic preparations for immunization made from a suspension of Mycobacteria in a mineral oil. The adjuvant prolongs the antigenic exposure and has an augmenting effect on antibody production.



CFC: Colony forming cell(s)



CFIT: Cardiac fibroblast immortalized with telomerase (cf normal primary cardiac fibroblasts that suffer senescence after more than about 5 passages)



CFLAR: See FLIPL



cFLIP: (FLAME, CASH, CLARP & MIT-1) cellular FLICE-like inhibitory protein, 55 kDa with a cleavage product p43; 11 known cFLIP isoforms, with both long cFLIPL and short cFLIPS well represented in cultured tumour cells; a non-catalytic antagonist of Caspase-8, the latter forming a complex with cFLIPL that inhibits RIPK3; associated with a failure of TNF to induce apoptosis in GBM-derived endothelial cells; transcribed mRNA & translated protein in GBM endothelial cells can be detected within 1 h of triggering by TNF/TNFR1/integrin α6β1 (this may be a cell-type specific response); regulated by ubiquitination & proteosomal degradation; elevated levels are thought to interfere with complexes involving caspase-8, thereby suppressing it



c-fms: Transmembrane glycoprotein receptor tyrosine kinase



CFP: Cyan (blue) fluorescent protein; covalently tagged to a protein of interest, then monitored under ultraviolet light



c-Fms: Osteoclastogenic gene



c-fos: Proto-oncogene.



c-Fos: Protein product of c-fos, MW 62 kDa; associated with c-Jun (additive) for AP-1. Deficiency renders macrophages more responsive to LPS-stimulated IL-12. Stimulates endothelial cells from a wound edge



CFSE: Carboxy-fluorescein diacetate succinimidyl ester; amine reactive, vital dye that can follow cell division



CFTR: Cystic fibrosis transmembrane conductance regulator. A collection (aggresome) of filamentous-like structures; the (usual) point mutation (ΔF508) does not prevent Cl- passage, but triggers ERAD-mediated degradation



CFU: Colony forming unit

CFU-E: Erythrocyte colony forming unit (considered more mature than the BFU-E); (cf E-CFU [endogenous-CFU], resistant to X-irradiation, and unresponsive to lithium application

CFU-GM: Granulocyte/monocyte colony forming unit

CFU-M: Megakaryocyte colony forming unit

CFU-S: (Transplantable) pluripotential stem cell



C3G: An exchange factor involved with T10 and insulin signalling



CG0009: An inhibitor of GSK-3α/β



Cγ-1: = PLCγ-1



CGAT-1 & -2: Chondroitin sulphate N-acetylgalactosaminyltransferase 1 & 2



CGI: CpG islands; domains of CpG in DNA that can be subject to methylation as in epigenetic control and silencing of genes



CGIR: Cell growth inhibition rate



cGK: cGMP-dependent protein kinases (=PKG)



CG-NAP: Centrosome and Golgi localized PKN-associated protein; a giant coiled-coil protein localized to the centrosome by the C-terminal end; some homology with Kendrin, and associates with γ-tubulin. It and Kendrin seem to form part of the γ-TuBC and assist attachment to the centrosome



cGMP: Cyclic guanosine 3'5'- monophosphate. A regulator of photoreceptor ion intake and involved in cilial beat frequency (with Ca2+). It is formed through two pathways:

In response to natriuric peptides

By NO-responsive soluble guanylyl cyclase

There are 2 mammalian genes and three isoforms:

Type I is mainly cardiovascular: endothelial, smooth muscle and platelets

Type II is mainly in intestine, kidney & brain



CG-NAP: See AKAP450



CGP3466: Binds to GAPDH and is anti-apoptotic; binds in the channel of the tetramer and splits the molecule to dimers



CGP37157: Inhibits ER-mitochondrial Ca2+ flux



CH: (a) Cluster headache

(b) Chronic hepatitis



CH1: Calponin homology domain (see Spectrin ELF1); smooth muscle tandem forms bind actin; found near the NH2-terminals of β-spectrins



C3H: Mouse strain



CHANZYME: A molecular structure performing two functions – as an enzyme and as an ion channel (eg TRPM2)



CHAPERONIN: Cytosolic chaperonin-containing t-complex polypeptide 1 (CCT, CTP, TRiC). A double doughnut with 16 subunits; ~900 kDa each doughnut. with 8 different subunit species. Binds, stabilized and folds nascent proteins and denatured peptides using ATP :

Actin

Tubulin α,β,γ

Myosin

Cyclin E

VHL tumour suppressor

Transducin

Luciferase

Mason-Pfizer monkey (retro-) virus-Gag

HBV capsid protein

p21ras

Cyclin B

Cofilin depolymerizing factor

Enolase

EBV EBNA-3



CHAPS: 3-[(3-chloramidopropyl) dimethylammonio]-1-propane sulphonate. A zwitterionic detergent favoured to extract transmembrane proteins in their functional state, probably by preserving the protein-lipid bonds and disrupting the protein-protein interactions



CHARYBDOTOXIN: Peptide from scorpion Leiurus quinquestriatus; potent and selective inhibitor of Ca2+-activated K+ channels in certain cells



CHC: (a) α-cyano-4-hydroxycinnamate. Inhibitor of MCT1 and pyruvate entry into mitochondria (= 4-CIN); anion transport blocker

(b) Clathrin heavy chain



CHECKPOINT: Points in the cell cycle where the cycle can be initiated or inhibited (G1) or inhibited (G2M). Each involves the Cdk/Cyclins. They are important for gaining time to repair damaged DNA and to maintain genetic fidelity. Each checkpoint involves factors :

Cell cycle stage

Factors

Radiosensitivity (single)

G1

ATM, Brca1, p53, Chk2, Mdm2

Nil

S

ATM, Nbs1, Brca1, Chk2

Nil

Early G2

ATM, RT dose independent

Nil

G2M

ATM, RT dose dependent

Nil

CHELERYTHRINE CHLORIDE: A broad spectrum PKC inhibitor



CHEMERIN: An adipokine that affects adipogenesis and the glucose metabolism of adipocytes



CHEMOKINE: A subset of cationic cytokines, 8-15 kDa , showing a heightened ability to attract selectively, subsets of leukocytes to sites of inflammation by chemotaxis. Chemicals (eg CXCL12) produced by tissue components (eg stroma) stimulate or inhibit, or cause differentiation or apoptosis in the cells being supported by the stroma. There are similarities with cytokines (which are more of lymphoid/macrophage origin). Most form dimers which dissociate upon dilution, releasing the active monomer. There are 7 transmembrane domains and G protein-coupled receptors, with considerable promiscuity and redundancy, producing robustness. Most have a receptor domain near the NH2- end. There are subfamilies designated by the first two Cysteine molecules :

CC (two Cysteine molecules in sequence) - Chromosome 17 - tend to influence mononuclear cells. Many make up the MCP sequence sub-cluster

CXC (the two Cysteine molecules are separated) - Chromosome 4 - tend to influence neutrophils. Most are exclusive of mammals (CXCL12 & 14 are found in fish). CXCL16 differs; it attracts NK T cells and T cells to dendritic cells and assists with their adhesion

The main clusters are more recent in an evolutionary sense - the earlier genes have fewer products.



CHEMOKINE RECEPTOR: As in table -

Receptor

Ligand

Chromosome

CXCR1

IL-8

2q35

CXCR2

IL-8, GROα,β,γ, NAP-2, ENA 78, GCP-2

2q35

CXCR3

IP10, Mig


CXCR4

SDF-1

2q21

CXCR5

BCA-1


CCR1

RANTES, MIP 1α, MCP-2, MCP-3

3p21

CCR2a/b

MCP-1, MCP-2, MCP-3, MCP-4

3p21

CCR3

eotaxin, RANTES, MCP-3, MCP-4


CCR4

RANTES, MIP-α, MCP-1


CCR5

RANTES, MIP-α, MIP-1β

3



The CXCR4 is unusual because of its wide distribution. Receptors for IP-10, SDF-1 and Mig all have an arginine before the first Cysteine. Chemokines signal through heterotrimeric GTB-binding proteins



CHEMORESISTANCE: The resistance that (usually) tumour cells display to chemotherapeutic agents. It may be inherent for the tumour cell or the tumour type, but generally develops in cells without chemoresistance after exposure to chemotherapeutic drugs. Resistance can be to multiple agents. Types include :

a) Impaired DNA repair

b) Activation of ABC transporters



CHERP: Calcium homeostasis endoplasmic reticulum protein; co-localizes with, and interacts with RyR1 in the release of Ca2+ from the SR



CHERRY: A protein marker



CHGUT: Chondroitin sulphate glucuronyltransferase



CHI3L1, (YKL-40): Chitinase 3-like 1



CHIMERA: A complex structure made from components drawn from others. See TMS



ChIP: Chromatin immunoprecipitation assay



CHIR99021: An aminopyrimidine & very specific GSK-3β inhibitor; IC50 ~ 4 nM (in TCF/LEF reporter assay IC50 ~ 1.5 nM); provides ATP-competitive inhibition of GSK-3; a 12.5 mg/kg ip dose to mice resulted in a maximum brain concentration of 160 nM in 60 min; this would exceed the level to affect GSK-3β (5.7 nM)



CHK: Checkpoint kinases, comprising Chk 1 & 2 and their families



CHK1: Gene for Chk1. Lack is lethal in the early embryo (as for ATR-/-)



Chk 1 & 2: Structurally unrelated checkpoint proteins, usually activated by phosphorylation. Serine/threonine kinases; share some overlapping substrate specificity. Chk1 responsible for cell cycle arrest in response to DNA damage. It is essential. Chk2 is a modulator. Chk2/hCds1 is phosphorylated in response to ionizing irradiation & HU and, in an ATM-dependent manner, in response to ionizing irradiation. Halt cell division to allow time for DNA repair. Chk2/hCds1 has an FHA domain and a SQ/TQ cluster in its amino terminus it phosphorylates & controls :

Substrate

Site

Checkpoint

p53

S-20

G1/S

Cdc25A

S-123

S

Cdc25C

S-216

G2/M

Activation involves oligomerization involving phosphorylation, which can be auto-phosphorylation. Chk1 is activated by phosphorylation at Serine 317, but restricted to S/G2.



CHLORIN: A molecule having a large, heterocyclic, aromatic ring. With Mg2+ in the ring, it is referred-to as a chlorophyll. It is rather similar to porphyrin (which has iron to make haemoglobin). There are other rather similar molecules; bacteriochlorins and isobacteriochlorins. All have come to prominence as the basic molecules for photosenstizers (see Sensitizer)



CHLORINE (Cl): Atomic weight (based upon 12C) = 35.453, in VIIA of the Periodic classification. A poisonous yellow-green gas at room temperature; was used in World War I, resulting in lung damage. It is used in swimming pools to disinfect. An oxidizing agent



CHLOROQUINE: Blocks endosome/lysosome-mediated factors and autophagy



CHLORPROMAZINE: Anti-psychotic drug. Blocks Calmodulin and the Clathrin pathway



CHMP1: Chromatin-modifying protein 1 (homologue of yeast Did2; Charged multivesicular body protein); a nuclear matrix protein controlling chromatin structure and cell cycle progression. It can recruit a gene silencing protein



CHO: Chinese Hamster Ovary cell line. Near the centrioles are numerous virus-like particles in the PCM. Their number fluctuate ~inversely with the microtubular nucleation; irregular shape, 15-30 μm; few ion channels in plasma membrane



CHOLESTEROL: Steroid lipid. A planar molecule, length about x3 protein helix turns and has a small polar head (-OH) which, in membranes should be located near the membrane interface



CHONDROITIN SULPHATE: 4 main disaccharide sulphation patterns :

Cartilage

Derivation

A. GlcUAβ1 - 3-Ga1NAc(4-O-Sulphate)

Whale

B. Dermatan sulphate


C. GlcUAβ1 - 3-Ga1NAc(6-O-Sulphate)

Shark

D. GlcUA(2-O-Sulphate)β1 - 3-Ga1NAc(6-O-Sulphate)

Shark

E. GlcUAβ1 - 3-Ga1NAc(4,6-O-Sulphate)

Squid

As components of proteoglycans (usually with heparan sulphate) they make up much of the extracellular layer that can participate in stroma-to-cell and cell-to-cell interactions. The cell-associated half life in uterine stromal cells is in the order of 5-6 h. The linker tetrasaccharide is assembled before the protein core leaves the cis-region of the Golgi; the core protein takes ~30 min to move from the rough endoplasmic reticulum to the Golgi apparatus, being sulphated in the trans-Golgi network. Secreted amounts are relatively unchanged with time, with 15 - 20 min to move to the cell surface. Macrophages have a pericellular single pool of heparan sulphate (half life ~6.9 h) and a single pool of chondroitin sulphate (~11.5 h); when cholesterol-laden, two chondroitin sulphate pools appeared, with half lives of 0.8 h & 25.9 h. It is a significant inhibitor of axonal growth and neuroplasticity, involving neuronal elongation & axonal growth. It is indispensable for cell growth and differentiation, with disruption of polypeptide growth factors likely; 70-80% of human lymphoid cells contain chondroitin sulphate as the GAG for Serglycin, stimulation with PHA-L increased the percentage

Binds/interacts/with:

Midkine/CS-E

HGF/CS-B, CS-E

FGF3/CS-E (moderate)

FGF5/CS-D (moderate)

FGF6/CS-E (moderate)

FGF7/CS-B

FGF8/CS-E (moderate)

FGF16 &18/CS-E

FGF22/CS-E (strongly)

The structures of FGFs 3, 6, 8, 16 & 22 are not very similar, making elucidation of the binding requirements difficult

Knockdown of murine PAPSTs (and the presumed decrease of chondroitin sulphate) did not affect ESCs in vitro (deficiencies may be revealed in vivo, where motility may be important)

See also MCSP



CHOP: (a) A chemotherapeutic regime for lymphomas, consisting of cyclophosphamide, doxorubicin, vincristine and prednisolone. Approximately 40% of patients with diffuse, large B-cell lymphoma develop resistance. In vitro, chemical inhibition of Akt overcomes CHOP resistance in DLBCL cells, and 1-3-3ζ appears to do so also

(b) CCAAT/enhancer binding protein homologous protein

(c) =DDIT3; constituent of the PERK pathway



CHOP/Gadd153/ddit3: A C/EBP family member; transcription factor that promotes apoptosis by repressing Bcl-2 & promoting Bim transcription



CHP: (a) Calcineurin homologous protein; one of a number of inhibitors of Calcineurin

(b) Cumene hydroperoxide



CHP1: Chromodomain protein 1



CHRn: Chromosome n



CHROMAFFIN GRANULE: (From bovine adrenal medullary cells); Radius ~120 nm (smaller than lysosomes & mitochondria)



CHROMATIDS: Daughter chromosomes



CHROMATIN: DNA, RNA and histone proteins; cf euchromatin & heterochromatin



CHROMOGRANIN: A marker for neuroendocrine origin



CHROMOMYCIN A3: From Streptomyces griseus. A fluorescent stain for DNA; has anti-fungal, -bacterial and -tumour effects, including macro-molecular synthesis from DNA



CHRT: Chemoradiation



CHRYSIN: A natural flavonoid extracted from propolis 'bee glue'; said to have beneficial effects on cancer, including the downregulation of Mcl-1, blocking resistance to TRAIL



cHSP60: Chlamydial Hsp60; co-localizes with human Hsp60 within macrophages in atherosclerotic lesions and can stimulate inflammatory responses via TLR4/MD2



CHSS1 to 3: Chondroitin sulphate synthase



CHT: Chemotherapy



Ch-TOG: A Golgi-microtubule linker



CHX: Cyclohexamide; a translation inhibitor, used to block protein production; it blocks the up-regulation of pro-IL-1β by LPS, but also increases constitutive and inducible processing of pro-IL-1β (it may have an inhibitory effect upon the negative regulator of pro-IL-1β processing)



Ci: Segment polarity gene. Cubitus interruptus (Drosophila), a transcription factor for Hh/Ptc. See also Hedgehog and Gli (vertebrates). Ci has both repressor and activating functions, repressor by the proteolytic product Ci75 (associated with microtubule sequestration), activation by Ci155



CI: Confidence interval; the statistical term for the 95% range about the mean of a population



CIA: Collagen induced arthritis (mouse)



cIAP-1 & cIAP-2: Cytosolic, soluble peptides that recruits TRAF2 to form a signalling complex favouring the TNFR2 pathway; associates with and stabilizes procaspases; see IAP



CIBRACON BLUE 3G-A (Reactive Blue 2): An inhibitor of Phosphoglycerate kinase. Its effects upon early embryos is similar to that of EDTA



CICD: Caspase independent cell death



CICR: Ca2+-induced Ca2+ release; rising cytosolic Ca2+ levels stimulate the RyR to open & release Ca2+ from the ER



CID: (a) Collision-induced dissociation

(b) Caspase-independent cell death



CIE: Clathrin-independent endocytosis



CIHR: Canadian Institute of Health Research



CILIA: Motile appendages from cells. Have a centriole-like basal body fixed to the plasma membrane by centriolar appendages



CILIOGENESIS: Fibrous granules and non-membranous, electron dense granules 70-100 nm diam. appear in cytoplasm associated. Multiple procentrioles grow out of deuterosomes, from which daughter centrioles separate and move to cell apex as basal bodies. These attach to the plasma membrane by appendages off the distal blades and the axoneme elongates



CILOSTAZOL: A drug used to treat intermittent claudication; fears that it may be associated with increased cardiovascular risks may be unfounded



CIMPR: Cation-independent Mannose-6-Phosphate Receptor; Receptor for HPSE



CIN: (a) Cervical intra-epithelial neoplasia; dysplasia and worse

(b) Chromosomal instability



CIN85: Cbl-interacting protein of 85 kDa; required for SLP65 phosphorylation and movement to the plasma membrane; a permanent membrane resident; See BCR



CINACALCET: A type 2 calcimimetic



CINGULIN: Associated with tight junctions



cis: Same cell



CIS: Carcinoma in situ; (pre-)malignant change in an epithelial layer, the changes being retained within the basement membrane (no spread into surrounding tissues)



cis-GOLGI: The cisternae & stacks of membrane-lined Golgi spaces that are located furthest from the centrosome (cf trans-Golgi, medial-Golgi & trans-Golgi network)



CISH: Y-chromogenic in situ hybridization; detection and highlighting of Y chromosomes by linking them with a probe and appropriate decoration



cis-UCA: Suppresses the JNK signalling pathway associated with UV-B on HCE cells



CITRINE: A modified GFP; a protein marker



Ci-VSP: Ciona intestinalis voltage-sensing phosphatase



c-jun: Proto-oncogene



c-JUN: Protein oncogene product and transcription factor of 39 kDa which, as a homodimer, or heterodimer with c-Fos, binds the AP-1 site to activate transcription. It is inactivated by GSK, which phosphorylates c-Jun at 3 sites adjacent to its DNA-binding domain



CK18:P Cytokeratin 18



CK-Iα: Casein kinase I; associates with APC, Axin and GSK3



CKD: Chronic kidney disease



c-Kit: Kit (=CD117), the receptor for SCF; ~50% of human CD56bright CD16- NK cells express it. Normal human blood contains a 'substantial amount' of c-Kit ligands



CL: Cardiolipin



CL-P1: Collectin, a family of C-type lectins, with -P1 found in the placenta; an endothelial scavenger molecule, similar to SR-AI/II



CL100: produces a dual specificity phosphatase; encodes a MAPK3 phosphatase involved in cell proliferation



CLA: See Ly-5



CLA-I: (CD36 & LIMPII analogous-1.) Human; very similar to Scavenger receptor B1 (SR-B1) of mice; 'Human SR-B1' is often used in HCV studies.



CLADE: (Genetic evolution) Branch



CLAP: A domain of Epsin, binding to the clathrin triskelion



CLARA CELLS: Bronchial columnar cells; non-ciliated



CLASTOGENIC: giving rise to or inducing disruption or breakages, as of chromosomes.



CLATHRIN: Involved in vesicle endocytosis at some synapses and forms coats on vesicles; may occur on ~0.6% of plasma membrane (HeLaM). Involves dynamin. In yeast, clathrin facilitates the initiation of endocytic-site assembly but is not needed for membrane invagination or vesicle formation. F-actin dynamics are required for multiple distinct stages of clathrin-coated vesicle formation, including coated pit formation, constriction, and internalization. It is a trimer of 3 ~190 kDa heavy chains, each with an associated 23-26 kDa light chain, the former the more important. Clathrin always colocalizes with AP-2; on the exposed cell surface the molecules accumulate over ~ 30 - 60 s, then disappear; on the contact surface side they can last 2-15 min. Only receptor molecules that enter via clathrin pits can signal.



CLATHRIN-COATED PIT: A sharp membrane invagination caused by a clathrin coat. The periphery of the coat closes in, forming a cup. The radius of the coat can be 350 - 1000Å. Actin dynamics are not involved for the pits



CLATHRIN-COATED PLAQUE:  Enriched in hexagonal clathrin arrays. Actin dynamics, Arp2/3 complex and cortactin are required for the late stage of the plaque



CLAUDIN(S): A family of 27 transmembrane proteins that form junctional strands associated with tight junctions and help determine permeability and selectivity, ~20 kDa; subdivided into classical & non-classical. Epithelia of various tissues express subsets of these claudins. Their presence does not necessarily prove tight junctions. Changes in phosphorylation correlate with changes in permeability. There is an inverse correlation between the number of strands parallel to the plane of the monolayer and the permeability of the junction. Diffusion can be retarded by narrowing the space between the lateral membranes of adjacent cells. Therefore, the distance between the apical-most and basal-most strand (depth) is inversely proportional to the permeability. The junction is subdivided into compartments, which provides a means to amplify the barrier properties of the individual strands. Compartments are formed by the branching and anastomosing of junctional strands. Strands are often associated with gap junctions that become incorporated into mature tight junctions, as is described for many species.

Claudin 1 is down-regulated by transcription factors snail & slug

Claudin 2 increases the permeability of tight junctions to sodium. Phosphorylated Claudin-4 co-localizes with ZO-1



ClC PROTEINS: Class of voltage dependent Cl- channels with several members mutated in human disease. Said to be nine in mammals, highly conserved. Three classes: 1) Plasma membrane (includes ClC-2), also 2) & 3) mainly intracellular membranes

ClC-2 Cl- channel is ubiquitously expresses and generally closed under resting conditions, slowly opening upon hyperpolarization and acidic pH. Seems to play a key role in the 'nursemaid cells': Sertoli & RPE. Defects cause death of the germinal cells and photoreceptor cells respectively.

ClC-5 Cl- expressed by endosomes and probably contributes to their acidification



CICR: Calcium-induced Calcium release



CIMPR: Cation-independent Mannose-6-Phosphate Receptor; Receptor for HPSE



CITRIC ACID: Lemons have 5 – 6 % citric acid, giving a pH ~2.2; component of the citric acid cycle (Kreb's cycle, Tricarboxylic acid cycle)



CK59: Inhibitor of CaMKII



CKD: Chronic kidney disease



CL: Cytotoxic lymphocyte



CLAMP: C-terminal linking and modulating protein. See PDZK1



CLAUDIN: Family of proteins involved in tight junctions; in general, they set the involvement of occludin.

CLAUDIN-4: Claudin-4 and occludin are tightly bound around the keratin 'pearls' in squamous cell cancer



CLASP1 & 2: Clip-associated protein(s); bind to the (+) plus (distal) end of microtubules and associated with CLIP-17- & CLIP-115. Only one CLASP is necessary; they stabilize the distal end of the microtubule with the middle section binding to EB1 and the microtubule, the -COOH end of CLASP2 binds to the cell cortex and Golgi



CLBC: Claudin-low breast cancer; associated with early metastasis & resistance to chemotherapy, having gene markers for EMT;



CLC: Clathrin light chain



CLEC17A: C-type lectin 17A



CLEVER: Common lymphatic endothelial and vascular endothelial receptor; Involved in attachment of lymphocytes to endothelial cells of high venules. See FEEL



CLICK: Cathepsin L inhibitor Kanunuma series



CLIMP-63: A cytoskeleton-linking endoplasmic reticulum membrane protein; p63; ubi1quitously expressed. An ER integral protein, and a Dicer interacting protein, the high molecular weight, electrostatic complex so produced, is catalytically active in pre-micro-RNA processing and excluded from the outer nuclear membrane; CLIMP-63 stabilizes Dicer; moves with Dicer & is glycosylated, then moves through the ER wall; links microtubules to membrane proteins



CLINIPORATOR: Pertaining to application of electroporation in the clinic



CLIPs: Cytoplasmic linker proteins: bind to microtubules and interact with motors & Rab GTPases to modulate the binding of membranes with microtubules for organelle movement

CLIP-70: Microtubule-binding protein that is essential for binding endocytic vesicles to microtubules in vitro and co-localizes with endocytic vesicles in vivo

CLIP-115: Associates with CLIP-170, EB1 at the distal (+) end of microtubules

CLIP-170-RELATED: Have a cytoskeletal-associated protein-Gly motif that interacts with tubulin; active at the organelle-microtubule interface

CLIP FRAGMENT: Portion of Ii, the CLIP fragment, is cleaved in the MHC II compartments, and occupies the peptide-binding groove of MHC II, to be replaced by antigen-derived peptide in the context of DC activation and maturation, using the accessory molecule HLA-DM & HLA-DO (H2-M or H2-DM in mice).

CLIPR-59: A CLIP-170-related protein involved in the regulation of microtubule dynamics, possibly mitochondrial raft-like microdomains; acts as a scaffold protein interacting with, and controlling phospho-Akt. Palmitoylation of two cysteines provides for raft attachment, but only after a molecular bridge has been formed. It is believed to act as a chaperone, linking tubulin and Ganglioside GD3, being slightly faster than the binding of GD3 to tubulin. It may also be involved in trans Golgi membranes



CLL: Chronic lymphocytic leukaemia; usually B cell type; more common in the elderly



CLNB: See Calcineurin B



CLODRONATE: Intravenous, liposome coated clodronate virtually eliminates Kupffer cells and reduces splenic macrophages, without appreciably affecting the circulating monocytes or other tissue macrophages



CLOSTRIDIUM DIFFICILE TOXIN B: A general inhibitor of Rho family GTPases



CLOTRIMAZOLE: Anti fungal agent; interferes with SOCE



CLP: (a) Common lymphoid progenitor

(b) Caecal ligation & puncture (to produce tissue injury & sepsis, particularly affecting the lungs)



CLR4: Cryptic loci regulator 4, an histone methyltransferase



CLSI: Clinical and Laboratory Standards Institute



CLSM: Confocal laser scanning microscope



CM: Conditioned medium (ie medium into which cells have released products that may act as growth factors etc.)



CMA: (a) Concanamycin A

(b) Chaperone-mediated autophagy; HSP70 selects and carries the complex to lysosomes for recognition by LAMP-2A, moving through the wall guided by HSP70 within; oxidative stress (mild) increases CMA, in part by the oxidation of the substrates



c-Maf: Transcription factor, associates with NFAT to transcribe IL-4



4CmC: 4-Chloro-m-cresol; activates RyR1 & 2



Cmd1: Calmodulin



cMDH: Cytoplasmic malate dehydrogenase; one of four shuttle enzymes for mitochondria



CM-DiI: A lipophilic tracer, fluorescent dye for membranes such as the plasma membrane



CME: Clathrin mediated endocytosis; leads to receptor recycling - non CME (NCE) leads to receptor degradation



CMEP: Cortical motor evoked potential



c-MET: Receptor for HGF. The HGF/c-Met pathway is deranged in many cancers. In embryogenesis, the degree of 2-O-uronic acid sulphation of heparan sulphate may play a role in mammary secondary and ductal side branches



CMH: Ceramide monohexoside



CM-H2DCFDA: 5-(& 6-)Chloromethyl-2',7'-dichlorohydrofluorescein



CMI: Cell-mediated immune/immunity



C57MG: Mouse mammary cancer cell line



CML: Chronic Myeloid Leukaemia. Usually has Philadelphia chromosome



CMP-PA: Cytidine monophosphate phosphatidase. Involved in receptor chemistry



CMP-SIALIC ACID: Synthesized in the nucleus



CMRL-1066: Connaught Medical Research Laboratory; culture medium used for Rhesus embryos



CMTMR: 5-(and-6)-(((4-chloromethyl)benzoyl)amino)tetramethylrhodamine; 'CellTracker' Orange dye; fluorescent under UV



CMV: Cytomegalovirus



c-Myc: Gene for c-Myc; a non-hormone-responsive element-containing target gene; a Wnt/β-Catenin target gene



c-Myc: A proto-oncogene, involved in control of cell proliferation, promoting G1-S transition, also differentiation and apoptosis. Its expression is tightly controlled and down-regulated to allow differentiation, and there need to be survival signals for it to influence. Has multiple promoters P0-P3



Cn: Calcineurin



C-Nap1: A Nek2-interacting coiled-coil protein.  Blocking causes centrosome pairs to split. Possibly under control of Nek2, which may phosphorylate C-Nap1. Seems to tether the centrosomes. Dissociates from spindle poles during mitosis, but re-accumulates at end of cell division.



Cnb1: Calcineurin regulatory subunit



C9neo: A complement antigen



CNG CHANNELS: Cyclic nucleotide-gated channels (eg olfactory, retina). There are three olfactory subunits - CNGA2, CNGA4, and CNGB1b



CNI-1493: (N,N'-bis{3,5-bis[1-[(aminoiminomethyl)hydrazono]ethyl}phenyl] decanediamide tetrahydrochloride. It reversibly inhibits phosphorylation of p38 MAPK. At appropriate dose, it inhibits macrophage LPS-stimulated production of TNF-α, IL-1, IL-6, MIP-1α, MIP-1β and NO. It is not countered by INFγ (as is Dexamethasone). It can reduce the severity of diseases involving macrophage function. Its effects last ~4 h, and it does not suppress T cell functions; to be effective, it must be given at ~ onset of symptoms - timing is critical.



CNP: Copy number pleomorphism - where copy numbers of a gene differ in the genome.



CNPase: 2',3'-Cyclic nucleotide phosphodiesterase



CN PEPTIDE: Derived from CaMKIIN; interfere with the binding of CaMKII to brain structures. See tatCN Peptide



CNQX: 6-cyano-7-nitroquinoxaline-2,3-dione. An antagonist at kainite receptors



CNS: Central nervous system; brain & spinal cord



CNT: Connecting segment (of renal tubules)



CNTF: Ciliary neurotrophic factor; astrocytes have the factor repressed by neuronal contact; injury reverses this rapidly, probably byTht1 activated by STAT3



CoA: Co-enzyme A



COATED PIT: See clathrin



COATED PLAQUE: See clathrin; lasts about 2 min before moving inwards shortly before membrane pinching; AP-2 & epsin remain in same proportion throughout



COCKAYNE'S SYNDROME: Autosomal recessive, dwarfism, retinal atrophy, deafness, also progeria, prognathism, mental retardation & photosensitivity.



COCs: Cumulus-oocyte complexes



COELENTERAZINE: (Comes in various forms) Luminophore of the aequorin complex, oxidized by O2 to illuminate at 465 nm when binding Ca2+



COENZYME q10: Ubiquinone



COFILIN-1 (non-muscle): Actin-severing protein; pH sensors that sever and nucleate actin filaments; (see Actin)

COFILIN-2 (muscle): Actin-severing protein; pH sensors that sever and nucleate actin filaments (see Actin)

COFILIN FAMILY: ADF, Cofilin-1, Cofilin-2; for cell migration, cofilin disassembles actin filaments at one end & creates free ends for nucleation & assembly at the plasma membrane; there is de/phosphorylation at the N-terminal & de-/protonation of a Histidine at the C-terminal; the Phosphatidylinositol binding at the plasma membrane is pH dependent; dissociation from the plasma membrane at increased pHi increases cofilin activity; ADF is very pH sensitive, with increased actin-binding at higher pHi



COHESIN: Loaded onto chromatin early in the cell cycle - Telophase ⇒ G1(depending upon activity). Bind the chromatids together until metaphase



Col7a1: The gene for Collagen VII which, when the gene is mutated, results in the clinical conditions of autosomal dominant or recessive Epidermolysis bullosa



COLCEMID (Trade name): Demecolcine; N-Deacetyl-N-methylcolchicine



COLCHICINE: Drug which blocks tubule assembly and, in flagella, their disassembly, possibly by capping the ends.



COLLAGEN: Various types

Collagen I The major structural form in the ECM; stimulated by ascorbate; epithelial cell adhesion is associated with migration

Collagen II

Collagen III Stimulated by ascorbate

Collagen IV Prominent in basement membranes; epithelial cell interaction is stable adhesion. It has 6 different α chains that can assemble into 3 different heterotrimers, showing tissue-specific patterns and changes with development stage. Collagen IV provides mechanical stability, and many cells bind to it by integrins and non-integrin receptors (CD44 & DDR-1). Proteolytic degradation may expose unusual binding sites.

Collagen VII For fibrils to hold the epidermis to the dermis. Defective in recessive dysmorphic Epidermolysis Bullosa

Collagen XVIII Three variants from two promoters, by different splicing

#1(V1C18) Basement membrane -Promoter 1

#2(V2C18) Alternate splicing -Promoter 2

#3(V3C18) Alternate splicing -Promoter 2



COLLAGENASE A: Type IV Collagenase; Mr 72,000; splits gelatin; produced largely by stromal cells around invading tumours cells. Secreted as an inactive pro-gelatinase, it is activated by a proteinase (MT-MMP) on the cell membrane



COLLAGEN PROLYL HYDROXYLASE: Enzymes involved in the cross-linking of collagen precursors; there are 3 different α domains, but all have PDIs as β subunits; belong to the Fe2+-2-oxoglutarate diogenase family and require ascorbate to maintain full catalytic activity



COLLECTIN(S): (Defence collagens) Multifunctional family of proteins with C-type lectin domains and pattern recognition capacity thought to be involved in innate immunity. Included are Mannose binding lectin (MBL), Surfactant protein A (SP-A) and Surfactant protein D (SP-D) and bovine Conglutinin (C1q) an early component of the Complement pathway. They have globular head domains that attach to apoptotic cells and collagenous tails to which macrophages relate with receptors such as LRP



COLO829: An human malignant melanoma cell line



COMET: (a) The appearance of the (+) distal tip of the microtubule when decorated with anti-EB1-GFP and examined under UV microscopy

(b) STIM1 when on the ER when filled with Ca2+

(c) N-Wasp-dependent actin comet tails on GLUT4-containing endosomes; involve PI(4,5)P2, more active for vesicles from lipid rafts



COMP: Cartilage oligomeric matrix protein



COMPACTION: Stage in embryo development, after the 3rd cleavage division, when the outer, now polarized cells lose clear boundaries, prior to the formation of the morula.



COMPLETE METAPLASIA (of stomach): Intestinal metaplasia, with all small bowel enzymes present



COMPLEX I: (TNFR1-related) A multimeric protein complex leading to the polyubiquitination of RIP1 by cAIP proteins; RIP1 can then act as a docking-site for TAK1, TAB2 & TAB3, which can then activate the NF-κB pathway

COMPLEX II: (TNFR1-related) Has core components FADD, RIP1, caspase-8 and acts as a platform for caspase-8 activation and (under usual conditions) the induction of apoptosis; if caspase-8 is ineffective, a necrosome complex can form



COMPLEXIN: Binding activates synaptic SNARE complexes into a metastable state and that additional Ca(2+) binding to synaptotagmin 1 triggers fast exocytosis by displacing complexin from the metastable SNARE complexes



COMP: Catechol-O-methyltransferase



COMPOUND C: An inhibitor of AMPK



ConA: Concanavalin A



CONCANAMYCIN A: (Folimycin) Specific inhibitor of the V-type ATPase responsible for acidification of endosomes and porforin-mediated cytotoxicity



CONCANAVALIN A: Obtained from Canavalia ensiformis (Jack Bean); binds to sugar groups on the plasma membrane and agglutinates RBCs. It stimulates mitosis. Injected into mice, it produces a hepatocellular hepatitis, likened to auto-immune hepatitis. The response depends upon NKT cells releasing and responding to TRAIL (+/- FasL/Fas ?), which induces hepatocyte and NKT apoptosis (6 – 10 h) which can be prevented by Nec-1 & PJ-34. It stimulation the production of, but prevents the localization of MT1-MPP into invadopodia, making the enzyme ineffective



CONDENSIN (I & II): Regulates chromatin condensation and maintains compaction during anaphase; subunits include Smc2 & Smc4, with the two interacting to form an ATPase

CONDENSIN I: Contains, in addition to Smc2 & 4, CAP-D2, CAP-G & CAP-H

CONDENSIN II: Contains in addition to Smc2 & 4, CAP-D3, CAP-D2 & CAP-H2



CONDUIT SYSTEM: A system of small channels that distribute chemokines &/or small molecules of blood origin in the white pulp of the spleen



CONRADI-HÜNERMANN-HAPPLE: Syndrome; X-linked dominant form of chondrodysplasia punctata; mutations in EBP gene



CONSERVED: Similar over a wide spectrum of taxa



CONVERGENT EXTENSION: Cells move between each-other to extend the narrower core structure.



COOMASSIE BLUE (Trade name for Brilliant Blue G: Bradford Reagent): A dye used for protein staining



COP-1: A growth-arrest gene



COP I & II: Coat protein complexes that attach to membranes. These coat proteins can deform membranes



COPPER: (Cu2+): (12C) MW 63.54, Ionic radius (Cu2+) 0.70 Å



CORACLE: Homologue of Protein 4.1 in D. melanogaster



CORD7: Cone-rod dystrophy. Associated with mutations of RIM1.



CORI ESTER: α-D-Glucose-1-phosphate



CORNEOCYTE: Keratinocyte that has differentiated to produce keratin and adopts progressive flattening with a layer of lipid separating the cells



corneodesmosin: Gene for an adhesive protein produced by keratinocytes and involved in terminal differentiation of keratinocytes



CORTACTIN: An actin-binding protein that may be phosphorylated at tyrosine, a process inhibited by microfilaments; found in invadopodia, where cofilin binds with cortactin & sequesters inactive cofilin at the distal membrane of the invadopodia where it can be released with a pHi rise



CORTEX (of cell): A rather ill-defined term no doubt referring to the inner layer of the plasma membrane bilayer, and a narrow band of cytosol beneath the bilayer, perhaps ~ 1-2 μm



CORTEXILLIN: Bundles actin filaments



Cos-2: Costal-2



COS-7: Embryo African green monkey kidney epithelial cells; derivative of CV-1



COSMID: A cloning vector, being a variant of a hybrid plasmid; contains a Lambda phage cos sequence; see also Fosmid



COSTAL-2: Kinesin-related protein



COSTAMERE: Specialized domain at the junction of the plasma membrane and Z-discs in peripheral myofibrils; force buffers protecting the plasma
membrane during muscle contraction



COT: See Tpl2



COX-1 & -2: Cyclooxygenase-1 (70 kDa) & -2 (72 kDa); prostaglandin endoperoxide synthase 1 & 2; catalyse the rate-limiting step in the pathway arachidonic acid to prostaglandin H2, the common precursor to the prostaglandins, prostacyclins and thromboxanes. NFAT stimulates genes. COX-1 is expressed constitutively by most tissues, COX-2 is generally induced (Chromosome 1), with a mean involvement in ~40% if cancers; Colon cancers express NFATc1 & c2, and stimulate COX-2 production, whereas breast cancer express it in 2-100%, with higher values in poorly differentiated tumours, PGE2 inhibits apoptosis by increasing Bcl-2, decreasing Bax & NO signals, but increases VEGF, endothelin-1 & PDGF with CD44 increasing cell growth and arachidonic acid increasing mutagenesis; COX2 is associated with a decreased disease-free interval



CP-690550: see Tofacitinib



CPA: Cyclopiazonic acid, with 5 rings; from Penicillium cyclopium; inhibitor of ER & sarcolemmal reticulum Ca2+-ATPase



CPAE: Calf pulmonary artery endothelium



CPAN: Caspase-activated nuclease (See CAD.) = DFF40



CPAP: Centrosomal component of humans of 1338 aa. Homologue of SAS-4 in C. elegans. Interacts with γ-tubulin complexes



CPE: (a) Cytoplasmic polyadenylation element - See Cytoplasmic polyadenylation

(b) Cytopathic effect

(c) Clostridium perfringens enterotoxin



CPE-R: Clostridium perfringens enterotoxin receptor = Claudin-4



CPEB: CPE-binding protein - See CPE



CpG: Cytosine-phosphate-guanosine; Dinucleotide sites susceptible to methylation of the Cytosine residue - see Imprint; motifs that are immunogenic when clustered and hypo-methylated; common in bacteria and in mammalian promoter regions, said to be found in 60-90% of vertebrate CpG DNA. It causes maturation of B220+ dendritic cells. Its uptake is by non-specific protein receptors, that can be blocked, reaching the endosomes, which must mature (acidify), before later involving c-Jun, which is phosphorylated within minutes. The responses are similar to, but not identical, to those for LPS; both using the SAPK pathway downstream. Substituting Gs for Ts (eg GACGTT to GACGGG) creates inhibitors of the CpG effects, blocking AP-1 transcription in B cells, not affecting the LPS pathway



CPM: Cellular Potts model - for clathrin vesicle formation



cPML PROTEIN: Cytoplasmic promyelocytic leukaemia protein; promotes SMAD's binding to SARA and recruitment to early endosomes



CPP: Cell-penetrating peptide; eg Granulysin, Perforin & Granzyme B; there may be 2 main pathways – endocytosis at low concentrations, and direct penetration at higher concentrations; they are rapidly degraded, with probably two compartments in the cell, one where the peptides are likely to remain relatively intact, and another where there is rapid degradation; there is no (or minimal) cytoplasmic leakage



CPSF: Cleavage and polyadenylation specific factor - See Cytoplasmic polyadenylation. It comprises a group of polypeptides that binds to the AAUAAA and brings poly(A) polymerase to the 3'-terminal transcript. This stimulates translation at the 5' end, possibly by 5' cap ribose methylation. Other factors are needed



CPX: Ciprofloxacin; an quinolone antibiotic; see under NFX



CPZ: Chlorpromazine; inhibitor of Clathrin-mediated endocytosis. It is believed to associate with an adaptor complex (AP-2) and hold Clathrin away from
the plasma membrane



CQ: Chloroquine



C1q: Has a similar structure to MBL; is a hetero-trimer that, by C-terminal cysteines, can form oligomers of trimers; binds calreticulin firmly (as do FasL, TRAIL & MBL), with calreticulin undergoing a structural change over time



CR: Complete regression (eg of a tumour); eventual death from another, unrelated form of pathology



CR2: complement receptor 2; see CD21

CR3: Complement receptor-3; CD11b/CD18; see Mac-1

CR4: Complement receptor-4; CD11c/CD18



CRABP: Cellular retinaldehyde binding protein



CRABTREE EFFECT: A phenomenon noted for many malignant tumours (but not exclusively) that, when glucose is administered, there is an initial speeding-up of aerobic respiration (~50 sec), followed by a degree of inhibition; attributed to a consumption/deficiency of Pi and excess ADP, largely suppressing mitochondrial function



CRAC: (a) Calcium release-activated Calcium channel of immune cells; voltage independent activation, inwardly rectifying, Ca2+ selective

CRACM1 Gene TMEM142A; See Orai1

CRACM2 TMEM142B

CRACM3 TMEM142C

(b) Motif: Cholesterol recognition and/or interaction amino acid consensus; relates to caveolin-1 and its cholesterol binding, but more generally

L/V-(X)(1-5)-Y-(X)(1-5)-R/K-



CRAMBIN: Small 46 aa protein from seeds of Crambe abyssinica - a 'model protein' for protein structure studies



CRASH: Corpus callosum agenesis, mental retardation, adducted thumbs, spastic paraplegia & hydrocephalus; mutation of the L1 gene, X chromosome 



CRBP: Cellular retinol binding protein



CRC: Colorectal cancer



CRD: Cysteine rich domain: extracellular distal domain on DR4/5, DcR1&2 etc.



CRE: cAMP response element



CREATININE: MW 113.12, is effectively insoluble in water, requiring 0.1 M Hydrochloric acid to dissolve. The quantification of this breakdown product from (chiefly) muscle and released into biological fluids was initiated by the German Jaffé (1886), using an alkalinized picric acid method (pH~12.5), which results in a colour change which can be measured (with attention to timing & temperature). Whilst convenient, it is not very specific, with carbonyl compounds, dopamine (appreciable elevation), cephalosporins and bilirubin interfering (in particular, when at 'usual' therapeutic dose levels, with ascorbic acid having a mild increase) and so, various modifications have been tried, seeking to perfect the method for the 'true creatinine' test; several methods are enzyme-based, with one using the creatininase (EC3.5.2.10) to form creatine, which is then converted by creatinase (EC3.5.3.3) to sarcosine + urea, the sarcosine then being converted by sarcosine oxidase (EC1.5.3.1) to glycine + H2O2 + CH2O, with chromophores added to indicate one or other of the reaction products; these quantifications may also be subject to interference, with bilirubin, creatine, dopamine, ascorbic acid & sarcosine causing interference; those producing H2O2 (an oxidizing agent) for detection would seem particularly vulnerable to a carry-over interference by the reducing (anti-oxidant) ascorbic acid; one method with ascorbate oxidase in the reagent still showed some interference using an enzymatic method; most of the non-creatinine 'chromogen' problem relates to serum/plasma – urine chromogens may account to ~3% of the total Jaffé-derived reading; there may be better methods now.

The serum/plasma Creatinine level is a standard test for renal function, rising as declining kidney function is unable to excrete it adequately through the kidneys; urinary creatinine over 24 h should remain relatively constant, so that determinations of it on 'spot test' specimens provides a measure of urinary dilution enabling comparisons between specimens for other analytes.

Patients who have therapies that include high dose ascorbate/ascorbic acid (Vitamin C) intravenously may have very large amounts excreted in the urine, to a level unanticipated by those who studied the more typical therapeutic levels meaning, that, without a special step to remove it, the enzymatic test results will be quite unacceptable and the Jaffé-based tests also probably unreliable.

Apart from declining renal function, pathological causes for actual serum creatinine level increases include the use of ACE inhibitors &/or angiotensin II receptor antagonist



CREB: cAMP response element binding protein; a regulator of genes; a consensus sequence of TGACGTCA. It is activated by phosphorylation through protein kinases including cAMP-dependent PKA, Calcium/calmodulin dependent kinase, GSK-3 & MAPK



CRESOL: Can open RyR channels



CRINOPHAGY: The autophagic removal of Golgi components



CRK II: Involved in mammalian engulfment of apoptotic cells; homologue of CED-2 of C. elegans



CRLR: Calcitonin receptor-like receptor



Crm1: Chromosome region maintenance 1; Exportin; H2O2 stimulates complexing with HMGB1



CrmA: Cytokine response modifier A; member of a large family of serpins, mainly found intracellularly. Blocks Fas-induced apoptosis by inhibiting active Caspase-8 & -10; See PI19



CRMP1: Collapsin response mediator protein 1

CRMP2:



CROSS PRESENTATION: See cross priming



CROSS-PRIMING: The presentation, by APCs, of 'exogenous' peptides by means of MHC class I  (typically MHC class II would be involved, for CD4+ activation). It can induce tolerance. This process is limited to bone marrow-derived APCs. Presence of CD4+cells is necessary.



CRP: C reactive protein. See IL-6



CRP: Cysteine-rich protein family, main being CRP1, 2, & 3/MLP. Highly conserved, associated with myogenesis. Share two tandemly-arranged LIM domains which may have protein-binding interfaces for proteins involved if differentiation. All three can interact with α-actinin and zyxin, cytoskeletal proteins. Expression seem associated with differentiation (expression decreased or is lost with transformation)



CRPC: Castration-resistant prostate cancer



CRT: (a) β-Catenin-Tcf-regulated transcription

(b) Calreticulin; involved with calcium binding and the endoplasmic reticulum; a tumour rejection antigen (interacting with CD91) and chaperone, involved in APC activation and antigen-presentation; it has no transmembrane domain, associating with LRP for signal transduction and acting as a receptor for the collagenous tail regions of MBL, SP-A, SP-D, conglutinin and C1q; its cell surface exposure after chemotherapy is caused by the ER stress response



CRUMBS: Forms a complex with Pals-1, Stardust/PATJ/Discs lost; assists defining the apical polarity



CRYOPYRIN: See NLR/NALP3



CS: (a) Contact site (eg immune synapse)

(b) Chondroitin sulphate; both MT3-MMP & pro-MMP2 bind to CS, but optimal binding depends upon the specificity of disaccharide units & the sulphation pattern (eg C4S)

(c) Cerebellar symptom



C4S: Chondroitin 4-sulphate; enhances MT3-MMP-mediated activation of pro-MMP-2

C6S: Chondroitin 6-sulphate; does not enhance MT3-MMP function



Cs+: Ion of Caesium. Atomic weight (12C) = 132.905; Ionic Radius = 1.69 Å; used as a charge carrier in some studies of Ca2+ channels



CSA: (a) Cockayne's Syndrome

(b) Colony stimulating activity



CsA: Cyclosporin A. A powerful immune suppressor



CSAIDS: MAPK14; p38 MAPK



CSC: (a) Cancer stem cell; cancer cells with self renewal and pleuripotency, similar to the stem cells in non-malignant tissue. There is a growing belief that most, if not all cancers and their metastases have CSCs. In addition to their self renewal, they provide progeny that lose some of the stem cell features and become transit amplifying cells, on the path to differentiation (as far as the tumour allows)

(b) cigarette smoke condensate



CSD: Conserved scaffolding domain (of caveolin1)



CSE: Chronic cigarette smoke exposure



CSE1L: Chromosome segregation 1-like



CSEP: Cortical somatosensory evoked potential



CSF: a) Cerebrospinal fluid

b) Colony stimulating factor - see G-CSF & GM-CSF

c) Cytostatic factor (in embryology - it halts progress at the second metaphase of meiosis, and may be suppressed by a calcium rise at fertilization, allowing preparation for cytokinesis)



CSGAG: Chondroitin sulphate glycosaminoglycan



CSHB: Chronic severe hepatitis B



Csk: (a) Tyrosine kinase that phosphorylates p56lck, itself phosphorylated by cAMP-controlled PKA

(b) C-terminal Src kinase; targets 'classical' rafts, but not 'heavy rafts' or non-raft membrane



CSL: CBF1-Su(H)-Lag-2; a transcription activation complex associated with Notch signalling



CSM: Complete synthetic medium



c-SMAC: Central part of SMAC, with lipid rafts, CD3/TCR/co-stimulatory



CSP-α: Centrosomal protein-α; appears at mitosis - function unclear



CSP: (a) Cysteine string protein. A protein associated with regulated secretory organelles. CSPα is an abundant synaptic vesicle protein that contains a DNA-J domain characteristic of Hsp40-type co-chaperones. Tonically active ribbon synapses in retina are particularly sensitive to the deletion of CSα, leading to early neuro-degeneration. The cochlear hair cells have CSPβ, and are unaffected

(b) Cell surface peptidase



CSPG: Chondroitin sulphate proteoglycan; (CSPG3, neurocan) - see MCSP and Chondroitin sulphate



CSQ: Calsequestrin; inhibits the RyR Ca2+ channel, allowing Ca2+ through the channel maximally when at >5 mM Ca2+



CSR: (a) Class switch recombination; process in B-cell stimulation response, regulated by T cells, follicular dendritic cells (& others)

(b) Composite sulphated regions; the sulphated domains and adjacent intermediate transition zone regions of partial sulphation in the heparan sulphate chains.



C-SRC: A mammalian proto-oncogene



CST: CMP-sialic acid transporter; predicted to have 10 transmembrane domains, with both ends in the cytosol and forming an hydrophilic channel with glycine residues; Tyrosine is important in specific binding to the Sia



C4ST: Gene for chondroitin-4-sulphotransferase



CT: (a) Cholera toxin. An adenylate cyclase activator that increases cAMP levels

CTβ: Marker for lipid rafts & endocytosis

(b) Calcitonin



CT26: A murine colon cancer cell line; sensitive to Taxol



C-Tak1: Cdc25C-associated protein kinase. Phosphorylates Ser216



CTAL: Cortical thick ascending limb (renal)



CTAP-III: Connective tissue activating peptide III - see HPSE



CTβ/CTB: Cholera toxin β subunit; binds to Gangioside GM1 (indicating lipid rafts); endocytosed via lipid rafts & makes an endocytic marker;



CtBP1: Transcriptional co-repressor seen in the nuclear layers of the retina



CtBP1/BARS: (COOH-terminal binding protein 1/Brefeldin A adenosine diphosphate ribosylated substrate of 50 kDa), a protein that has previously been identified as a transcription co-repressor and Golgi-localized membrane-fissioning  protein. A RIBEYE homologue. May be involved in presynaptic vesicle trafficking.



CtBP2: Transcriptional co-repressor seen in the nuclear layers of the retina



CtBP3: See CtBP1/BARS



CTC: Common Toxicity Criteria



CTCL: Cutaneous T-cell lymphoma



Ctec/cTEC: Cortical thymic epithelial cells; characterized by EpCAM1 & Ly51



CTES: Clusters of thymic epithelial staining



CTF: C-terminal fragment; the -COOH terminus of a peptide



CTGF: Connective tissue growth factor; See CCN2



CTL: (a) Cytotoxic T lymphocyte; usually CD8+ CD28- ; develop granules with perforin and Granzyme, which they exocytose into target cells, stimulating cell death. Action against Ag+ B lymphocytes is rapid, ~10 min, which is necessary because the cell apposition time is usually less than 30 min, ~10 min, 95% less than 30 min. Treg cause the exocytosis to fail. Treg CTL lysis inhibition seems to be dependent upon the sustained presence of Tregs, TGF-β and one or more other factors

(b) CTL: C-type lectin; important for fungal recognition; (see PRR)



CTLA: (CD152) Cytoplasmic T lymphocyte associated antigen CTLA-4: A marker for negative regulatory CD4 T cells; homologue of CD28; can oppose and also synergize. It is intracytoplasmic, coming to the cell surface after receptor activation, showing greater affinity than CD28, whereupon it acts as a negative factor. Its low levels in CD4 CD25- cells may be more because of destruction



CTLL-2: A murine cell line that responds to muL-2



CTLP: Cytotoxic T lymphocyte precursor



CTMP: C-terminal modulator protein



CTNNB1: Gene for β-catenin



CTV: Clinical target volume; the volume considered clinically relevant for targeting radiotherapy



CTX: Cholera toxin subunit B; binds to cell surface Ganglioside GM1 and internalized mainly by caveolae



Cu2+: Copper ion; can bind with the first 4 amino acids of the N-terminus of Albumin (Asp-Ala-His-Lys)



CUBILIN: One of a pair making a tandem receptor on the renal proximal tubular cells; involved in the endocytosis of peptides (eg light chains). See Megalin



CUBITUS INERRUPTUS (Ci): Transcription factor in Drosophila. See Hedgehog



CUCURBITACIN: An inhibitor of STAT3 activation



CUL: See Cullin



CULLIN: Scaffold proteins

Cul1: involved with NEDD8 and E1-3 in the process of neddylation in Hh signalling

Cul3: with Keap1, is involved in the ubiquitination and proteasomal degradation of Nrf2, preventing the latter from entering the nucleus and affecting transcription



CUMENE HYDROPEROXIDE: An aromatic, lipophilic peroxide, formed as an intermediary in the industrial production of acetone and phenol from benzene and propylene; having a benzene ring and one side-chain. When included in an intravenous infusion, it may cause irritation of the veins. When applied to PC12 cells in vitro at 50-100 μM, there is cell rounding and detachment over the first hour; by 3 h, ~80% are dead, but ~15% remain attached & seem resistant. Potency, compared to H2O2,is ~ x 10



CUMULUS CELLS: The mass of cells that surrounds the ovum/oocyte. It persists after ovulation. In the mouse, each ovum has ~ 2,000 cumulus cells in association. They can metabolize Glucose at 1 mM with Lactate 3 mM to produce Pyruvate as though Glucose of 5.56 mM were present with the Lactate, but handle 1 mM Glucose alone poorly. Production of Pyruvate under in vivo conditions is probably x 4.5 basic levels. They are rich in GSH; H2O2 is ~undetectable.



CUPIN METALLOENZYME: Family of regulators of chromatin structure; highly conserved



CUPRIZONE: Copper chelator, which causes abnormal dimerization of mitochondrial DNA and reduce mitochondrial respiration; toxic to oligodendrocytes, and others outside the brain. Necrosis of oligodendrocytes started within 2-3 week (of just sub-lethal intake), with demyelination follows at 4-5 week - reversible. At lower doses, with longer interval, the inner cytoplasmic tongues of the oligodendrocyte extensions deteriorated



CURCUMIN: Diferuloylmethane (from Turmeric); natural phenolic compound, a potent anti-tumour, anti-inflammatory and anti-oxidant and free radical scavenger, that induces apoptosis, inhibits PKC and said to inhibit Syk; has easy cell penetration, accumulating on membranes; inhibits HAT; reported to reduce the numbers of colon cancer stem cells (CD44+ & CD166+) after FOLFOX failure; is poorly soluble and unstable in water, reducing its bioavailability; binds with proteins; considered to be relatively non-toxic to endothelial cells; analogues show variable attributes, some better, some less, than curcumin; inhibits ACE, Tyrosinase & HIV protease; inhibits function of Integrin α6β4, NF-κB, decreases HER2 oncoprotein, reduces phosphorylation of Akt & MAPK and VEGF; said to be ameliorate immune suppression and inhibits systemic toxicity in those with tumours; reduces proliferation & induces apoptosis in HT29 colon cancer cells via Caspases -3 & -12 (not -9), also involving calpain



CURCURBITACIN: A STAT3 inhibitor



CUX-1: A transcription factor that regulates (with differences) the activities of TNF & IL-6 promoters



C-VAMP: Chemotherapeutic protocol for multiple myeloma; cyclophosphamide, vincristine, Adriamycin (doxorubicin) and prednisolone



CVD: Cardiovascular disease



CVID: Common variable immune deficiency; there may be a failure of CD20 to dissociate from the BCR, thereby diminishing Ca2+ influx; defect in this condition may be the failure of the link between the BCR & CD20 to break, the BCR then fails to be endocytosed



CVM: Complex vertebral malformation; A recessive genetic condition of cattle, having mutation of the UDP-GlcNAc transporter gene



Cx: (a) Cervix uteri

(b) Connexin protein; a part of a gap junction



CX2: Colon cancer cell line



CXCL: Series

CXCL1 Gro1

CX3CL1 fractalkine; 373 aa, expressed on endothelial cells

CX3CR1 Fractalkine receptor; 7 transmembrane domains, to GTP-binding proteins. Expressed on monocytes & cytotoxic lymphocytes

CXCL3 MIP-2

CXCL4 PF4

CXCL8 IL-8

CXCL9 Mig

CXCL10 IP-10, IFN-γ inducible 10 kDa protein; receptor CXCR3

CXCL12α SDF1α: Chemokine stroma-derived factor 1α. Expressed by a large range of tissues; in the marrow, by stromal cells, osteoblasts and endothelial cells, stimulating progenitors in vitro, but inhibiting them in vivo. Stimulates chemotaxis and proliferation. It may facilitate IL-7 and/or IL-3 activation of ALL cells, possibly involving phosphorylation of ERK1/2 & Akt.

CXCL13 BCA-1; necessary for B lymphocytes (BLC)



CXCR4: Receptor for SDF-1, stimulating migration and metastasis in breast, ovarian and SCLC. It is expressed by endothelial cells. It, and its ligand, seem important for the integrity of the marrow stem cell niches. See SDF-1. It is an entry co-receptor for strains of the HIV-1 virus



Cy3: Indocarbocyanine

Cy5: Indodicarbocyanine



CyB: Cyclin B



CYCLIN: Cyclin-dependent kinase (cdk) may link centrosome duplication with DNA replication in S phase. Cyclin B necessary for centrosomal recruitment of Eg5. Cyclin B1 Aberrations of Cyclin D & E common in cancer, also cdk4 & 6, and cdk inhibitors p16(INK4A) & p15(INK4B). A & B activate centriole separation. Control is largely by transcription factors.

Cyclin B1/Cdk1 accumulates on centrosomes in G2 and activates centrosome separation. Cyclin D1 associates with androgen receptors and is a co-repressor, but an activator of oestrogen receptor



CYCLOHEXIMIDE: 4-[(2R)-2-[(1S,3S,5S)-3,5-Dimethyl-2-oxocyclohexyl]-2-hydroxyethyl]piperidine-2,6-dione; antibiotic from Streptomyces griseus. Inhibits translation of protein precursors at the ribosomes in eukaryotes, and activates p38 MAPK; its action is rapid & reversible; does not affect mitochondrial translation



CYCLOPHILIN A: A DNase that links with AIF & γ-H2AX to degrade DNA in a form of non-caspase-dependent necroptosis

CYCLOPHILIN D: A mitochondrial matrix protein, probably involved with mPTP function; absence reduces oxidative stress-mediated necrosis, as well as from other forms of stress;



CYCLOPHOSPHAMIDE: An anti-neoplastic and anti-inflammatory drug. Splitting off the phosphate group in the target tissue releases an alkylating chemical. When used for MS, there is a decrease in CCR5 and CXCR3, and a rise of CXCR4 in the blood. It is used prior to marrow transplantations, apparently to stimulate chemokine production and release (mobilization)



CYCLOPIAZONIC ACID: From Penicillium cyclopium; an inhibitor of the sarcoplasmic reticulum Ca2+-pump, and reduces Ca2+-dependent K+ currents in muscle



CYCLOSPORIN: A powerful immune suppressant; inhibits NFAT and IL-2 transcription by blocking Calcineurin (which dephosphorylates NFAT, allowing its translocation to the nucleus)



CYLD: Cylindromatosis; deubiquitinase; see necroptosis



CYLINDROMATOSIS: A deubiquitylase; a regulator of necroptosis, counteracting ubiquination enzymes such as cIAP



CYP: Cytochrome P450 monooxigenase(s); eg CYP1A1, CYP1B1, CYP3A4; can be involved in the bioactivation of carcinogens (Phase I); See P450



CYP17: 17α-hydroxylase



CypA: Cyclophilin A



Cyr: Cysteine rich; eg Cyr61 = CCN1

CYR61: Cysteine-rich 61; See CCN1



CysQ: The E. coli pAp-phosphatase inhibited by Li+ & Ca2+



CYST (of bacteria): A differentiated structure that is resistant to desiccation &/or other mild/moderate chemical or physical assaults; they generally have a central body surrounded by a membrane-derived capsule; Clostridia and Bacilli are typical examples



CYSTATIN-B: Endogenous inhibitor of cysteine proteinases

CYSTATIN-C: A serum component, the measurement of which may provide a better indication of renal function than serum creatinine



CYSTINE KNOT SUPERFAMILY: Possess 10 cysteine amino acid residues forming ring with an extension into the ring; the consensus sequence is :

C1-(X)n-C2-X-G-X-C3-(X)n-C4-(X)n-C5-X-C6

. . . . . . . . < Part of ring > . . . . . . . . . . . . <Part of ring>

There are 10 or more members of the superfamily; they are formed intracellularly, with the knot preventing a globular structure; when expressed, they are extracellular proteins, interacting with specific receptors; the largest subfamily is the TGFβ family, with others being the PDGFs & GPHs. They have been classified into 3 subfamilies according to the size of the ring:
CAN family: 8 membered ring – 7 members, including Gremlin, PRDC & others
Twisted gastrulation: 9 membered ring
Noggin: 10 membered ring



Cyt-c: Cytochrome c; released after mitochondrial swelling, activates caspases & induces apoptosis



Cytip: A protein that down-grades the binding by LFA-1



CYTOCHALASIN B/D: Fungal alkaloid. Actin depolymerizing agent. Causes actin filaments in a cell to depolymerize, by binding the + end of F-actin: the cytoskeleton disappears. Cytochalasin B binds to glucose carriers and inhibits facilitated entry. It is used in embryology to prevent cell division and if added to cell cultures and the cells centrifuged on a coverslip with cell side down, the cytoplasts remain adherent to the coverslip and the karyoplasts are centrifuged down.



CYTOCHROME-c: Key component of mitochondria. Its release by members of apoptosis factors such as Bax & Bak allows it to bind to IP3R in the ER, which abolishes the Ca2+-induced inhibition of the channel and amplifies the Ca2+ release from the ER. This then induces Caspases leading to endonuclease production, DNA fragmentation and apoptosis. The reduction of Acetylated Cytochrome c is a measure of superoxide anion. In some situations, cytochrome-c is not released unless there is Cathepsin (B) activity



CYTOKERATIN: Component of epithelial cells - a marker



CYTOKINESIS: Cell division



CYTONEME: A fine cellular extension that can reach over many cell widths and may be used for signalling



CYTOPLASM: The cellular contents within the plasma membrane, but excluding the nucleus. See cytosol



CYTOPLASMIC CELL DEATH: Refer to necrosis & lysosomal cell death; large-scale spillage of the lysosomal contents can rapidly destroy the cell by necrosis



CYTOPLASMIC POLYADENYLATION: The addition, within the cytoplasm, of additional polyadenyl groups (A) to lengthen the poly(A) tail of mRNA. This can control the translational activation of the mRNA. Both the act of extending and the length may be important, the tails that invite polyadenylation have either Hexanucleotide AAUAAA, or AU-rich sequence eg UUUUUAU, which is termed the cytoplasmic polyadenylation element (CPE)



CYTOPLAST: Most of the cytoplasm of the cell that has been stripped-off the nucleus and its thin surrounding cytoplasm; anuclear cytoplasm



CYTOSKELETAL PROTEINS: Actin, tubulin, myosin, spectrin and β-catenin



CYTOSOL: The soluble cell content within the plasma membrane, excluding the nucleus and organelles. The main cytosolic electrolytes are typically :

K+ 100-140 mM

MgATP 5-10 mM

Na+ 10 mM

free ATP 400-600 μM

Cl- 5-70 mM

free Ca2+ 50-100 nM

free Mg2+ 1 mM

+ assorted proteins etc.

CYTOVILLIN 2: See Ezrin



CZB: Chatot-Ziomek-Bavister; a basic culture medium for mouse embryos developed in Ziomek's laboratory



D: Diversity (as relates to antigen-receptor genes for immunoglobulins)

2D: Two dimension

32D: A stem cell progenitor that can differentiate into the granulopoiesis lineage, given the right stimulation. Notch1 inhibits this change



D1: A well characterized DC from the murine spleen. It is normally immature and is growth factor dependent, becoming activated & mature with LPS &/or TNF-α



61D3: A monoclonal antibody against the phosphatidylserine receptor of macrophages



D6: Non-signalling chemokine receptor; may control the movement of chemokines in association with barriers. It is expressed by lymphatic endothelium, binding and internalizing CC chemokines, possibly limiting inflammatory responses (See DARC)



DAAM1: Protein that links Dsh to Rho (see Wnt)



DAB: Diaminobenzidine. It is permeable to cells and when presented with H2O2 to cells in which horseradish peroxidase had been applied, polymerizes in the HRP-containing compartments. Surrounding structures can be dissolved away, and the resultant cast examined (eg by EM)



DAB2: A protein with a phosphotyrosine-binding domain; involved in clathrin function



DACHSOUS-1: Huge cadherin-related protein



DADLE: [D-Ala(2), D-Leu(5)]-Enkephalin - a stable delta opioid peptide



DAF-16: Insulin regulated transcription factor



DAG: Diacylglycerol; can activate TRPC3/PKCβ



DAI: DNA-dependent activator of interferon regulatory factor; a pattern recognition receptor, that activates the transcription factors IRF3 and NF-κB. DAI associates with TBK1; has a RHIM-mediated interaction with RIPK1 & RIPK3



Dally: Division abnormally delayed. Gene for a Glypican proteoglycan in Drosophila; affects Wingless (Wg) and Decapentaplegic (Dpp) with some tissue-specific control by HSPGs. It may stabilize Dpp on the surface on contacting cells, its range being only about one cell's width. This may be important in the commitment and function of stem cells and their niches



DAMP: (a) 3-(2,4-dinitroanilino)-3'-amino-N-methylpropylamine; used in EM studies to identify the acidic organelles such as lysosomes

(b) Damage-associated molecular pattern (molecules) (eg HMGB1); involved in cell proliferation and inflammation; bind to PRRs; some actions can be beneficial (eg after brain/cord injury and ischaemia in mice, where TLR2 may be involved)



DAN: Differential screening-selected gene abberative in neuroblastoma



DANK1 & 2: Two genes for ankyrin in D. melanogaster



DANSYL AMIDE: 5-(Dimethylamino)naphthalene-1-sulfonamide



DANTROLENE: A A RyR antagonist



DAPI: Dilactate; 4',6-Diamino-2-phenylindole, dilactate. Stain to detect and demonstrate single nucleic acid molecules. Very sensitive. Used to demonstrate apoptosis, demonstrating chromatin clumping. Fluoresces deep blue under UV



DAPK: Death-associated protein kinase; phosphorylates & thereby modifies function of beclin-1; can be activated by ERK



DAPPER: An inhibitor of Dishevelled (originally isolated from Xenopus; human hDPR1); see Wnt/β-catenin



DARC: Duffy antigen receptor for chemokines; 338 aa & 7 transmembrane domains. Non-signalling chemokine receptor; may control the movement of chemokines in association with barriers. It is expressed by RBCs and endothelial cells and binds both CC and CSC chemokines



DARPins: Designed ANK repeat proteins



Das-1: Marker for colonic mucus



DASATINIB: A second generation tyrosine kinase inhibitor (see Imatinib). It can produce cutaneous reactions



DAT: Dopamine transporter



DAUDI: B-cell lymphoblastoid cell line from Burkitt's lymphoma, EBV+



Daxx: Death domain-associated protein gene



Daxx: Protein involved in chromatin remodelling; absence is associated with a poor prognosis with some cancers



DBA: Diamond-Blackfan anaemia; there are mutations of the ribosomal proteins



DBD: DNA-binding domain



dbEST: Database of expression sequence tags



DBH: Debromohymenialdisone. Inhibits checkpoint kinases Chk1 & 2



DBL: See GEF



DBP: DEAD-Box protein



DBS: See GEF



DC: (a) Dendritic cell

DC1: Monocytic morphology/myeloid (M-DC); express CD13, CD33, CD11c, ILT1, CD123low & capacity to produce large amounts of IL-12

DC2: Plasmacytoid dendritic cells - from plasmacytoid T cells (P-DC); no myeloid markers, ILT3R, CD62R, CD123 & secrete high amounts of IFN-α

(b) Dyskeratosis congenita



DCA: Dichloroacetate sodium; may unblock the pyruvate pathway to mitochondria. See Warburg effect. It seems to have an anticancer effect at low toxicity, with some positive response quoted at 60 - 70%



DCAMKL-1: A cell surface marker for stem cell characteristics



DCC: Deleted in colon carcinoma; receptor for the axon chemoattractant and chemorepellent Netrin-1; without Netrin-1, DCC forms a complex with Caspase-9 & Caspase-3 causing Caspase-mediated apoptosis



DCE: Dynamic, contrast enhanced (eg MRI)



DCF: 2',7'-Dihydrodichlorofluorescein, the oxidized product of DCFHDA



DC-3F: A transformed Chinese hamster lung fibroblast cell line





DCFHDA: Dichlorodihydrofluoresceine diacetate; used for measuring intracellular reactive oxygen species (fluorescent)



DC-HIL: Dendritic cell-associated heparin sulphate proteoglycan-dependant integrin ligand; 574 aa; a transmembrane protein expressed on APC, including DCs, epidermal Langerhans cells and macrophages; heavily glycosylated; has an Ig-like domain and a KRFR that binds heparin/heparan, also integrin by its RGD motif: identified as ligand of Syndecan-4. It is immune suppressant, involving CD148 to inhibit T-cell activation distal to the synapse



DCHS1: See Dachsous-1



DCIP: 2,6 Dichloroindophenol. See Diaphorase



DCIR: Dendritic cell immunoreceptor; involved with HIV-1 ligation



DCIS: Ductal carcinoma in situ; usually used in reference to breast carcinoma, but also others



DCL-4: Dicer-like 4



DCM: Dilated cardiomyopathy; See Lamin



DC-PCR: Digestion-circularization PCR



DCR1: Dicer 1; see Dicer

DCR-2: Dicer 2; see Dicer



DcR1: Transmembrane decoy receptor 1; See TRAIL-R3

DcR2: Transmembrane receptor 2; See TRAIL-R4

DcR3: Decoy receptor 3; See TRAIL-R3; a soluble receptor and member of the TNFR superfamily; its expression in cancer patients is correlated with poor survival, possibly related to activation of tumour-associated macrophages



DC-SIGN: (Dendritic cell-specific intercellular adhesion molecule 3 grabbing non-integrin.) Homotetrameric type II membrane protein belonging to the C-type mannose-binding lectin family; has a C-terminal extracellular calcium dependent carbohydrate recognition domain; antigen receptor and an adhesion molecule associated with DCs (inhibited by mannan). DC-SIGN+ DCs are in the human thymic cortex (occasionally the cortico-medulla), not the medulla



DCT: Distal convoluted tubule (renal)



DCX: Doublecortin, a MAP in photoreceptors



DD: (a) See Death Domain

(b) Double dull (CD4lo CD8lo). Some of these can succeed in positive selection and may go on to become CD4+CD8lo, then to SP



DDAO-SE: 7-hydroxy-9H-(1,3-dichloro-9,9-dimethylacridin-2-one)-succinimidyl ester; A fluorescent marker that can be used to assess cell proliferation by its dilution



DDB1: Damaged DNA binding protein 1, an E3 ubiquitin ligase



ddit3: DNA damage-inducible transcript 3. See under CHOP



DDR1 & 2: Discoidin domain receptor-1 (a-e; DDR1d & e are kinase dead) & 2; activated by tyrosine phosphorylation; RTKs with slow activation kinetics; bind to collagen. Collagen stimulates dimerization and phosphorylation by DDR1 + Wnt 5a, inhibited by GPCR blockers (Pertussis). Wnt/catenin pathway is not involved with discoidin/breast cells. DDR1 is largely restricted to epithelial cells (lung, breast, brain, kidney and GI, whereas DDR2 is expressed by stromal cells. Female mice deficient in DDR1, have defective mammary gland branching development. Wnt + collagen stimulate phosphorylation of DDR1



DEAD-BOX: The largest protein family of superfamily 2 (SF2) RNA helicases; the helicase core has 2 RecA-like domains and common sequence motifs which, in the case of the DEAD-Box family, spell-out the aa sequence; many catalyse ATP-dependant unwinding of RNA duplexes or remodelling RNP complexes



DEATH (cell): See under Apoptosis &/or Cell Death



DEATH DOMAIN (DD): Receptor domains ~80 aa long which, when united with other similar DDs on other proteins of the message series, activate the cascade; an important example is TNFR1, which binds to TRADD (TNFR2 lacks the DD)



DEATH RECEPTOR (DR): Series of receptors for TRAIL :

DR4/TRAILR-1

DR5/TRICK-2/KILLER/TRAIL-R



DEB: Dystrophic Epidermolysis bullosa



DEC205: A marker for mature lymphoid DC; can introduce antigens to both MHC class I & II loading compartments, thereby activating both CD4+
(to assist) and CD8+ (to effect) cells



DECORIN: A small CS/DS structural proteoglycan of the cornea; the xylose in the linker of the GAG chain may be transiently
phosphorylated during formation; an important modulator of TGF-β function



DECOY RECEPTOR(S) 1 & 2:

DcR1/LIT/TRID/TRAILR-3: has no Death Domain

DcR2/TRUNDD/TRAILR-4: truncated/inactive DD may interfere with the binding of TRAIL to DR4/5



DECTIN: A C-type lectin receptor; a major β-glucan receptor; can be involved in fungal infections; Dectin-1 can trigger a pro-IL-1β by an extracellular-derived non-canonical caspase-8 inflammasome



DED: Death effector domains (eg of FADD, mediates recruitment & activation of pro-Caspase-8, releasing p19/p12 fragments)



DED PROTEINS: Death effect domain; the N-terminal sequence of FADD; Procaspase-8 & cFLIP bind to the DED, forming a death-inducing signal complex (DISC); may trigger Caspase activation for apoptosis



DEF: Desferrioxamine; Fe2+ chelator



δEF1/ZEB1: Transcription factor, increased in diffuse gastric cancers, with decreased E-cadherin



DEFENSINS: Antimicrobiol peptides important in innate mucosal immunity. However, human defensins 5 & 6 promote HIV infectivity. See also HD5 - 6



DEGENERATE TCR: The ability of the flexible end of the TCR to combine specifically with a number of peptide/MHC complexes by spatial adjustment ~
poly-specific inter-changeability. Some p/MHC-TCR combinations may be weak, and not result in negative selection



DEG/ENaC: Degenerin/epithelial Na+ channel superfamily



DEGUELIN: A Rotenoid isolated from the African plant Mundulea sericea that shows anti-cancer effects, particularly against head and neck squamous cell cancers. It may act by suppressing PI3K/Akt and NF-κB, inhibition of suppression, XIAP and HSP90 (binding to the ATP-binding pocket)



DEL-1: Homologous to MFG-E8, produced by BAM3, a macrophage line



DELAMINATION: The separation of a layer of cells from an established group



DELTA1 : Transmembrane ligand that bind with Notch



DELTA-LIKE 3: Transmembrane ligand that binds with Notch



DELTEX: A cytoplasmic zinc-finger-containing protein; involved with Notch signalling (a minor pathway). It does not move to the nucleus, but interacts
with Grb2 to influence the JNK pathway



DEM: Diethylmaleate; removes GSH from cells; oxidizing



DEMECOLCINE: ('Colcemid'); N-Deacetyl-N-methylcolchicine; used to arrest cell in culture at metaphase.



DENDRITIC CELLS: (DRC-1+); Primitive immune cell with few surface markers, very heterogeneous: expressing adhesive molecules, CD11c, CD15s, CD18, CD29, CD44, CD49d, CD50 and CD54, with MHC class II and co-stimulatory CD83, CD40, CD80 and CD86. Originate from bone marrow precursors CD34+, play an essential role in the thymus, reside in skin and move into circulation, where found in very small numbers. Distinctive appearance. Myeloid are generally immunogenic; lymphoid are tolerogenic; (subcutaneous injections of pulsed murine bone marrow DCs home to the regional nodes and are more effective against subcutaneous tumours nearby). Mice have a plasmacytoid pre-DC in the first weeks of thymus development, with innate activity. There seem to be two types, the probable lymphoid CD8α+ Mac-1- DEC-205+, the probable myeloid being CD8α- Mac-1+ DEC-205-; the spleen has both, the thymus, the lymphoid line only.  Potent antigen-presenting cells, expressing high levels of MHC class II products. GM-CSF stimulates. When pulsed with breast cancer antigens and co-cultured with T cells, cytokines IL-12 and IFN-α were produced. Maturation and infiltration are inhibited by VEGF.

Tumours in rat/mice models produce one or more factors that 'license' immature DCs (CD11c+ CD11b+ co-stimulatory) to produce TGF-β. This, plus MHC Class II + peptide (specific; or anti-CD3 antibody) stimulates the proliferation of Treg, to reduce host rejection of the tumour.

Present as <1% of human PBMC, usually characterized by non lineage markers (Lin-) and HLA-DRhi: representing precursors of myeloid (CD11c+) in transit &/or antigen-captured, in transit from periphery to lymph nodes. The human thymus: 65% are CD11b- CD33lo CD45lo (lymphoid-related, IL-12 secreting), with 35% CD11b+ CD33hi CD45hi (myeloid-related). GM-CSF is the major stimulant for myeloid DCs; for humans the addition of IL-4 &/or IL-13 is necessary; these have the characteristics of 'inflammatory' DC or Tip-DC. Those stimulated in vitro by Flt3L are more akin to the lymphoid tissue resident DC subtypes.

Plasmacytoid DCs (pDC), able to secrete Type 1 IFN in response to viral infections, are probably coming from bone marrow-derived lymphoid precursors.

Dendritic cells employ the αvβ5 vitronectin receptor to recognize apoptotic cells, but they may be inefficient at presenting the peptides and may involve delayed clearance.

Interdigitating DC

Mac-1-, -2+, -3+, Ia+, ATPase+

Follicular DC

Mac-1-, -2-, -3-, Ia-, ATPase-, FcR+

Lymphoid DC

Mac-1-, Ia+, ATPase-, FcR-

Kupffer

Mac-1-, -2+, -3+, Ia+, FcR+

Macrophage

Mac-1+, -2+, -3+, Ia+/-, ATPase+, FcR+



DENILEUKIN DIFTITOX: Cell binding domain of Diphtheria toxin; targets and kills activated T cells with receptors for IL-2



DENOSUMAB: A monoclonal antibody against RANKL



DENV: Dengue virus



DEOXYSPERGUALIN: An immune suppressor (see LF 15-0195)



DEP: Dishevelled, Egl-10, Pleckstring. Combines with cAMP and is responsible for location to the plasma membrane.



DEPC: Diethyl pyrocarbonate. Perturbs Histidine function in enzymes



DEPOTENTIATION: A term used in relation to CRAC channels, where the incoming ion current declines with time



DERMATAN SULPHATE: = Chondroitin sulphate B; the GlcA of Chondroitin sulphate is converted by epimerase to IdoA



DESFEROXAMINE: An iron chelator, sequestering iron so that it is catalytically inactive as far as ascorbate in concerned; hydrophilic, yet cell permeable, able, in the short term, to access endosomal or membrane iron



DESIPRAMINE: Inhibitor of aSMase



DESMOPLAKIN: Occupies the inner dense plaque of the desmosome and tethers to the intermediate fibres



DESMOSOME: An ordered point of contact between adjacent cells (cf adherens junction & tight junction). Intracellular components include desmoplakin, plakoglobin, plakophillin and the cytoplasmic processes of the desmosomal cadherens (desmoglein & desmocollin). Plakoglobin probably provides a template, on which desmosomal cadherens cluster at the cell surface. Tethering to the intermediate filaments is by the desmoplakin C-terminus



DEUTERIUM: Hydrogen isotope with the nucleus containing one proton and one neutron; water containing it (deuterium oxide, 2H2O, 'heavy water') is toxic to many biological systems; said to stabilize labile proteins; the deuterium oxide inhibits HSP induction (possibly by protein stabilization)



DEUTEROSOME: A large, non-membranous electron-dense spherical structure about 75-400 nm in diameter, with a corona. Involved in
Ciliogenesis (see latter and fibrous granule). They are believed to be formed from fibrous granules and may be the nidus for basal body formation.



DEVD: Aspartate-Glutamate-Valine-Aspartate; amino acid sequence common to many enzymes in the apoptosis cascade; cleaved by Caspase-3-like proteases



DEVDase: and enzyme that degrades DEVD



DEX: (a) DC derived exosome

(b) Dexamethasone

(c) Dextrose = D-glucose



'DexD/H-Box': Proteins related to DEAD-Box



DFMO: Difluoromethyl ornithine; best known for the treatment of West African Trypanosomiasis; increases the number of GlcNH3+ in Heparan sulphate - sites for deaminative cleavage catalysed by NO, generating anhydromannose-containing degradation products. The sites induced are more widespread than near the core protein



DFO: Desferoxamine; a chelator for iron overload; hydrophilic, but cell-permeable



DG: (a) Diacylglycerol (See DAG)

(b) 1,2-Didecanoylglycerol (1,2-Dicaprin); cell permeable activator of protein kinase C in platelets



2-DG: 2-Deoxyglucose. Similar to glucose, but cannot be metabolized past Hexokinase



DGC: Dystrophin-glycoprotein complex; absent from the plasma membrane of those with Duchenne muscular dystrophy



DGCR8: Di George syndrome critical region 8; a partner for Drosha; the core may recognize pri-mRNAs in two orientations



Dgrip: Family of proteins isolated from Drosophila, related to the γ-TuRCs of the centrosomes. Dgrip84 & 91 seem to associated with γ-Tubulins to form the γ-TuSC at the negative end of the microtubule. Dgrips 163, 128 and 75s are found in a cluster further from the end of the microtubule and may stabilize the ring structure and attach it to the centrosome.



DHA: (a) Docosahexaenoic acid; found in brain and synaptic membranes. Retained when there is starvation for n-3 fatty acids. It is involved in Zellweger's
syndrome, and recycles like arachidonic acid. Lithium does not affect.

(b) Dehydroascorbate; normally found in food and absorbed by the GLUT system, with the plasma levels very low and a half-life of 5 – 15 min; Glut-mediated DHA uptake (rapid - minutes) seems restricted to specialized oxidizing conditions, as with activated neutrophils in inflammation and possibly around cancers; formed extracellularly when ascorbate is oxidized to H2O2, and it is taken up by the tumour cells by the GLUT transporters, after which it is reduced to ascorbate by GSH or glutaredoxin in the cytoplasm. It hydrolyses to 2,3-DKG or L-erythrulose & oxalate. Cell culture experiments indicate that cancer cells appear less sensitive to DHA than to ascorbate (with little correlation)



DHAP: Dihydroxyacetone phosphate



DHC: Dihydrocalcein



DHE: Dihydroethidium; upon interaction with superoxide, DHE yields ethidium bromide and yields a red fluorescence



DHEA: Dehydroepiandrosterone; an hormone from the adrenal cortex, also inhibitor of G-6-PD



DHF: Dengue haemorrhagic fever. A poorly defined complication of Dengue Fever, marked by a positive tourniquet test and haemorrhages due to
endothelial damage, possibly by cytokines, usually in patients with a second Dengue infection



Dhh: Dessert; Hedgehog ligand



D-HicDH: D-Hydroxyisocaprioate dehydrogenase. One of the D-2-Hydroxycarboxylate dehydrogenases (as is GAPDH)



DHLA: The reduced form of α-lipoic acid (see the latter)



DHODH: Dihydroorotate dehydrogenase; the rate-limiting enzyme in the pyrimidine synthesis pathway; expression down-regulated by doxorubicin; inhibited by brequinar;



DHPR: Dihydropyridine receptor; L-type Ca2+ channel



DHX9: Human RNA helicase A



DI: Deformability index



DIA1: Assists RhoA maintain E-cadherin mediated adhesion



DIABLO: (Smac) Direct inhibitor of apoptosis-binding protein with a low isoelectric point. Mitochondrial component released by the effects of Bid, Bak and
Bax. Inhibitor of IAP in the Cytochrome C/Apaf-1/Caspase-9 pathway; unlike HtrA2, it is not a serine protease



DIACYLGLYCEROL (1,2-DAG): Second messenger. Stimulates protein kinase C



DIAMIDE: [Diazenedicarboxylic acid bis(N,N-dimethylamide)]; cell-permeable; causes thiol oxidation (reversible), especially of GSH. It causes an
increase in Ca
2+ oscillations & elevates cytosolic Ca2+. The reaction with GSH produces GSSH & a hydrazine of diamide



DIAMINOBENZIDINE: A chromagen for avidin-biotin immunological decoration of cells



DIAPHORASE: Enzyme; NADH:DCIP oxidoreductase. Uses 1,6 Dichloroindophenol (DCIP) as substrate



DiBac4(3): Anionic oxonol dye; a molecular probe for assessing the voltage across the plasma membrane 



DIC: (a) Differential interference contrast – microscopy

(b) Disseminated intravascular coagulation



DICER: A microRNA-generating enzyme; 217 kDa multidomain enzyme that probably accepts pre-microRNA substrate of nuclear origin from Exportin-5; recognizes pre-microRNA by its central PIWI/Argonaute/Zwille domain, processing the pre-microRNA to microRNA by C-terminal RNase IIIa & IIIb motifs; forms a complex with TAR RNA-binding protein & KSRP and acts as a key enzyme complex for pre-microRNA; acts with Ago2  downstream and transfers split products to fragile X mental retardation protein; binds with CLIMP-63 with minimum 242-430 aa, a site that may be used by TRBP2 (electrostatic & mutual exclusion); has subtypes:

Dicer1 (Dcr1) is mainly involved in miRNA biosynthesis in Drosophila melanogaster
Dicer2 (Dcr2) required for dsRNA processing for siRNA/RNAi (Drosophila melanogaster)



2'7'-DICHLORFLUORESCIN DIACETATE: A dye which, when oxidized produces the fluorescent 2'7'-dichlorofluorescin



DICHLOROINDOPHENOL: See Diaphorase



2,4-DICLOROPHEOXYACETIC ACID:A synthetic plant auxin and herbicide



DICKKOPF-1: Gene downstream target of β-catenin/TCF, antagonist of Wnt. Protein produces a block between DN1-DN2 in thymocyte
proliferation/maturation. Soluble Dkk-1 may be an important inhibitor of Wnt in multiple myeloma



DICTYATE (applied to ova): Resting - between meiosis I & II



DICTYOSOME: Flattened vessels (cisternae) in stacks, making up the Golgisome



DICTYOSTELIUM DISCOIDIUM: An amoeba, referred-to as a slime mould. It is a eukaryote, and passes from a single cell form to a multicellular form,
then a fruiting body.



DIDS: 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid. Anion transport blocker; monocarboxylate transporter inhibitor



DIELECTRIC: The material in an electric flux that can absorb & retain electrical energy; see Permittivity



DIETHYLMALEATE: A specific oxidant of GSH



DIFFRACTION-LIMITED: Light microscopy resolution is unable to differentiate points closer than ~250 nm



DIFFUSE INFILTRATIVE LYMPHOCYTOSIS SYNDROME: An unusual manifestation of HIV-1 infection; diffuse infiltrates of predominantly T8 lymphocytes in the parotids, lung, kidney and occasionally other organs. It is said to carry an improved prognosis, maintaining good levels of peripheral blood T4 cells and having an increased level of peripheral blood T8 cells. The process seems antigen driven. The glandular/duct components of the parotid are surrounded by lymphocytes, cause obstruction of secretions. No satisfactory treatment of the resulting disfigurement is current



DIGITONIN: Non-ionic detergent that can permeabilize cellular (plasma) and nuclear membranes, allowing the intentional insertion of chosen chemicals
into the cell (or nucleus).



DIGs: Detergent-insoluble glycolipids; caveolae act as such



DIHYDROETHIDIUM: A superoxide-sensitive fluorescent indicator



DiI: 1,1'-dioctadecyl-3,3,3',3',-tetramethylindocarbocyanine perchlorate. Used to isolate endothelial cells; fluorescent lipid analogue and vital membrane dye



DILEUCINE-BASED SIGNAL: Consensus motif (D/E)XXXL(LI); Refer to AP-2



DILS: Diffuse infiltrative lymphocytosis syndrome (See under full name)



6-DIMETHYLAMINOPURINE: A non-specific kinase inhibitor



DiNa: Differential evanescence nanometry; a method used on TIR wide field illumination to separate images



DINITROPHENOL: A decoupler of oxidative phosphorylation



DIO: Fluorescent lipid analogue



DIO-C6: Mitochondrial reporter dye; mitochondria that have lost their Δψm are unable to retain the decoration



DiOC7: 3,3-dihexyloxacarbocyanine iodide; a dye used to measure the number of perfused vessels in a section of a tissue



DipA: A pore-forming protein in the outer membrane of Lyme disease spirochaetes



DIPEPTIDYL PEPTIDASE IV: Marker of apical cell membrane surface (as for enterocytes in culture)



DIPLOTENE: First meiotic prophase; in each pair of chromosomes the units start to repel the other and split



DIPROTIN A: Stimulates mesenchymal stem cells



DIPYRIMIDOLE: 'Persantin'; PDE inhibitor. It enhances NO/cGMP/cGK signalling



DISACCHARIDE CODE - for components of Heparan and Chondroitin sulphates :

Alphabetical 1

Numerical 1

Alphabetical

Numerical 2

Non-reducing end

descriptor

Non-reducing end

O-Sulphation

Hexosamine

descriptor

Hexosamine

O-Sulphation

U = Undesignated uronic Acid

0 = No sulphation

A = Glucosamine

0 = No sulphation

D = D4,5-Unsaturated uronic Acid

2 = 2-O-sulphation

g = Galactosamine

3 = 3-O-sulphation

G=Glucuronic acid

3 = 3-O-sulphation

M = Anhydromannose

4 = 4-O-sulphation

I = Iduronic acid

6 = 6-O-sulphation

T = Anhydrotalose

6 = 6-O-sulphation

g = Galactose


Amine substitution

9 = 3,6-O-sulphation



H = Free amine

10 = 4,6-O-sulphation



A = N-acetylated




S = N-sulphated




R = amino-tagged



eg D0A0 = ΔUA - GlcNAc

D2S6 = ΔUA2S – GlcNS6S

D0a4 = ΔUA - GalNAc4S



DISC: Death-inducing signalling complex; comprising the activated, trimerized DR + cytoplasmic FADD + pro-caspase-8. This allows auto-activation of caspase-8, then caspases 3, 6 & 7. Most cells are 'type II', meaning that the intrinsic, mitochondrial pathway needs to be invoked for successful apoptosis. 'Type I' cells, such as lymphocytes, can activate apoptosis effectors without the intrinsic pathway (involving Bid).



DISHEVELLED: A modular intracellular phosphoprotein activated by FZD by phosphorylation (as by CK1 & 2, PKC & MAK) binds with the
GSK/Axin/APC. It plays an important part in the three main pathways from Frizzled activation. Transported by microtubules to the dorsal aspect of an
embryo. It has domains :

DIX: Dishevelled-Axin
PDZ: PSD95-Discs Large-ZO1
DEP: Dishevelled-EGL10-Pleckstrin



DISJUNCTION: Separation, as with centrosomes at mitosis. Nek2A mediated displacement of C-Nap1 and the activity of Eg5 appears to be necessary



DISMUTATION: Enzyme reaction involving both oxidation & reduction, or decarboxylation :

(eg SOD: O2/ + O2/  + 2H+ ⇒ H2O2 + O2)



DISOMY: Part or all of both chromosomes in a pair come from one parent



DISPASE: From Bacillus polymyxa; a proteinase. Used to digest tissues in order to release cells (eg thymus)



DISULPHIDE: R-S-S-R'



DIV: Days in vitro



DIX: see Dishevelled



DJ: Distal junction



DKC1: Dyskeratosis gene; codes dyskerin, an enzyme responsible for ~100 specific uridines into pseudouridines in ribosomal RNA



2,3-DKG: 2,3-L-diketogulonate; DHA's hydrolysis product, then yielding L-xylonate and L-lyxonate



DKK: Dickkopf proteins (lit. thick-head). DKK-1 to 4; antagonize Wnt signalling. They have 2 characteristic cysteine-rich domains. DKK-1 is involved in
head formation in the embryo. They bind competitively to LRP5/6, instead of Wnts. They may be important in bone resorption in multiple myeloma



DKO: Double knock-out (eg eliminate the effectiveness of two gene)



DL1: Delta-like1; a Notch ligand; expressed by thymic epithelium



DLBCL: Diffuse large B-cell lymphoma; believed to fall into three main classes: BCR, Oxidative phosphorylation (Ox phos) and Host response tumours (HR); some are said to have 'tonic BCL' activity, thought to be associated with a high level of Syk phosphorylation, which may sustain growth -  "BCR-type". Two immune system genes TNF & LTA appear to be involved by polymorphism in the incidence of NHL. Inhibiting Syk in those with functional BCR pathways can induce intrinsic apoptosis in many lines



DLD: D-lactate dehydrogenase (EC 1.1.1.28). Found in the inner matrix of mitochondria (access requires shuttles). Widely expressed in heart, liver,
skeletal muscle and kidney. Low levels in brain, placenta, lung and pancreas



DLG: Disc large protein



DLL-4: Delta-like ligand-4; a Notch ligand



dLN/DLN: Draining lymph node (ie a lymph node receiving lymph from the area of interest)



DLP1: Dynamin-like protein; involved in mitochondrial shaping; See Drp1



DLPC: Dilinoleoylphosphatidylcholine; 1,2-dilinoleoylphosphatidylcholine; can auto-oxidate



DLT: Dose-limiting toxicity



DLX2: A marker for neural transit-amplifying cells



DM: (a) Drosophila melanogaster; fruit fly

(b) HLA-DM (H2M, H2DM in mice)

  1. Distal myopathy

    (d) Differentiation medium



17-DMAG: An Hsp90 inhibitor; potentiates TNF-induced apoptosis of malignant cells, possibly involving suppression of IKKβ levels





DMAP: 6-dimethylaminopurine; a non-specific kinase inhibitor



DMARD: Disease modifying anti-rheumatic drug



DMAV: Dimethylarsonic acid; Cacodylic Acid



DMC: Demecolcine; inhibits microtubule polymerization



DMD: Differentially methylated domain - of genes, where methylation (imprinting) is restricted to a short region



DMA: Drug metabolizing enzymes



DMAPT: Dimethylamino-parthenolide; an analogue of PTL; appears to have an anti-leukaemic action



DMEM: (a) Dulbecco's minimal essential medium (for cell culture)

(b) Dulbecco's modification of Eagle's medium



DMO: (a) 5,5-Dimethyl-2,4-oxazolidinedione; a non-metabolizable weak acid, pKa 6.1, used in cell culture to adjust pH

(b) Directed motion



DMP1: Dentin matrix acidic phosphoprotein 1; derived from osteocytes & osteoblasts and cleaved into two phosphoproteins by BMP1 - C-terminal is
a mineralization nucleator for extracellular matrix; absence stimulates FGF23 production (see FGF23, PHEX)



DMPS: 2,3-Dimercapto-1-propane sulphonate; a water soluble chelating agent that can be administered by mouth to treat metal intoxication



DMR: Differentially methylated region (of gene)



DMS: N',N'-Dimethylsphingosine; inhibits SphK1 by dative damage to carbonylation



DMT: N,N-dimethyl tryptamine; an endogenous agonist for Sigma-1R



DMZ: Dorsal marginal zone



DN: Double negative - CD4- CD8- cells, (also lacking TCR) found early in the thymic maturation series - further subdivided (DN1-4) by the surface receptors CD44 & CD25. A pre-TCR appears on DN3 cells, allowing proliferation and differentiation, and conversion to double positive thymocytes. DN2 & 3 are the most actively proliferating types, possibly driven by IL-7; by DN4, there is loss of responsiveness to IL-7, and other factors are probably involved.



dn: Dominant negative (eg dnTGFβR), effectively removing the receptor etc.



DNA: Deoxynucleic acid. The building blocks of genes and chromosomes, forming pairs of chains in a spiral configuration



DnaA PROTEIN: Initiator of chromosomal replication; function is affected by membrane lipids



DnaK: An E. coli Hsp70 chaperone



DNA LIGASE III: Involved in single and double strand DNA repair



DNA METHYLATION: It is involved in genomic imprinting, occurring at the 5-position of cytosine residues, usually in CpG islands, and is catalysed by DNA methyltransferases. It probably distinguishes the genes if one parent from the other, is epigenetic, heritable and an inhibitor of transcription. Germ-line genes can switch methylation in keeping with the parent's sex. It stabilizes the DNA but, in the case of cancer, when there is excessive methylation to down-regulate key gene expression there is a paradoxical hypo-methylation globally. Key genes that may be methylated include those for cadherin, heparan sulphate, tissue inhibitors of proteinases, axon guidance, thrombospondins and laminins etc. In some, it is the loss of methylation that seems to make possible metastasis.



DNA-PK: DNA-dependent protein kinase; a Serine/Threonine kinase, with a 460 kDa catalytic subunit (DNA-PKcs) and a DNA-binding heterodimer of 70
and 86 kDa subunits. DNA-PKcs is involved with double-strand break repair; may be attracted to the DNA ends by Ku70/80



DNA REPLITASE: A presumed complex of enzymes associated with DNA repair prior to the S phase. It includes UDG



Dnase: Families of endonucleases that can cleave DNA chains

Dnaseγ: Endonuclease that can contribute to ATP-independent DNA fragmentation during necroptosis



DNAzymes: DNA-based enzymes



DNB-Cl: &-Chloro-4-nitrosobenzeno-2-oxa-1,3-diazol. Forms adducts with reduced thiols and sulphenic acid, which show identifying spectra



dNFAT: The Drosophila NFAT equivalent, more like the human NFAT5 (not Calcium dependent)



DNFB: 1-Fluoro-2,4-dinitrobenzene; produces a delayed-type of skin sensitivity.



DNMT1-10(?): DNA methyltransferase; a family of factors involved in methylation of DNA

DNMT2 = tRNA aspartic acid methyltransferase 1



DNP: (a) Dinitrophenol

(b) DNA nanoparticles; non-viral gene transfer vectors; nucleolin and lipid rafts are needed, also microtubules



DNQX: 6,7-dinitroquinoxaline-2,3-dione; inhibitor for non-NMDA receptors



Doa4: (Degradation of α2.) Enzyme that de-ubiquinates MVB cargoes at the endosomes and is recruited to the ESCRT-III



DOCK 180: Involved in mammalian engulfment of apoptotic cells



DOK-1: Docking protein 1, an inhibitory adaptor protein that suppresses the MAPK downstream pathway



DOC-3: An adapter protein



DOCETAXEL: A lipophilic, Taxane chemotherapeutic agent; enters cell well and persists there; affects microtubular assembly/disassembly, producing
microtubular bunching/bundling, also inhibits Bcl-2, encouraging apoptosis; can have serious side effects



DOI: (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane. An hallucinogen with high affinity for 5-HT2A & 2C receptors, which can be coupled to
PLA2



DOLUTEGRAVIR: An human immunodeficiency virus type-1 integrase inhibitor



DONEPEZIL: A cholinesterase inhibitor in use for treatment of Alzheimer's Disease; has affinity for Sig-1R



DOPC: Dioleoylphosphatidal choline



DOR: Delta opioid receptor



DORFIN: E3 ubiquitin ligase



DOT (or Slot) HYBRIDIZATION: Technique of placing crude denatured cellular constituents on medium, overlaying 32P-labeled cDNA plasmid preparation and then autoradiograph. By this means, large numbers of specimens can be processed together



DOUBLECORTIN (DCX): Neuronal microtubule-associated protein (MAP), associated with X-linked lissencephaly (smooth brain)



DOUNCE: To homogenize by forcing & rotating a plunger down a tube containing the material to be dispersed; there being a slight gap between the plunger width & the tube diameter



DOWNREGULATION (with respect to Golgi/endosomes): Term indicating that contents/molecules are destined to destruction (via ubiquination/proteasomal)



DOWN, John Langdon Haydon: English physician, the eponym for the syndrome



DOWN'S SYNDROME: Congenital abnormality, with dysmorphic skeletal, retarded brain development and other features, usually associated with trisomy of chromosome 21. Those with it tend to have a higher incidence of certain diseases, such as chronic myeloid leukaemia. There is a claim that, in a mouse model for Down's syndrome, a serotonin re-uptake inhibitor (fluoxetine) may allow more normal brain development



dp: Degree of polymerization



DP: (a) Double positive, as of thymocytes (eg CD4+ CD8+). These are very sensitive to glucocorticoids in vivo, causing cell death/apoptosis

(b) Desmoplakin



DPC: (a) Distal pole complex; an actin remodelling on the opposite side of a T cell to its immune synapse

(b) Day post coitus



DPI: Diphenyleneiodonium chloride; A catalase/NOS/NOX inhibitor



DP-NPT: Desmoplakin's N-terminal polypeptide containing the first 584 residues



DPP: Decepantaplegic; a member of the TGF-α superfamily. See Dally



Dpp-IV: Dipeptidyl peptidase-IV; an apical cell surface marker, as for identifying the luminal surface of enterocytes



DPPH: 2,2-diphenyl-1-picrylhydrazyl; a free radical scavenger



DPQ: A PART-1 specific inhibitor



DR: Death receptor, of the TNF family; receptors that, when stimulated by appropriate ligands, trigger the 'extrinsic' apoptosis pathway through an intracytoplasmic death domain

DR1: TNFR1

DR2: Fas

DR3: TRAMP

DR4: TRAIL-R1; has fucosylated glycan(s); [not used in mice]

DR5: TRAIL-R2, Apo-2, TRICK2, KILLER; has 2 isoforms; does not have fucosylated glycan(s)

mDR5: mTRAIL-mKILLER in mice

DR6

EDAR

The death receptors can also participate in non-cytotoxic signalling pathways, such as cell proliferation, differentiation, chemokine production and inflammatory responses, by activating NF-κB, MAPK, PI3K & JNK. GMDS does not affect the non-cytotoxic functions of TRAIL



D1R: Dopamine-1 receptor



DRAK2: Death-associated protein kinase-related apoptosis-inducing kinase



DRB: 5,6-Dichlorobenzimidazole 1-β-D- ribofuranoside; a transcription elongation inhibitor



DRC-1: Marker for follicular dendritic cells



DRD1: Defective in RNA-directed DNA methylation 1, an SNF2-like chromatin remodelling protein



DRF: Detergent-resistant membrane fraction



DRG: Dorsal root ganglion



DRIP: Vitamin D Receptor (VDR) interacting protein



DRM: (a) Detergent-resistant membrane

(b) Down-regulated by v-mos = Gremlin (see Gremlin)



DRM2: Domain rearranged methyltransferase; a DNA methyltransferase



DROSHA: An endonuclease that excises the miRNA stem loops from the primary transcript (pri-miRNA); A mRNA regulating enzyme (ef Dicer); colorectal cancer may express increased amounts



DRP1: Dynamin-like protein; associated with mitochondrial fission; downregulation delays the activation of caspases & onset of apoptosis



dRVVP: Dilute Russell viper venom time; coagulation test



DSB: Double strand break of DNA. More serious than a single strand break Can be induced by ionizing radiation or Laser micro-irradiation. The following factors can be involved with DSBs, but are not restrained at the site, activated elsewhere or diffusing away: DNA-PK, Ku70, Smc1, Smc3, Chk1, Chk2, p53 and Cdc25A



DSC3: Gene for DSC3; often subject to epigenetic down-regulation in malignancies such as breast cancer



DSC: (a) Disaccharide structural code; a new code to present the disaccharide basic units and how they combine (a four digit descriptor)

(b) Desmocollin; component of desmosomes



DSCR1: Down's syndrome critical region; see RCAN1



dsDNA: Double-stranded DNA



DSG: (a) Deoxyspergualin, an immunosuppressant. It has been trialled in humans for various immune-related diseases, but it is unstable (to a polyamine oxidase in foetal calf serum) and toxic. See LF 08-0299, LF 15-0195

(b) Desmoglein; (component of desmosomes)



Dsh: Dishevelled; it has four domains:

DEP - required for β-catenin signalling

PDZ - required for PCP & β-catenin signalling

DIX - required for PCP signalling & relocation of Fz



dsRBD: ds-RNA-binding domain



DSL: Delta-Serrate-Lag2 domain; cysteine-rich, a feature of all notch ligands



D-SPACE: The membrane bilayer width plus surface hydration; may be in the order of 48 Å, rising slightly to ~51 Å with added cholesterol, then dropping after lipid peroxidation to ~34 Å



dsRBD: dsRNA-binding domain



dsRBP: Double stranded RNA-binding protein; such proteins bridge RNAs to form RNP complexes; for this, there are binding domains (dsRBDs)



dsRNA: Double-stranded RNA; such fragments can be cleaved by a Dicer-like RNase (DCL-4) to produce 21 nt tasiRNA



DSS: (a) Dextran sodium sulphate; 40 kDa, 4% added to drinking water induces colitis in mice; a mixture with AOM induces inflammation-associated cancer; a process that may involve NLRP3 => IL-18 in mice

(b) Disuccinimidyl suberate



DT40: Avian B-cells; pre-lymphocyte; well studied



DTC: Distal tip cell



DTG: Di-O-tolylguanidine; a sigma-1R ligand



DTH: Delayed-type hypersensitivity



DTPA: Diethylenetriaminepentaacetic acid; a chelater (eg for Fe)



DTT: Dithiotreitol; a reducing agent widely used in biology as an antioxidant or to reduce oxidized groups, (eg GS−SG)



DU-145: Human prostate cancer cell line; androgen-responsive, with the androgen receptor is confined to the nucleus



DUB: De-ubiquitinating enzyme



DUCHENNE, Guillaume Benjamin Amand; French Neurologist (1806-75)



DUDENG: Mu-2-related death-inducing gene; encodes a ~54 kDa protein in humans; probably involved in trafficking proteins from endosomes towards other membranes & also in cell death



DUF: Domain of unknown function



DUO: See HAPIP



DVL: See Dishevelled



DYING-BACK OLIGODENDROGLIALOPATHY: Degenerative changes that involve the processes of the oligodendroglial cytoplasm; showing multiple vesicles, accumulation of mitochondria and deposits of granular or crystalline material. Some form of MS show this, as do toxic and mutant forms



DYNACTIN: Centrosomal dynactin is required for normal microtubule anchoring &/or focusing independently of dynein



DYNAMIN: A GTPase, involved in the pinching-off (fission) of membrane pits to form vesicles. Conventional synapses have Clathrin-dependant inward budding involving dynamin, blocked by GTPase inhibitors. Involved in Golgi budding, uses GTP and is required for membrane budding at a late stage during the transition from a fully formed pit to a pinched-off vesicle. Dynamin acts at two steps during clathrin coat formation: U-shaped, half formed pits and O-shaped, fully formed pits, captured while pinching off; GTP hydrolysis is probably needed at both steps



DYNAMITIN: A subunit of dynactin, that sequesters other dynactin components and leads to dynactin disassembly when in excess.



DYNASORE: A cell permeable molecule that interferes in vitro with the GTPase activity of dynamin1, dynamin2, and Drp1, the mitochondrial dynamin, but not of other small GTPases



DYNEIN: A motor protein. Associated with ATP, with 6 ATPase domains. MW~1.9 MDa for the outer dynein arm of the axoneme. Has two tubulin binding sites, each arising from a large globular C-terminal group, attached to smaller, globular cargo-binding N-terminal end. Has 13 different polypeptide components. The inner dynein arm of flagella/cilia has 3 main components and nexin links forming a complex. Has a light chain ~8 KDa which seems important in apoptosis pathways. Generally moves towards the centrosome. Outer arms seem to affect beat frequency - some species can lack the outer arm (eg European eel; Anguilla anguilla).

The so-called dynein-dynactin complex binds to vesicles through the interface between Arp1 and spectrin (fodrin)



DYNLL1: Dynein light chain 1; see LC8; its pro-apoptotic target is Bim



Dyrk1a: Duals specificity tyrosine phosphorylation regulated kinase A kinase that phosphorylates NFATc and drives it back to the nucleus. (As do PKA and GSK)



DYSTROGLYCAN: A non-integrin laminin receptor associated with dystrophin in the DGC



DYSTROPHIN: Has lateral associations with actin filaments in myofibrils; part of the DGC



DYT1: A dystonia that is a genetically-determined form of early onset. There is a trinucleotide deletion of a ΔGAG codon in the DYT1 (TOR1A) gene, with a loss of glutamic acid from the torsinA protein



DzA: Egr-1 DNAzyme



DzF: Egr-1 DNAzyme



E (proteins): See bHLH proteins



E1 - 3: Terms for enzymes -1 to -3 that attach ubiquitin to soluble proteins to be targeted to the regulatory unit of the proteasomes, to be degraded by the catalytic units of the proteasomes (E1, Ub-activating; E2, Ub-conjugating; E3, a Ub protein ligase to transfer Ub to specific substrates). Transmembrane proteins are covalently bound by a single ubiquitin unit. These complexes are then recognized and transferred to lysosomes (which have surrounding membranes). This often involving incorporation of the receptor into budding vesicles into the lumens of the endosomes (forming multivesicular bodies), which then merge with lysosomes



27E10: Early inflammatory activity marker



EAAT4: Neuronal glutamate transporter



EAC: Ehrlich ascites carcinoma; may be derived from mouse mammary cancer



EACA: Epsilon-aminocaproic acid; a C-terminal lysine mimic; a Lysine analogue that interacts with LBS with great affinity; EACA: (= ε-aminocaproic acid);



EAE: Experimental allergic/autoimmune encephalomyelitis; a condition induced in experimental animals by injecting various extracts of brain; considered to be an experimental model for Human Multiple Sclerosis, although there are points of difference



E64/E64c: N-(trans-Epoxysuccinyl)-L-Leucine 4-guanidinobutylamide; an active site inhibitor for (lysosomal) cysteine proteases (eg calpain/cysteine)



EB: (a) Epidermolysis Bullosa. An hereditary skin condition characterized by skin blisters following minimal/mild trauma as a result of a mutation of ColVIIA1, and the failure to form anchoring fibrils at the dermo-epidermal junction . The most severe form is recessive dystrophic epidermolysis bullosa (RDEB) which has, in addition to the skin fragility, exuberant repair reactions that can embed digits, resulting in the hands being like paddles, and the appearance of aggressive skin cancers at an early age. There may be a constitutive excess production of HB-EGF-like cytokine

(b) Embryoid body



EBP: (a) Enhancer-binding protein

(b) Emapomil binding protein



4EBP1: The binding protein of eIF4E



ECaC: See TRPV5



E2F: E2 factor; major transcription regulators of S-phase genes



EAE: Experimental Allergic Encephalomyelitis. An animal-model disease with similarities to Multiple Sclerosis in humans. The condition is induced by injecting brain extracts and adjuvant into laboratory animals, the symptoms appearing after about 10 d. It is generally considered to be primarily a CD4+ T cell medicated disease, and sensitized CD4+ can induced it in a recipient, but B cells and humoural antibodies seem important at the induction stage. When sensitized lymphocytes are transferred, symptoms start in ~5 d, waning 11-12 d; then there is a relapse ~28-40 d. IL-1β appears to be important and promotes an encephalogenic Th17 response, indicating that inflammasomes are involved (however IL-1 may be involved in later remyelinating & remodelling)



eag: (ether-a-go-go) gene for a family of K+ channel proteins



EAG: A K+ channel protein with receptor-like activities, similar to ERG, which may influence cell cycle activity and be involved in oscillations and oncogenesis



EAM: Experimental autoimmune myocarditis



EAMG: Experimental autoimmune myasthenia gravis; can be induced by transfer of anti-AChR antibodies into mice, or active immunization, the latter producing a T-cell response



EAP: ELL-associated protein (human orthologues of ESCRT-II subunits), the numerals of the EAPs refer to kDa:

EAP45/Vps36

EAP30/Vps22

EAP20/Vps25

The (ELL + the above 3 EAPs) constitute a 'holo-ELL complex' augmenting the catalytic activity of transcription elongation of RNA polymerase II



EB: Embryoid body; form during the in vitro differentiation of embryonal stem cells, into mesoderm, ectoderm and endoderm



EB1, -2, -3: End-binding-1, -2 (RP-1), -3; microtubule-binding protein(s) at the plus end; possibly involved, with APC in attachment to the plasma membrane

EBAG9: ER-binding fragment-associated antigen 9; one of the genes targeted by oestrogen receptors



EBP: Emopamil binding protein



EBP50: ERM (ezrin, radixin, moesin)-binding phosphoprotein 50



EBSELEN: A glutathione peroxidase mimetic



EC: (a) Epithelial cell

(b) Enterocyte

(c) Embryonal carcinoma (cell); the undifferentiated cells of teratocarcinoma from ascites in vivo 



E-C: Excitation-contraction; relating to a small Ca2+ stimulus resulting in contraction 



ECACC: European Collection of Cell Cultures



E-CADHERIN: Mediates lateral membrane interactions; has long extracellular & cytosolic extensions, the extracellular ones form homophilic links with those of adjoining cells, and link with actin/myosin etc. via β-catenin; a feature of epithelial cells; binds with ankyrin, α-catenin & β-catenin :

for ankyrin on E-cadherin is : KEPLLPPEDDTRDNVYYYDEEGGGEED

for ankyrin on N-cadherin is : KQLLIDPEDDVRDNILKYDEEGGGEED (differences underlined)

The trio of ankyrin-G, E-cadherin and β-2 spectrin are necessary for dispatch (via microtubules) from the Golgi, the formation of lateral cell membranes and cellular compaction in embryo development. Refer for gene CDH1 & associated



ECD: (a) Evolutionarily conserved domain

(b) E-cadherin



ECF: Extracellular fluid



ECFP: Enhanced cyan fluorescent protein (ECFP) fusion protein; marker for ER



E-CFU: Endogenous CFU, see CFU



ECHINODERM: member of Echinodermata - phylum includes starfishes, sea urchins etc



ECL: Extracellular loop (eg ECL2 = second extracellular loop)



ECM: Extracellular matrix



ECMR III: See CD44

ECOG: Eastern Cooperative Oncology Group



ECOG PERFORMANCE STATUS: A scale of well-being applicable to oncology patients (see also Karnovsky)

    1. Fully active, able to carry on with all pre-disease performance without restriction

    2. Restricted in physically strenuous activity, but ambulatory and able to carry out work of a light or sedentary nature (eg light house work or office work)

    3. Ambulatory and capable of self-care, but unable to carry out any work activities. Up and about more than 50% of waking hours

    4. Capable of only limited self-care, confined to bed or chair for more than 50% of waking hours

    5. Completely disabled. Cannot carry-on any self-care. Totally confined to bed or chair

    6. Dead



ECRF3: CXC chemokine receptor, 321 aa, induced by Herpesvirus saimiri



ECT: (a) Electroconvulsive therapy; the initiation of epilepsy-like convulsions by applying electrical currents to the head

(b) Electrochemotherapy; the application of short duration electrical pulses to tumours to make the plasma membranes transiently permeable. Drugs that are poorly permeable into cells may be aided into the cells by this means (eg bleomycin may be some 300-700 more cytotoxic)



ECV: Endosomal carrier vesicles = MVB



ECV304: Human aortic endothelial cell culture line



ED: Embryonic day



E64d: L-transepoxysuccinyl(OEt)-Leu-3-methylbutylamide; a cysteine cathepsin inhibitor



ED5: (a) An FDC-associated antigen

(b) A DNAzyme that cleaves mouse Egr-1 RNA in a time a sequence-specific manner



EDA1: Ectodysplasin A; has a proteolytic processing site, a collagen domain and a trimeric TNF homology domain; involved in skin appendage formation



EDAA: Endocytosis adaptor complex



EDAR: Ectodysplasin A receptor



EDN1: Endothelin 1



EDO-P4: Blocks glucosylceramide formation



EDSS: Expanded disability status scale.



EDTA: Ethylenediaminetetraacetic acid: as tetrasodium salt:

(NaOOC-CH2)2N-CH2-CH2-N(CH2-COONa)2

A chelator of divalent cations, such as Calcium and Magnesium, also heavy metals. When added to culture media for mouse embryos, it reduces intracellular Magnesium from ~310 mM to ~200-5 mM. This is believed to suppress glucolysis at 10 mM by removing the Magnesium from 3-Phosphoglycerate kinase. At 100 mM, the TCA is also inhibited, which reduces development of blastocysts



EEA1: Early endosome antigen-1; Chromosome 12q22; a marker for endosomes



Eeflel: Gene (mouse) for Eukaryotic translation elongation factor 1, epsilon 1



EEM: External elastic membrane (as of an artery)



EEQD: N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline; used to couple chondroitin sulphate to Sepharose beads



EF: Electrophoresis



EF1: An active peptide from the laminin α1 chain (see AG73). EF1 promotes cellular attachment via α2β1 integrin. AG73 & EF1 act synergistically in accelerating cellular adhesion



EF-2 Elongation factor 2; 96 kDa



EF31: A Curcumin analogue



EF-1A (or EF-1α): Elongation factor 1A; 49 kDa. A GTP-binding protein that is involved in DNA  transcription and associates with centrosomes. It is an abundant cytoplasmic protein that mediates the docking of aminoacyl tRNAs onto ribosomes and associates with the tubulins +/- actin at prophase/metaphase and may regulate mitosis events



EFALIZUMAB: Anti LFA-1 antibody - blocks the immune synapse; useful for psoriasis



E-field: Electric field



EFFEROCYTOSIS: The phagocytosis of apoptotic cells; HMGB1 inhibits the phagocytosis by macrophages



EF-HAND PROTEIN: A term referring to Calcium-binding proteins which have 6 potential binding sites A-F. The shape of the binding sites (E&F) is represented as being like a relaxed hand (palm up) as observed in parvalbumin, with an helix-loop-helix. See Centrin and Calmodulin.

Calmodulin

Centrin

Myosin regulatory light chain

Recoverin

Visinin

Calcineurin B

p22

In evolution, Calmodulin, Centrin, Calcineurin & p22 seem to have branched off at about the same time



EFR: A Drosophila protein that is an homologue of GFT; its substrate is not highly specific



EFS: Event free survival



EFT: Ewing's 'sarcoma' family of tumours. comprising :

Ewing's 'sarcoma'

Askin tumour (of thoracic wall)

Extra-skeletal Ewing's tumour

Neuroectodermal tumour of bone

They have a common chromosomal abnormality, t(11;22)(q24;q12) with a fusion gene



Eg5: A member of the bimC kinesin-related motor protein family; a minus-end directed motor. Recruited by Cyclin B, it participates in centrosomal separation and bipolar spindle assembly. Is inhibited by monastrol. Eg5 contains a KEN-box which makes it a potential substrate for APCCdh1. For centrosome separation, Eg5 microtubule bundling activity seems more important than motor activity



9EG7: A monoclonal antibody that can reveal an epitope of integrin β1 variable by conformational changes



EGCg: Epigallocatechin gallate; a green tea polyphenol derivative that inhibits MMP-2 gelatinolytic action; said to inhibit CD44+, Integrin α2β1hi, CD133+ prostate cancer stem cells



EGF: Epidermal growth factor. A cytokine with only a slight structural difference from TGFα. HB-EGF has a longer Heparin-binding tail; EGF activates the nuclear localization of phosphorylated Med1, associated with ERK activity



EGFP: Enhanced green fluorescent protein. Genetically inserted into molecules, which can then be tracked in vivo.



eGFR: Estimated glomerular filtration rate; obtained from a calculation using the serum creatinine level and the patient/s age (there are other variations, using parameters such as height & weight); the result is an approximate guideline of kidney function, dependent upon the accuracy & reliability of the serum creatinine; in patients aged ≥ 70 years old, a stable eGFR of 45-59 mL/min/1.73 m2, if not associated with any features of renal disease, such be considered acceptable; the upper limit for reporting has been set at >90 mL/min/1.73 m2; a recommended reporting protocol from Australasian laboratories



EGFR: (=ERBB1) Epidermal growth factor receptor - a Tyrosine kinase, which can phosphorylate many of the enzymes of the glycolytic pathway (including GAPDH 1:1), 1186 aa + N-linked oligosaccharides; produced by retroviruses. It binds heparin and can auto-phosphorylate at low temperatures.

Ligands :

EGF

TGFα

Amphiregulin

HB-EGF-like

Betacellulin

Epiregulin

Under osmotic and oxidative stress, metalloprotease activity is promoted, leading to a cell surface cleavage of a pro-HB-EGF, with EGFR activation through MAPK p38. There can be linkage between the EGFR and Wnt, with activity passing directly or indirectly from one to the other pathways, and there may also be links between a variety of cell-surface receptors, such as G-protein coupled receptors and integrins. The TGFα-EGFR activity is particularly important in colon cancer, with metastatic cells producing ~x5 that of non-metastatic cells



EGFRvIII (EGFR type III, de2-7, ΔEGFR): In ~40% of GBMs there gene amplification or over-expression, in which ~50% have a mutated form of the EGF gene, producing a receptor that is constitutively active, being unable to bind a ligand. The wild-type EGFR and the EGFvIII with HB-EGF (+TGFα augmenting) both ligands for EGFR, can form an autocrine stimulation loop



Egr1: A regulatory gene active in mature B cells; target gene of ERK/Elk4. It may be inactive in precursors because of methylation. When active, it may determine that a B cell will respond positively to antigenic stimulus; can be used as a marker for FGF23



EGR1: (=Knox24, Zif268 or NGFI-A.) A serum-inducible, zinc finger transcription factor; involved in wide-ranging systems, including inducing HPSE in activated (PMA, Calcium ionophore) CD4 T cells, smooth muscle cells and endothelial cells. Its activity can stimulate some tumours, inhibit others (eg melanoma). It binds to two sites on the HPSE promoter. A promoter binding site for Egr-1 is essential for stretch-induced induction of CCN1 in VSMCs



EGTA: Ethylene glycol-bis(2-aminoethylether)-N,N,N',N'-tetraacetic acid:

(HO-CO-CH2)2N-CH2-CH2-O-CH2-CH2-O-CH2-CH2-N(CH2-CO-OH)2

A chelator of divalent cations, such as calcium and magnesium. It does not enhance embryo culture as EDTA does, and when omitted from the preparation buffer for centrosomes, the PCM falls off the centrioles (totally ?) - microtubules then grow axoneme-like. May inhibit formation of UV-induced cation current channels in the plasma membrane



EH: Eps15 homology



EHF: Ebola haemorrhagic fever



EHRB: (Ramos subline) Burkitt's lymphoma, EBV+



EHRLICH-LETTRÉ ASCITES TUMOUR: A mouse mammary cancer cell line that grows intra-peritoneal, producing ascites.



EHS: Engelbreth-Holm-Swarm tumour (See names tumour)



eIF: Eukaryotic initiation factor: 12 described.

eIF2A: EIF2S3; Involved in the initiation of DNA transcription; eIF2α is part of the ternary complex required to chaperone the initiator tRNA to the ribosome; is commonly expressed in cancers

EIF2AK1: Involved in the PERK pathway

EIF2AK3: See PERK

EIF2AK4: Involved in the PERK pathway

EIF2S3: See eIF2α(A)

eIF4A: Involved with STRAP in the coordination of Collagen Type 1 polypeptide chain formation from translation of their mRNAs

eIF2B: Has 5 sub-units α - ε; catalyses the exchange of GDP bound to a second translation initiation factor eIF2, for GTP. eIF2B(ε) (MW 88 kDa) may modulate the stability and translation of COX-2 mRNA - may be reduced by chronic Li; it can be phosphorylated by GSK

eIF4E: Regulates the cap-dependent mRNAs; requires phosphorylation on Ser209 for initiation of translation; may be downstream of a p38-MMK1-eIF4E pathway in neutrophils that is regulated by GSK3. Binds to 4EBP1; S6K1/2 & 4EBPs negatively regulate; over-expression promotes cancer and co-operates with c-Myc in transgenic mice to drive lymphomagenesis; enhances the translation of select mRNAs (mechanism yet to be defined), possibly by the 5'UTRs

eIF6: Promotes cellular transformation; regulates the joining of a 60S ribosomal subunit to the 48S pre-initiation complex to initiate translation; interacts with RACK1



EIGENVALUE: The relaxation time to a new equilibrium (following a disturbance, eg sudden temperature rise), as a function of the rate constant of the kinetic model.



EIPA: 5-(N-ethyl-N-isopropyl)-amiloride HCl; selective blocker of Na+/H+ antiport.



E-κB: DNA sequence that up-regulates the transcription of TNF and IL-6; the target for NF-κB



ELAM-1: Endothelial leukocyte adhesion molecule-1; see E-selectin



ELASTASE (Neutrophilic): Destroys SDF-1 in the blood stream; see also Neutrophil elastase



ELC: Epstein-Barr virus-induced molecule 1 ligand chemokine (CCL19)



ELECTROPORATION: The application of a strong electromagnetic field (eg 1.5 kV; 10 kHz for 300 ms) across an oocyte/other held in a medium with the ion to be introduced; the plasma membrane develops pores on the + voltage side When the pulses are <100 ns, the nature of the effects upon cells change, with global plasma membrane damage (nanopores ?) with phosphatidylserine externalization and damage to organelles. The estimated transmembrane voltage required to achieve this is ~0.5 V



ELEM: Extremely low frequency electromagnetic (field; see ELF-EMF). The dielectric constant of water treated with 1-10 GHz has been reported to be 3.7% higher than the control



ELF1: A dwarf splice variant of Spectrin β II



ELF-EMF: Extremely low frequency electromagnetic field; reported to produce relatively long-lasting changes to glutamic acid solutions, without spectral features, indicating electron shift and hydrogen bonding changes. Such observations may augment reported changes reported for living cells



ELKS: Glutamate (E), leucine (L), lysine (K) and serine (S). Found at CAZ of synapses. See RET. Interacts with Rab6 and is regulatory subunit of IκB kinase complex in the NF-κB signalling cascade. ELKS1=ERC1/CAST2, with two C-terminus alternative splices, ELKS1A & B. ELKS2=CAST/ERC2. ELKS 1A & 2 are 120 kDa with a C-terminal-consensus-binding motif for binding to PDZ found in RIM1α, RIM2α/β and syntenin-1. Through CC regions ELKS binds to multi-domain proteins liprin-α and to Piccolo/aczonin and Bassoon. ELKS are necessary to locate RIM to the active zone. Impairment of ELKS to RIM & Bassoon binding impairs synaptic transmission



ELKS: Genes (large) x2, ELKS1 & 2



ELL: An RNA polymerase II elongation factor



ELONGATION FACTOR: See EF-1A



ELP: Echinoderm microtubule-associated like-protein. See EMAP



EM: Erythema migrans; a round, red expanding rash that develops a pale centre (“bull's eye”); Lyme disease cases may have such a rash (~50%) associated with the infected tick 's puncture site



EMAP: (a) Echinoderm microtubule-associated protein. Have a highly conserved hydrophobic ELP (HELP) domain and large tryptophan/aspartic acid repeat domain. 70 kDa human version binds to MTs stoichiometrically 0.4/1 of tubulin dimer. Reduces growth rate & MT catastrophes - shorter MTs

(b) Endothelial-monocyte activating peptide



EMBDEN, Gustav Georg: A leading German biochemist involved in the elucidation of the glycolytic pathway



EMBDEN-MYERHOF-PARNAS: The 'classical' glycolytic pathway, comprising 10 enzymes in a cascade :

Name

Abbreviation

EC Code

Hexokinase

HK

EC 2.7.1.1

Phosphoglucose isomerase

PGI

EC 5.3.1.9

Phosphofructose kinase

PFK

EC 2.7.1.11

Fructose-bisphosphate aldolase

FBA

EC 4.1.2.13

Triosephosphate isomerase

TPI

EC 5.3.1.1

Glyceraldehyde-3-phosphate dehydrogenase

GAPDH

EC 1.2.1.12

Phosphoglycerate kinase

PGK

EC 2.7.2.3

Phosphoglycerate mutase

PGAM

EC 5.4.2.1

Enolase

ENO

EC 4.2.1.11

Pyruvate kinase

PK

EC 2.7.1.40



See Glucolysis and Glycolysis.



EMBIGIN: Membrane glycoprotein; See GP-70



EMBRYO STAGES: Mouse (very approximate): -

Stage

Hour

Day

Ovulation

0


Fertilization

12


Zygote

12 — 36

1

2-cell

36 — 60

2

4-cell



8-cell

60 — 84

3

Early blastocyst

84 — 108

4

Blastocyst

108 →

5 →



EMBRYONAL STEM CELL: See human embryonal stem cell



EMBRYO TRANSFER: The transfer of in vitro embryos back into the genital tract environment for further development - considered the definitive assessment for embryo viability



EMETINE: Induces apoptosis and protein biosynthesis



EMG Syndrome: (=Beckwith-Wiedemann Syndrome) Exophthalmos-macroglossia-gigantism syndrome; see Beckwith-Wiedemann Syndrome



EMI DOMAIN: A small module rich in cysteines and found in EMILINs and multimerin



EMILIN: Glycoproteins of the extracellular matrix characterized by a C-terminal C1Q domain

EMILIN-2 may induce apoptosis by activation of the death receptor DR-4



EMMPRIN: Inducers of matrix metalloproteinase secretion: in apical membrane of RPE. See Basigin, CE9, neurothelin, M6, CD147 or OX-47 (in rat). Transmembrane domain is highly conserved and contains a negatively charged glutamic acid residue, which probably reacts with other membrane proteins



EMOPAMIL BINDING PROTEIN: Mutations of the gene cause Conradi-Hünermann-Happle syndrome



EMP: Embden-Meyerhof-Parnas. The main glycolytic pathway, prominent in anaerobic glycolysis, named after leading biochemists involved in its elaboration.



EMPERIPOLESIS (Emperiopolisis ?): Lymphocytic penetration of and movement within another cell



EMSA: Electrophoretic mobility shift assay



EMT: Epithelial-mesenchymal transition; in embryology, epithelial cells acquire fibroblast-like characteristics, with reduced intercellular adhesion (E-cadherin reduction), increased cell-to-ECM interactions and increased motility. In the presence of a basement membrane, the actin cytoskeleton accumulates in the apico-lateral part of the polarized cell. Without the basement membrane, actin disperses and the cell loses polarity. The loss of E-cadherin recovers when the cell types stabilize. Progeny of irradiated human breast cancer cells in vitro undergo EMT when stimulated by TGF-β. During EMT laminin-332 is down-regulated, assisting cell invasion. Laminin is degraded by MT1-MMP or MMP2 providing fragments which may stimulate migration, and vimentin is up-regulated as are proteases, such as MMPs. Important signalling pathways for EMT induction include: Wnt, TGF-β, Hedgehog, Notch and NF-κB, affected by external stimuli collagen, fibronectin, EGF and HGF; regulation by transcription factors, slug, snail, twist & zeb1. With metastasis, the factors directing EMT may be diminished, and the process may reverse (MET). Cancer tissues may prevent the assembly of basal membrane components

Some factors that may induce EMT

Markers/features induced

TGF-β

Loss of cell adhesion

Wnt

Loss E-cadherin

TNF-α

Gain of N-cadherin

Snail

Gain of CD44 (via Activin A)

Slug

Gain of vimentin


Gain of S100A4


Gain of αSMA

ENaC: Epithelial Na+ channel; said to be involved in cell migration & wound healing; the α subunit associates with spectrin and short actin filaments and binding with these affects the channel; see DEG/ENaC



EndoG: Endonuclease G; apoptosis inducing factors; mediate chromatin condensation and DNA fragmentation; move from the inter-membrane space of mitochondria into the nucleus where they mediate chromatin condensation and DNA fragmentation



ENDOGLIN: CD105; receptor for TGF-β1. It is a marker for neo-vascularization endothelial cells. Intra-tumoural levels are considered to relate to metastasis and poor prognosis. Soluble endoglin can be detected in the blood and also matches metastasis and poor prognosis measures.



ENDOPHILIN A: Involved in Clathrin-dependant vesicle endocytosis. Dynamin is coupled to endophilin A in vesicle formation by the clathrin-coat complex. Combines with VGLUT1 after high frequency stimulation



ENDOPLASMIC RETICULUM: Fine channels that course through the cytoplasm, apparently leading to the Golgi and are continuous with the nuclear envelope; comprise ~50% of total membrane of liver cells & ~20% volume of pancreatic β cells. They are thought to interconnect. Ribosomes are attached to the external walls and produce nascent peptides, which are maintained and shaped by chaperonins with glutathione and an energy source Ero1; redox potential at points of protein oxidation is -180 mV; accordingly, ~99% of HMGB1 should be oxidized at secretion (which is non-classical, but by secretory lysosomes). Provides a significant store of bound Calcium, with most of the ER Ca2+ sensitive to InsP3 (a brief surge over ~7 min) or histamine (for release of Ca2+), however, there appears to be heterogeneity in Ca2+ binding within the system. How concentrated the Ca2+ is, depends upon a number of factors, with values given ~700 mM, ~2-3 mM, 1-5 mM, 200-1,500 μM, with ER ~1-3% of cytosol (SR ~1.5-7.5 mM). The free Ca2+ in the ER ~20% of total there ~5 mM. (See Calcium) ER stress > 4 h may induce apoptosis



ENDOREPELLIN: A fragment (domain V) of perlecan, is of interest because it has anti-angiogenic features through binding to integrin α2β1, and may have an anti-cancer role



ENDOSOME: Specialized vesicular/tubular organelles with walls containing cholesterol (cf lysosome); possibly differing in specific roles, such as selection of the MHC class I or II pathway for loading soluble antigens; late endosomes have internal vesicular formation (exosomes) and the structures are called multivesicular bodies. Antibody linking with an antigen can influence the pathway taken by the receptor-complex.

Early endosome slightly acidic

Late endosome pH ~5.5-5.0

At <20oC, endosomes do not fuse with lysosomes



ENDOSTATIN: A COOH-terminal fragment of collagen XVIII with anti-angiogenic activity. It also blocks endothelial cell migration, induces apoptosis and cell cycle arrest,



ENDOTHELIN: A potent vasoconstrictor peptide; Endothelin-1 up-regulates CCN2 in fibroblasts



ENDOTHELIAL TIP: A transient phenotype, having extensive filipodia protrusions directed towards angiogenic attractants, with high levels of gene transcripts for VEGF & VEGFR2, and certain other expressed genes, such as pdgf-b. Cytokines show oscillations, with VEGF-A (pro-tip) countered by Dll4-Notch



ENDOTOXIN: A general term for intracellular, structural, bacterial toxins, which are retained within the bacterial cells until they disintegrate, being components of the cell wall and generally of a polymolecular, lipid-phospho-lipid-polysaccharide-protein complex, which can comprise some 5-10% of the dry weight of the cells. They can tolerate 100 oC. LPS can produce activate the NF-κB pathway within 40 min; See LPS



ENDOTOXIN TOLERANCE: A term used to describe the loss of response to LPS (eg by macrophages) after an initial dose - thought to be associated with activation of the macrophages. Ex vivo, it is short-lived (eg 24 h), but in vivo, it can last for weeks; this may increase the risk of infection during the interval – the biological features are poorly understood, and there may be neural signal involved in vivo; in mice, HT may shorten/lessen the 'endotoxin tolerance'



END5P: Yeast homologue of WIP (See also Verprolin/VRP1P)



ENGELBRETH-HOLM-SWARM TUMOUR: Tumours developed in ST/Eh strain mice that produce large amounts of basement membrane components into the medium, in particular, Laminin-1.



ENGRAFTMENT: Short-term (weeks/months) by differentiating progenitors. Long-term, multilineage engraftment requires stem cell lodgement into specialized niches.



ENHANCERS: Are transcription factor binding sites distal to the start site and above or below the promoter; they provide tissue specificity on promoter activity. Many are unable to function until the 2-cell embryo



ENO1: Gene for glycolytic Enolase, on 1p35-6 near gene for MBP-1 (may share transcripts). A 37 kDa protein alternatively translated from the α-enolase mRNA has the ability to repress transcription of the c-Myc P2 promoter



ENO2: Gene for γγ Enolase (NSE), Chromosome 12p13.



ENOLASE: Glycolytic enzyme, a dimer, with two identical sub-units which, catalyses

2-phospho-D-glycerate ⇔ phosphoenolpyruvate.

Enolase 1-3 isoenzymes. A(αα)-ENO is 49 kDa - a frequent target for autoimmune antibodies, but those against γγ are more specific for autoimmunity. It is moderately sensitive to oxidation and is said to show heat shock protein-like features. They have an absolute requirement for divalent cation, with Mg++ the most active - I 'conformational', allowing substrate admission/binding, the second II 'catalytic'. At high cation concentration, a postulated third site III can be occupied, and this is 'inhibitory', however, the inhibitory effect may arise by the requirement that the cation must leave the catalytic environment before the product can leave. Phosphonoacetohydroxamate is the most active inhibitor. There is an active loop Ser36-His43, setting the 'closed' configuration over the catalytic loop Val153-Phe169. His159 in hydrogen bond contact with substrate P (PGA) in one monomer; the other has water molecules and holds PEP. H20 comes/goes from/to Glu168 & Glu211, with the state of C2 crucial. There is a third loop Ser250-Glu277 that also moves. α-Enolase (47 kDa) is a component of Monocyte/DC-derived exosomes



eNOS: Endothelial nitric oxide synthase



ENOXAPARIN: A low molecular weight form of heparin; may reduce the Secretase produced proteolylic products from APP



ENPP1: Ecto-nucleotide pyrophosphatase/phosphodiesterase 1; involved in inhibiting the secretion of FGF23



En(sp1): Enhancer of Split



ENT1P & 2P: Epsin orthologues in S. cerevisiae



ENTACTIN-1 & -2: See Nidogens



ENTEROCYTE: The predominate epithelial cell of the inner lining of the gut; CXCL12 + Ca2+ increases enterocyte migration on laminin. CXCL12 activated laminin-specific integrins, as opposed to collagen IV-binding integrins; the expressed integrins being α3β1, α6β1, α6β4; these having different functions.



ENTH: Epsin-N-terminal homology; defined by the consensus sequence (D/E)ATx2(D/E)PWGP an highly conserved domain on epsin, ~140 aa, with key basic groups Arg8 Lys11 Arg25 Arg63 Lys69 His73 Arg114, all bar the last to be within puncta, the forming PtdIns(4,5)P2 binding site, providing electrostatic attraction, Leu6 & Met10 are needed for bilipid membrane penetration; Epsins with this are recruited by Eps15; refer Epsin & Clathrin



ENZALUTAMIDE: (MDV3100) A second generation anti-androgen



EOC: Epithelial ovarian cancer



EOMESODERMIN: See Eomes



EOMES: A T-box transcription factor that induces the expression of memory markers CD44 & CD122. It is not expressed in iNKT cells or CD4+ cells and it is involved in cytotoxicity and IFN-γ secretion by NK cells. SAP may induce



EOMESODERMIN: Transcription factor for CTL differentiation



EOTAXIN: ~8.4 kDa, 74 aa polypeptide, CC chemokine isolated from bronchoalveolar lavage fluid after ovalbumin challenge. Chemotactic for eosinophils. High identity with MCP-1 to 3. It has high selectivity for its receptor, and is probably the most relevant chemokine for allergic conditions and asthma



EP: E64D/Pepstatin; lysosomal protease inhibitor



EPB41: (Protein) 4.1R gene



EpCAM: Antigen of mTEC > cTEC; a colorectal cancer stem cell marker



EPCC: Electron-(hole-)phonon coupling constant; a quasi-particle, with charge and associated polarization field



EPCR: Endothelial protein C receptor



EPEC: Enteropathic E.coli



EPENDYMA: The layer of ciliated columnar cells that line the CNS ventricles and the central canal of the spinal cord. In the walls of the ventricles are specialized area where neural stem cells can generate progenitors within niches. Some of these cells integrate within the ependymal cell layer; large molecules can penetrate, because there are no tight junctions in the adult





EPH: Erythropoietin-producing hepatoma amplified sequence group: receptor tyrosine kinase



EPHRIN B2: A regulator of cell segregation

Ephrin-4A An axon guidance molecule

Ephrin-3B An axon guidance molecule



EPIBLAST: Identifiable at E4.5 in the mouse embryo; cells derived from the polarblasts; gives rise to all cell types of the developing embryo proper; FGF4/Erk may prime cells for differentiation



EPICAN: Minor HSPG



EPIDERMIN: A lantibiotic; binds to a cell wall precursor lipid component



EPIGALLOCATECHIN GALLATE: From Green Tea; binds to and inactivates Bcl-2



EPIGENETIC: Inherited factors other than the genetic code controlling the sequence of gene expression (eg imprinting, by methylation of cytosine residues or histone modification). There are about 60 genes that are imprinted (mainly maternal); this decides which gene, from which parent, will be transcribed, and ensures that genes from both parents are necessary: the male genes towards extra-embryonal tissue development, the maternal to embryonal organization.



EPIGENOTYPE: The imprinted gene pattern



EPILIGRIN: See Laminin-5



EpiSC: Epiblast stem cell; a cell derived from the implanted (mouse) embryo (on & after E5.5) and grown in vitro, still retaining pluripotency and being able to give rise to primordial germ cells, but requiring activin & FGF; unable to integrate into a pre-implantation embryo; differentiate if grown on ES cell culture media



EPISTEMOLOGICAL: Relating to the theory of the method or grounds of knowledge



EPITOPE SPREADING: (In MS) the ability of the patient/host to widen the initial sensitivity from one antigen (p85-99 of MBP) epitope to others



EPLIN: (Lima-1) Epithelial protein lost in neoplasm; enhances bundling of F-actin and inhibit depolymerization; dimeric form makes a link between E-cadherin/α-catenin complex and F-actin



EPR: Electron paramagnetic resonance spectroscopy



EPS15: EGFR-pathway substrate; involved in clathrin vesicle formation



EPS15R: EPS15-related protein



EPSC: Excitatory post synaptic current



EPSIN1 - 3 & R (see below): Epsins are monomeric, tubulating, clathrin-coated vesicle (CCV)-associated proteins that bind to vti1b and insert into the cytoplasmic leaflet of the plasma membrane bilayer, to separate the head groups of the outer layer(?). Epsin1 folds around the PtdIns(4,5)P2 molecules, exposing hydrophobic groups Leucine6 Methionine10 Isoleucine13 in the process. The PtdIns(4,5)P2 binding groups for Epsin ENTH are: Arginine7 & 8 Lysine11 Arginine25 Asparagine30 Arginine63 Lysine69 Histidine73

Recruits & phosphorylates Hip1r. Phosphorylated by Cdk1 in Mitosis.



EPSINR: Epsin-related protein (KIAA0171); related to the Drosophila homologue



EPTA: Ethanolic phosphotungstic acid. Used with Transmission Electron Microscopy. Does no detect clathrin coats



EQAS: External quality assurance scheme



ER: (a) Endoplasmic reticulum. Retention motif - KDEL. See also SR; up to ~1/3 of cellular proteins are synthesized within the ER

(b) Oestrogen(estrogen) receptor;

ERα can be phosphorylated at Ser167 & Ser118 in response to ERK signalling (eg by ERK &/or Akt); 25%of ER+/PR+ tumours, 66% of ER+/PR- tumours and 55% of ER-/PR+ tumours are resistant to Tamoxifen, or develop resistance



ERAD: Endoplasmic reticulum-associated degradation; ensures that only properly folded precursor channel proteins are accepted; two pathways

ERAD(I): Ubiquitin/proteosome pathway – for soluble proteins in the cytoplasm

ERAD(II): Autophagic/lysosomal – for insoluble protein aggregates



ERBB1: = EGFR



ERBB2: Oncogene for product Erbb2; See HER2



ErbB4: Belongs to EGF receptor family of receptor tyrosine kinases. There are 4 isoforms by different splicing. Nuclear localization in cancer cells is associated with a poor prognosis and cell processing involves surface HPSE



ERC: ELKS/Rab6-interacting protein/CAST



ERDJ4: A UPR target gene (see also GRP94 & GRP78); increases the activity of the chaperone GRP78



ERE: Oestrogen(oestrogen) response element



ERG: A member of the ETS family of transcription factors; a specific endothelial marker



ERG2:Yeast gene that encodes a sterol C8-C7 isomerase (with which many drugs bind)



ERGIC: ER-Golgi intermediate compartment



ERITORAN: An inhibitor of TLR4



ERK: Extracellular signal-regulated kinase - p42 & p44. Early kinase in the extrinsic 'stress' pathway leading to apoptosis via JNK; in vitro, Lithium causes an increase of phosphorylated (p-42) ERK at 4 h, lasting for 24 h, then declining



ERLIN-1 & -2: (SPFH1/2) ER lipid raft-associated proteins



ERLOTINIB: A tyrosine kinase inhibitor specific for the EGFR; can lead to a reduction of HIF-1α & VEGR expression, resulting in more normal vascularization within tumours, increased blood flow, oxygenation and better results from radiotherapy



ERM: Ezrin-radixin-moesin proteins; link F-actin to transmembrane receptors. The N-terminal of all is highly conserved



ERo1-Lα & -Lβ: ER oxidoreductase, requiring FAD; regulates Ca2+ flux; produce H2O2. ERo1-Lα is enriched at the MAMs. ERo1-Lβ tends to be found in cells that produce a large amount of protein



ERo1p: ER enzyme responsible for oxygen consumption in Yeast; glycosylated membrane-associated flavoprotein located on the luminal side



ERN1: See IREα1



ERp44: Member of a thiol redoxin family; ER luminal chaperone; regulates Ca2+ flux



ERp57: Member of a thiol redoxin family; ER luminal chaperone; regulates Ca2+ flux



ERSE1: Endoplasmic reticulum stress response element 1



ER-TR9: Marker for reticular fibroblasts; marginal zone macrophages in the spleen



ES: Embryonal (pluripotent) stem (cell); in mouse, from the inner cell mass of the blastocyst between day E3.5 - E4.5 (by E4.5 there are three germ cell types, trophectoderm, hypoblast and epiblast). ES to EpiES shows factor differences ─

Whilst Klf2, Klf4, Esrrb, Nr5a2, Tbx3, Rex1 & Nanog all decline, but not in unison ─

Klf4 falls rapidly on day 1

Esrrb falls by day 2

Klf2 drops ~50% day 2-3 then steady for 24 h

Rex1 drops ~50% day 2-3 then steady for 24 h

Nr5a2 slow decline (lost in EpiSC)

See mESC, ESC



ESA: Erythropoiesis-stimulating agent; when used to excess, the blood flow through tissues (eg tumours) may fall because of increased blood viscosity



ESC: Embryonal stem cell; pluripotent, immortal derived from the inner cell mass of mammalian blastocysts; see mESC for murine



ESCRT: Endosomal sorting complex required for transport; (0) I - III. Proteins that act sequentially to select proteins to retain within the internal vesicles. Involved with late endosomal/MVB development. The three are involved in cargo sorting and vesicle formation, probably sequentially I ⇒ II ⇒ III. ESCRT-I complex may be involved in certain retroviral budding pathways. ('p' indicates yeast nomenclature)

O Vps27p/Hrs (Hepatoycyte growth factor-regulated tyrosine kinase substrate)

Hse1p/STAM (Signal transducing adaptor molecule)

I Heterotrimeric, of

Vps23/Tsg101

Vps28p

Vps37p

II Heterotetrameric, of

Vps22p

Vps25p x 2

Vps36p. GLUE domain binds to PI3P

Mammalians may not be so dependent on the ESCRT II for receptor- sorting

III Vps20p; myristoylated, binds with Vps25p. It assembles on endosome membranes as a high order heteromultimer of Vps2p, -20p, -24p, -32p; disassembles by AAA ATPase Vps4p. By binding Bro1p/Vps31p, recruits the de-ubiquitinating enzyme Doa4p/AMSH. Vps24 can bind to phosphatidylinositol-3,5-bisphosphate, possibly allowing direct binding to endosomal membrane.



E-SELECTIN: Expressed by endothelial cells of some bone marrow venules (at least) in mice. Its association with SDF-1 may determine the homing of tumour cells. (See ELAM-1)



ESI: Electronic Supplementary Information



ESI-MS: Electron-spray ionization mass spectroscopy



ESOPE: European Standard Operating Procedures of Electrochemotherapy



ESR: (a) Erythrocyte Sedimentation Rate (Haematology)

(b) Electron spin resonance (Physical-chemistry - Check context)



ESR1: Oestogen receptor 1; see ERα; XBP1 can bind and activate in a ligand fashion



ESRD: End stage renal disease



ESRRB: Can confer LIF-independent self-renewal to ES cells



EST: Embryonic stem cell test



ESTs: Expressed sequence tags (ie DNA)



ET-1: Endothelin-1; promotes osteogenic differentiation and bone matrix formation & inhibits osteoclast activity



ETANERCEPT: Soluble receptor - blocks TNF-α receptor TNFR2 (and also blocks certain LT-α actions); a dimeric fusion protein with the extracellular
part of the human p75 TNFR linked to the Fc region of the human IgG1; administered by sc injection



EtBr: Ethidium bromide



EthD-1: Ethidium homodimer-1; 0.8 kDa; a membrane-impermeable DNA stain; cells fluorescing red when the plasma membrane is breached



ETHIDIUM BROMIDE/HOMODIMER: Binds to nucleic acid and can cause frame-shift mutations; agent that depletes mitochondrial DNA. It fluoresces,
and is used with acridine orange to differentiate viable/non-viable cells



ETK: Endothelial/epithelial tyrosine kinase (See also Bmx); associates with TNFR2



ETOPOSIDE: Complexes with topoisomerase II and DNA to enhance double-strand & single-strand cleavage of DNA. Blocks cell cycle in S & G2 &
induces apoptosis; creates genotoxic stress and can trigger necroptosis &/or apoptosis; causes depletion of cIAP with a spontaneous assemblage of the ripoptosome



ETP: (a) Early thymic progenitor; have high level of KIT expression; potential for T-cell, NK & DCs (possibly also B cells very early in the thymus, but potential lost)

(b) Etoposide



ETS: Erythroblast transformation specific; a family of key transcription regulators of angiogenesis, vasculogenesis and heparanase activity; ETS1, ETS2, PEA3 & ER81. Ets1 controls the transcription of Cathepsin B, and is probably involved in SERCA activation in EC



EUBACTERIA: Bacteria with nuclei



EUCHROMATIN: Tightly packed DNA, RNA & histone protein, ~92% of human genome; has gene concentration (but is less tightly packed & takes less stain) & is frequently actively transcribing



EUKARYOTE: Cells with nuclei



EUTHERIAN: Member of placental mammals

Eu-TTA: A temperature indicator; produces phosphorescence



EVD: Ebola viral disease



EVEROLIMUS: An mTOR inhibitor; a derivative of sirolimus; considered to be an immune suppressant and used to prevent organ transplant rejection; also has anti-tumour actions (renal cell cancer etc.); has selective action against the mTORC1 protein complex, allowing hyperactivation of Akt, encouraging cell survival



EVH1: Enabled/VASP homology 1



E Vps: Ubiquitin vacuolar protein sorting family involved with MVBs; ~17 gene members (eg ESCRT)



EWING'S 'SARCOMA': (James Ewing, USA, Pathologist, 1866-1943) A primitive neuroectodermal, small-cell tumour usually of bones in young adults. The cells have small nuclei, the cells occurring in solid sheets & cords, with regressive and necrotic changes; the cytoplasm typically contains much glycogen (demonstration requiring frozen section); they grow rapidly (see EFT)



Exas: Ascites-derived exosomes



EXCITOTOXICITY: A toxicity produced as a result of excessive Ca2+ entering cells brought about by glutamate or N-methyl-D-aspartate, producing excessive cellular responses; the toxicity is blocked by Nec-1



ExE: Extraembryonic endoderm



EXENCEPHALY: Failure of the rostral end of the neural plate/tube to close; intact cilia seem involved as is the Hedgehog pathway



EXOCYTOSIS: The delivery of intracellular vesicles to the plasma membrane, fusion, and discharge of the vesicle contents outside the cell.



EXOSOME: Small vesicles created within multi-vesicular bodies, and then released upon fusion of the latter's limiting membrane with the plasma membrane; found in many cell types. The only known physiological targets are the myeloid (endocytosis) & follicular dendritic cell (adherence). They have common characteristics:

Bi-lipid limiting membrane

50-100 nm diameter

Floatation 1.13-1.21 g/mL on sucrose gradient

Restricted set of proteins

Associated with endocytic pathway

Those produced by different cells may have distinct characteristics of the cell of origin. They are only produced by living cells and differ from the micro-vesicles produced by apoptosis. The lipid components are mobile and 'flip-flop' in orientation, reducing asymmetry across the membrane. Phospholipase D2 is enriched, and may signal. Immature DCs have MVBs and produce exosomes (0.5 mg/million DC) with both MHC class I & II peptide complexes, mature DCs decrease production x 2-3 times (0.2 mg/million DC), with qualitative differences. ICAM-1/CD54 seems indispensable for efficient signalling, and is produced by mature DCs (with stimulation). Exosomes from mature DCs are 50-100 more potent at inducing CD4+ T cell proliferation than from immature DCs. Those from immature DCs can activate NK cells for anti-tumour activity. Co-stimulatory molecules (eg B7.2) are not included in the exosomes, but are generally needed for exosome stimulatory effect

Feature

Immature

Mature

Floatation 1 g/ml

1.148 ~ 1.182

1.166 > 1.185

PEP

? band loss ~64 kDa

? band gain ~22 kDa

T cell activation

x1

x50 - 100

ICAM-1

-

+++

B7.2

+

++++

MHC-II

++

+++

MFG-E8

++++

++

Tsg101

++

+

MHC-I

++

+



Ribosomal proteins are reported present



EXOSTOCIN 1/2: Two Golgi enzymes involved in proteoglycan (eg Heparan) formation



EXPORTIN-1: Involved in the movement of Cdc25B out of the nucleus



EXT1/2: Genes that encode Glycosyltransferases responsible for Heparan sulphate polymerization. Mutations may result in hereditary multiple exostoses (autosomal dominant); homologous with tout velu



EXT1/2: Exostocin 1/2. Two Golgi enzymes involved in proteoglycan (eg Heparan) formation. They form a hetero-oligomeric complex and are involved in chain elongation



EXTEIN: Excised protein sequences on either side of an intein, to be spliced together in a self catalytic manner to create a new product. (See intein.)



EXTRACELLULAR MATRIX: Usually relating to proteoglycans and needs specific definition in context. In some in vitro experiments, it is the material obtained from washed adherent cells with isotonic trypsin. Cell-bound proteoglycan (eg syndecan) can be expected to be split off the plasma membrane



EXTRACELLULAR REDOX: Normally oxidative; reduced HMGB1 would be expected to be oxidized unless reducing conditions provided by cysteine & redox enzymes, may generate or prolong reduced HMGB1



EXTS: Exostocin



ex vivo: separated from a living organism (eg cells in a Petri dish)



EYFP: Enhanced yellow fluorescent protein



EZF-2: Endothelial zinc finger protein-2; a novel transcription factor, and a major regulator of SREC transcription



EZH2: Zeste homologue 2 gene



EZRIN: 80 kDa; Assists the maturation and the development of long apical microvilli in the RPE. Associates with Radixin and is a cortical cytoskeletal protein; links cortical actin filaments with the plasm cell membrane; associates with Fas and inhibits responses through Fas



f1: (B-50); See GAP-43



F4/80: Pan-Macrophage marker (mouse). The thymic cortical F4/80 APCs may be similar to the human DC- SIGN+ APCs



FA: (a) Focal adhesion

(b) Fatty acid; less inclined than FAEE to stimulate Ca2+ from stores, rather, they inhibit mitochondrial ATP synthesis and depress Ca2+-ATP pump activity (eg SERCA)



FA.11: Macrophage marker



FACE: Fluorophore assisted carbohydrate electrophoresis



FACS: Fluorescence-activated cell sorting



F-ACTIN: Filamentous actin



FAD: (a) Familial Alzheimer's Disease

(b) Flavin adenine dinucleotide; a cofactor; made from riboflavin in the mitochondrial matrix by FAD synthetase; deficiencies within the mitochondria impact upon the ER enzyme function



FADD: (Mort1) Fas-associated death domain. Part of the TRAIL pathway. FADD has its own death domain



FAEE: Fatty acid ethyl ester; non-oxidative product of alcohol and fatty acids. These induce trypsin activation and vacuole formation of zymogen granules and elicit sustained [Ca2+]i elevations



FAK: p125FAK; a GPCR-regulated tyrosine phosphoprotein. Focal adhesion kinase; undergoes tyrosine phosphorylation after binding β-integrin and provides a docking site for several signalling proteins, including Grb2. Its activation involves displacing a FERM group that has been sequestering the key Y397 from autophosphorylation, which can then proceed. It is involved in remodelling the actin cytoskeleton and locomotion



FALS: Familial Amyotrophic lateral sclerosis (10%). At least 10 gene mutation loci in 6 genes have been mapped: ALS1-8, ALS with fronto-temporal dementia & ALS with Parkinsonism & dementia. ALS1 (20% FALS) involves SOD1 at 21q22.21, the gene for Superoxide dismutase. ALS8 – 20q13.3



FAM129B: A melanoma-associated gene that modulates Wnt/β-catenin signalling



FAM129B: A protein with 746 aa, a differentially phosphorylated C-terminal domain and an N-terminal pleckstrin homology domain; no known enzyme function; known to inhibit TNF-induced apoptosis in HeLa cells; malignant melanoma cells express it and it encourages invasion in vitro; is phosphorylated following MEK activation; seems to promote Wnt signalling in melanoma cells, and loss decreases apoptosis involving Wnt; FAM129B reduction in HeLa cells challenged with (TNF + cyclohexamide) showed increased apoptosis (as yet unexplained)



FAM-FFCK: A fluorescently-labelled TPCK derivative



FAN: Factor associated with nSMase; an adapter protein required for the TNF-α activation of nSMase



FANCD2: Fanconi anaemia complementing D2. Involved in the detection/repair of DNA damage: Independent of Brca2 & Rad51



FANO FACTOR: The variance over the mean of the number of photoelectrons within the observation time T



FAP: Familial adenosis coli. See APC



Fa1p: A protein involved in regulating detachment of flagella from basal bodies



Fa2p: An homologue of Nek2



Fas: A transmembrane receptor (See CD95) of the TNF receptor superfamily at start of extrinsic apoptosis cascade; 36 kDa & broadly expressed. When activated by Fas ligand, a Fas-microtubule association of GD3 commences within 15 min, ganglioside GD3 reaching the mitochondria at ~60 min.; it recruits FADD. Fas+FADD's death domain attracts the binding of Caspase 8 to FADD at the DED. This activates Caspase 8. p53 increases Fas movement from the Golgi and activates Fas-FADD activity. A single bolus of alcohol to mice, results in Fas-induced hepatocyte apoptosis



FASCIN: A negative regulator of epithelial adherens junctions



FasL: See Fas ligand



FASLG: Fas ligand



Fas Ligand: The signal protein that targets Fas and initiates response by trimerization of Fas; 40 kDa, glycosylated; expressed by activated lymphocytes, NK cells, Sertoli cells, & cells of the eye, liver, kidney & some tumour cells; activation of Fas(R) results in apoptosis. FasL on micro-vesicular exosomes may be important in preventing placental rejection



FasR: Fas ligand receptor



FAT: focal adhesion targeting



FAT1: An atypical cadherin; interacts with Caspase-8, preventing it from joining the DISC signalling complex and blocking Caspase-8 apoptosis

FAT4: A cadherin-related molecule with 34 cadherin repeats; does not interact with other cells, but with Dachsous on the same cell; seems to be a tumour represser; involves the Hippo pathway



FBA: Flux balance analysis



F-1,6-BP: Fructose-1,6-bisphosphate. An homotetramer, subunits 337 aa. A target for Lithium, see Bpnt1



FBS: Foetal bovine serum; has an anti-apoptotic effect against the Fas/L stimulus



FC: (a) Focal complex; immature adhesion sites, formed of a complex of ligand+integrins+adaptor & signalling proteins, maturing to FAs

(b) Fibrocystic (eg breast)



FCAS: Familial cold auto-inflammatory syndrome; NLRP3 mutation L353P; see CAPS



FCCP: Carbonylcyanide p-(Triflourmethoxy) phenylhydrazone; releases mitochondrial Ca2+



FcγR: Ig receptors with the common Ig γ chain; the main regulators of inflammation by immune complexes; in mice :

FcγRI: receptor with an high affinity for monomeric IgG2a

FcγRII & III: interact preferentially with IgG1, IgG2a and IgG2b; FcγRIIb is inhibitory on BCR (see below)

FcγRI & FcγRIII are multimeric complexes; the γ chain includes an activating immune receptor tyrosine activation motif (ITAM). Binding to these stimulates phagocytosis by macrophages, antibody dependent cell-mediated cytotoxicity by NK cells and mast cell degranulation.

FcγRII has one α chain containing an inhibitory immune receptor tyrosine inhibition motif (ITIM). It has 4 isoforms & ligation is generally inhibitory. Myeloid cells express FcγRIIb2 isoform, mediating endocytosis of immune complexes and Ag presentation, but down-regulates macrophages.

Uptake of antibody+ immune complexes by mouse splenic CD8+ & CD8- DCs is via the Complement receptors



FCHo2: FCH domain-only protein 2. Involved in clathrin vesicle formation and fusion for syncytium



FCN: Fucoidan



FCR: Fractional catabolic rate



FCS: Foetal calf serum; frequently added to cell culture media (~10%) as a non-specific growth factor; it interferes with cholesterol



FDA: Fluorescein diacetate; a fluorescent stain for living cells



FDC: Follicular dendritic cells (of lymphoid tissue)



FDR: False discovery rate



FDG: Fluorodeoxyglucose



FDGC: Familial diffuse gastric cancer



FDR: (a) Fisher's discrimination ratio

(b) False Discovery Rate



FDTD: Finite difference time domain



FE: (a) FRET efficiency; a statistical assessment

(b) Fixed effect



FEAR-OF-INTIMACY: A zinc transporter that controls cell migration



FEEL-1, -2: Fasciclin, EGF-like, laminin-type EGF-like and link domain-containing scavenger receptor-1/-2. FEEL-1 is 2570 aa. Only FEEL-1 (=stabilin-1, hyaluronan scavenger receptor, HA/S-R) is expressed by CD14+ mononuclear cells and vascular endothelial cells. Both are endocytic AGE receptors. (See CLEVER.) They may play an important role in malignant cell direction in lymphatic vessels. FEEL-2 may be a receptor (HARE) for Hyaluronan and Chondroitin. Both FEEL-1 & -2 may be important in clearing waste materials from the blood and lymph



FEM: Finite element model



FENOFIBRATE: Enhances SR-BI degradation in post ER compartments



FENTON REACTION: Fe2+ + H2O2 => Fe3+ + OH¯ + .OH (the production of the very oxidizing, hydroxyl radical). Ascorbate may permit the reverse reaction – a pro-oxidant role



FERM DOMAIN: A domain found in protein 4.1, being a 'genetically mobile' motif and found in others with membrane binding (protein & lipid), such as, ezrin, radixin, merlin, moesin, some tyrosine phosphatases, talin and some other metazoan & plant proteins. It has 3 lobes, NH2-terminal has an ubiquitin-like fold, central is a binding site like acetyl-CoA-binding protein and COOH-terminal is similar to PH/phosphotyrosine binding protein. The lobes do not seem to behave independently. It binds with a range of transmembrane proteins, including CD44, calmodulin and 2,3-diphosphoglycerate. The ion exchanger AE1 binds at LEEDY in the NH2-terminal lobe



FERRITIN: A ferrous iron-storage protein; capable of storing 4,500 atoms of iron/molecule, but normally only ~20% saturated; complexing molecules of redox-active molecules can release the iron from ferritin (eg thiols, ascorbate or reduced flavins) but excessive release can cause the production of HO*, which can be damaging; circulating levels can be found in childhood Hodgkin's lymphoma, and is considered a bad prognostic feature; ferritin, and other large molecule, may be able to penetrate endothelial barriers around tumours and may provide the iron to support the pro-oxidant role of ascorbate, in some circumstances, the ascorbate may bring about the release of the iron from the ferritin (and possibly other protein chelates)



FEVER: Generally considered to be 37.5 oC and above in adult humans, but can be modified by age and circumstances. When brought on by microbiological sepsis or infection; released toxins of the endotoxin type (eg LPS) involving COX2 and PGE2 from macrophages result in the host elevating the 'set point' for temperature control (cf hyperthermia, where the 'set point' is unchanged). This response is highly conserved, and has been associated with a better survival rate; temperatures of ~39.5 oC can increase serum TNF (x3, largely from liver), IL-6 (x4, x15 in liver, but also other major organs) and reduced 'endotoxin tolerance', with increased phosphorylation of IKK, IκB and NF-κB, and the latter's subsequent nuclear relocation; the results can be pro-inflammatory & anti-inflammatory depending on circumstances; the benefits of fever may only be of value if the subject is not likely to develop an energy deficit; in addition to skeletal muscle shivering, there is induced 'heat-seeking' behaviour, meaning that the temperature rise may depend upon the environmental assistance for the change; see also Hyperthermia, Macrophage & Hsf-1



FFAT: An amino acid motif present in Nir1-3, used for attachment of the VAPs



FFE: Free flow electrophoresis



FFP-18: A fluorescent dye used to measure intracellular Ca2+. It requires permeabilization and is attached to membranes, the plasma and nuclear membranes



FFPE: Formalin-fixed paraffin embedded (histology preparation)



FFS: Failure-free survival



FGE: Formylglycine-generating enzyme(s)



FGF: Human Genes/Chromosomes

FGF1: 5q31.3

FGF2: 4q27

FGF3: 11q13.3

FGF4:11q13.3

FGF5: 4q21.21

FGF6: 12p13.32

FGF7: 15q21.2

FGF8: 10q24.32

FGF9: 13q12.11

FGF10: 5p12

FGF11: 17p13.1

FGF12: 3q28

FGF13: Xq26.3

FGF14: 13q33.1

FGF15: - The gene homologous to the mouse FGF15 is FGF19

FGF16: Xq21.1

FGF17: 8p21.3

FGF18: 5q35.1

FGF19: 11q13.3

FGF20: 8p22

FGF21: 19q13.32

FGF22: 19p13.3

FGF23: 12p12.32



FGF-1 to 23: Fibroblast growth factors; some are heparin-binding, those that do may depend upon HS for tissue specificity and translocation to the nucleus. They have angiogenic influences and stimulate most tumour cells. All have a conserved domain of 120 aa which shows 16-65 sequence identity, some, the paracrine-acting members (not the FGF19 subfamily) have a Heparin-binding motif GxxxxGxxT/S

FGF-1: = acidic FGF; FGF-1 & -2 are more potent angiogenic factors than VEGF

FGF-2: = basic FGF; acts mainly on mesenchymal and neuroectodermal cells; binds strongly to heparan in the epidermal basement membrane

FGF-3 (INT2): Acts on epithelial cells

FGF-4: A stimulation factor of embryonal stem cells; when Heparan sulphate as co-receptor and the FGFR signals, embryonal stem cells are held in a primed heterogenous state of dynamic factor oscillations, poised for differentiation; without the signal ESCs are more easily cultured, persisting in the naive state (Nanogpos)

FGF-5: A marker for primitive ectoderm

FGF-7 (=KGF): 28 kDa; 5 cysteinyl residues (only C40 free but structural) and binds Heparin, which stabilizes it; targets keratinocytes, gastrointestinal and transitional epithelia and type II pneumocytes, produced by endothelial cells, fibroblasts and dendritic T cells in response to inflammation and associates with activin, with a similar production pattern; stimulates proliferation and migration; fails to bind to heparan in the epidermal basement membrane; considered to be a phosphatonin, having been extracted from TIO tumours; activates FGFR2IIIb (as do FGF1 & 10); in mouse skin wound healing, FGF7 mRNA shows a major peak at ~2 d, and a lesser peak at ~15 d (FGF10 is similar, FGF23 lacks the second peak). Interestingly, whilst many cancer express FGFR2IIIb, the administration of FGF7 does not seem to increase tumour growth (perhaps this could be due to the tumour cells lacking heparan quality/quantity in their coats); it was thought to bind to CS-B (dermatan sulphate), but in vitro interaction seems weak (as with CS-D & CS-E); said to protect cells from ROS. Unstable in vitro, showing aggregation, in 10 mM sodium phosphate buffer & 140 mM NaCl pH7, 0.5 mg/mL showed a half-life at 37oC of ~1.5 d

FGF-8: Mutation results in loss of function and Kalmann's syndrome

FGF-10: =KGF2; Stimulates FGFR2IIIb; loss of function gives rise to LADD's syndrome

FGF-13: =FHF2

FGF-18: Stimulated proliferation of cultured osteoblasts & chondroblasts, but inhibited their differentiation

FGF-19: holds a subfamily:

FGF-15, FGF-19, FGF-21 & FGF-23

These have little or no affinity for heparin, and the suggestion is that, by not binding to heparin (or heparin-like groups) the factors are more easily dispersed in the blood stream to induce actions at a distance from production

FGF-21: Mainly produced in the liver, but targets adipose tissue

FGF-23: 251 aa, 32 kDa, with a specific 72 aa C-terminal fragment; can be split between R179 & S180 to produce fragments of uncertain significance; contains a pro-convertase processing site; has a furin-like pro-protein convertase recognition site; predominantly expressed in bone (particularly osteocytes; see DMP1, MEPE), also pericyte-like cells around venous sinuses in the marrow, lateral ventrical/choroid & thymus; can interact with other FGF members' receptors (FGFR1-3 & FGFR4, with FGFR1 [iiic] the main); specificity for the target tissue is determined by the presence of the co-receptor KLOTHO; expression in osteocytes is influenced by 1,24(OH)2vit D3 & phosphate, the former raising the serum level of FGF23 and suppressing PHEX mRNA, with a resulting rise in FGF23; dietary & serum phosphate raise the FGF23 level; PTH/receptor raise the serum level; suppresses transporters that mediate renal proximal tubule uptake of phosphate via αKLOTHO, FGFR1, ERK1/2 & SGK1 & suppresses 1α-hydroxylase (suppresses Vit D activation), involving phosphorylation of NHERF1 at S77, with loss of NaLi-IIa/NHERF1 complex at the cell membrane; Possibly the most important regulator of serum phosphate and calcitriol [1,25(OH2)D3] being secreted by osteocytes & osteoblasts and its level increases as chronic kidney disease worsens (cause unclear), is a mortality risk factor and may be involved in secondary hyperparathyroidism; inhibits 1α-hydroxylase; in wounded skin of mice, FGF23 mRNA peaks at about 2 d (as with FGF7); mouse in vitro p-ERK activity from injected FGF23 peaks at ~10 min and goes by ~60 min; the proximal tubule secondary effects respond by 30 min to hours



FgfR-1 to 4: Fibroblast growth factor receptor - a family; the extracellular ligand-binding domain is of 3 Ig-like domains (D1-3). Glycosylated by the TGN before membrane siting; activation requires dimerization and heparan/heparin sulphate is a co-factor. The HSPG can link adjacent ternary complexes. Alternate splicing creates variations in specificity: FGFR2 IIIb binds FGF7 & FGF1 > FGF2; also FGF10; FGFR1 is probably involved in granulation tissue formation and the dermal regrowth; FGFR3 seems important in bone repair



FGly: Formylglycine; essential for the function of Sulphatases (aryl sulfamates may target it for inhibition)



FGR: Foetal growth restriction



FHA: Phenylalanine - Histidine - Alanine. A phosphor-amino acid binding motif



FHA: Forkhead-associated domain



FHC: Ferritin heavy chain; suppresses ROS by iron sequestration



FHCK: Familial hyperCK-aemia; an hereditary form of muscular dystrophy muscle fibres lack Cav3 at the plasma membrane due to a block at the Golgi; there is an inability for the plasma membrane to accommodate stretching



FHF: FGF homologous factor

FHF2: FGF-homologous factor-2; FGF-13



FHH: Familial hypocalciuric hypercalcaemia



FHIT: Fragile Histidine Triad; gene for a tumour suppressor in many epithelial cell types; suppressed by PI3K and Akt, the latter operating through FOXO transcription factors



FI: Functional interaction (network)



FIBRILLARIN: A nucleolar resident protein



FIBRONECTIN: An extracellular matrix component to which cells can attach; integrin α5β1, being the main fibronectin receptor; frequently coated onto plastic culture plates to assist cellular attachment



FIBROUS GRANULES: Electron dense, non-membranous granules ~ 70-100 nm in diam., probably the same as satellites. They have a central fibrous, dense core, surrounded by a corona. They seem to be precursors for deuterosomes, basal bodies and procentrioles, appearing in association with such structures and contributing to the growth of the latter. Some may be intranuclear, and some may pass from the nucleus to the cytoplasm.



FIDS: Focal isolated demyelinating syndrome



filaggrin: Gene for Ichthyosis vulgaris



FILIPIN: (Comes as a complex or as Filipin III); From Streptomyces filipensis. Binds to cholesterol



FIMBRIN: Has lateral associations with actin filaments



FIP200: Focal adhesion kinase family interacting protein; part of a complex involved in the initiation of an autophagosome



FiRE: FGF-inducible response element; a FGF-inducible Syndecan-1 transcription enhancer



FIS1: A mitochondrial membrane-bound protein that may be involved in mitochondrial shaping



FIS-1-Bap31: A complex believed to affect the ER-Mitochondrial relationship



FISETIN: (3,7,3',4'-tetrahydroxyflavone) A flavonol; on prostate and lung cancer cells, it inhibits PI3K/Akt & mTOR pathways



FISH: Fluorescent in situ hybridization



FISP-12: See CTGF



F2-ISOPROSTANE: A biomarker for lipid peroxidation in vivo



FIT: Finite integration technique



FITC: Fluorescein 5(6)-isothiocyanate; a fluorescent tag for proteins to be studied



FITC-VAD-fmk: FITC + Valine-Alanine-Glutamate-fluoromethylketone; specific for the active site of caspases



FK506: Tacrolimus; similar actions to Cyclosporin A



FKBP: FK-binding protein; binds to, and is inhibited by FK-506. It catalyses isomerization of Prolyl-peptide bonds

FKBP12: The protein receptor for everolimus, which interacts with mTORC1, inhibiting its signaling



FKH: Forkhead family of proteins, with over 80 members; DNA-binding factors. They control lineage commitment and developmental differentiation, with the ability to bind to a variety of sequences, usually closely associated with NFAT-binding sites.



FKHRL1: Insulin regulated transcription factor



FKN: Fractalkine



FL: Follicular lymphoma



FLA3: Encodes the KAP subunit of Kinesin II in Chlamydomonas. Fla10 protein does not localize to the basal body region properly in fla3 mutant cells. Motor subunits (FLA8&10) require wild-type Fla3 to affect chromosome segregation



FLA10: Subunit of the heterotrimeric Kinesin, described in Chlamydomonas. Phenotype fla10 is an heat sensitive mutant.



Fla-10: Gene for flagella assembly in Chlamydomonas



FLAG (System): A recombinant protein expression system using a short hydrophilic 8-amino acid peptide (Asp-Tyr-Lys-Asp-Asp-Asp-Asp-Lys) which is attached to the protein of interest. The FLAG peptide has a number of binding sites for specific monoclonal antibodies. The hydrophilic nature tends to hold the peptide in positions where it is exposed to the monoclonal antibodies



FLAP: 5-Lipoxygenase-activating protein



FLAVOBACTERIUM: Now Pedobacter



FLAVONOIDS: Categorized into Flavonols, Flavones, Catechins, Flavonones, Anthocyanidins



FLICE: FADD-like IL-1β-converting enzyme; See cFLIP



FLICE-LIKE: An intracellular anti-apototic inhibitory protein



FLIM: Fluorescence lifetime imaging microscopy



FLIP: c-FLICE-inhibitory protein; has 2 forms, FLIPS (short) & FLIPL (long); FLIPL is like Caspase 8 but is inactive because of an aa change; with
recruitment to the DISC, it can partially block the activation of Caspase-8; blocks Fas-induced apoptosis



FLIP: (a) Fluorescent loss in photo-bleaching. Assess the reforming of the fluorescent molecule

(b) c-FLICE-inhibitory protein; has 2 forms, FLIPS (short) & FLIPL (long); FLIPL is like Caspase 8 but is inactive because of an aa change;
with recruitment to the DISC, it can partially block the activation of Caspase-8; blocks Fas-induced apoptosis; can be induced by NF-κB



FLIPASE: ATPase II



FLIPR: Fluorometric Imaging Plate Reader; a machine for measuring materials such as Ca2+ fluorometrically



FLIPPASES: Enzymes that pump phospholipid from one leaflet of the bilayer to the other and can deform membranes by creating an imbalance in the
phospholipid number between the two leaflets. They work with coat proteins to form vesicles.