Caspase Activated DNase, 40 kDa, is an apoptosis-specific endonuclease that cleaves DNA into the observed olignucleosomal fragments. CAD is a cytoplasmic protein containing a NLS, and it is normally associated with its inhibitor ICAD. The CAD/ICAD complex is inactive, but during apoptosis Caspase-3 cleaves ICAD, CAD is released and enters the nucleus and degrades chromosomal DNA. ICAD is not just inhibitor but also chaperone for CAD, since active CAD is only expressed in presence of ICAD. For a review see Nagata, 2000, Exp. Cell Res. 256: 12-18.
Chlamydia protein Associating with Death Domains (CADD) was identified by database analysis as a DD-containing protein in Chlamydia. CADD strongly induces apoptosis upon overexpression in HeLa, Jurkat, Hep3B cells. CADD interacts with Fas, DR4, DR5, and weakly with TNFR1 but not FADD, RIP, RAIDD, and cFLIP. CADD is expressed late in the infectious cycle of Chlamydia trachomatis. Chlamydia species can either suppress or induce apoptosis, and CADD may modulate the apoptosis pathways of infected cells, thus revealing a new mechanism of host-pathogen interaction (Stenner-Liewen et al., 2002, JBC, 9633-9636).
Alteration of intracellular Ca2+ concentration can result in cell death under certain circumstances, although the role of intracellular free calcium in apoptotic events has been highly controversial. More...
Cancer is a term for a malignant tumor, i.e. an uncontrolled growing mass of abnormal cells that have the ability to invade surrounding tissue.
Malignant tumors arising from epithelial cells are termed carcinomas.
CAspase Recruitment Domains (CARDs) have been proposed to mediate the recruitment of caspases. CARDs are found in several caspases, e.g. CED-3, Caspase-1, Caspase-2, Caspase-8 and Caspase-9, but also Apaf-1. The DEDs are a specific example for CARDs.
CARD12 is a human member of the CED4/Apaf-1 family which contains a CARD domain and a central nucleotide binding site. CARD12 induces apoptosis upon overexpression and interacts with ASC. Moreover, CARD12 coprecipitates with caspase-1 (Geddes et al., 2001, Biochem. Biophys. Res. Comm., 284: 77-82).
Cystein Aspartate-specific Proteases: Caspases form a proteolytic network that is of central importance in the initiation and execution of the apoptotic program. More...
CBP / p300
CBP/p300 (CBP = CREB-binding protein) is a histone acetyltransferase. CBP can be phosphorylated by the cyclinE-Cdk2 complex, and by this CBP is activated. The CBP enzymatic activity might result in the activation of S-phase-gene expression and might contribute to G1/S transition. CBP is also target of the transforming protein E1A which binds to CBP: bound E1A renders CPB constitutively active. CBP is a co-activator for E2F and the RelA protein and it is a coactivator for p53-dependent transactivation and- repression.
CD40 is involved in regulating T-cell-dependent B-cell activation. Besides on B cells, macrophages and dendritic cells, CD40 is found on endothelial cells and fibroblasts where it appears to regulate inflammatory cytokine production (e.g via NF-kB) and cell adhesion. There is also evidence for CD40 being involved in regulating normal epithelial cell growth and differentiation, and CD40 might have an impact on the growth and sensitivity to apoptosis of carcinoma cells.
Cdc25 is an essential regulator of mitosis: it is a nuclear phosphatase which normally dephosphorylates and activates its substrate, the cyclin B/Cdc2 kinase. Dephosphorylation of cyclinB/Cdc2 initiates mitosis. Upon DNA damage, Cdc25 is phosphorylated by the Chk1 serine/threonine kinase and subsequently sequestered into the cytosol by Rad24: cyclinB/Cdc2 remains inactivated and the cell cycle is arrested in the G2 phase.
Cdc42 belongs to the rho/rac family of small G proteins and is upregulated by p53. Cdc42 can activate JNK1/SAPK which phosphorylate and thus inactivate Bcl-2, sensitizing cells to undergo apoptosis (Thomas et al., 2000, Oncogene, 19: 5259-69).
CED-3 CED-3 is the C.elegans caspase; besides CED-4 and CED-9 it plays a central role in C.elegans apoptosis. More...
CED-4 activates CED-3 in C.elegans, and it is regulated by CED-9. Its mammalian homolog is Apaf-1; More...
CED-9 is a pro-survival member of the Bcl-2 family: it is a crucial regulator of apoptosis in C.elegans. More...
In vitro systems in which apoptotic pathways and mechanisms can be studied by reconstitution of cytoplasmic extracts, isolated nuclei or mitochondria. It was shown that cytoplasmic extracts contain a main part of the apoptotic machinery that can e.g. induce apoptotic event in nuclei. Using cell-free systems it is possible to selectively activate certain apoptotic pathways such as the cytochrome c pathway or to study the impact of certain factors on the execution of apoptosis in the system (e.g. inhibitors, inducers ...). For an introduction and kind of a review about the application of cell-free systems reported in the literature click here.
Ceramide (N-Acyl-Sphingosine) is the precuror of sphingophospholipids which are part of the cell membrane, especially in neuronal cells. A number of studies reported that extracellular stimuli (e.g. TNF alpha, FasL, gamma irradiation and others) cause the activation of sphingomyelinase (SMase) and thereby the release of ceramide as a second messenger of apoptosis (Hannun, 1996, Science 274:1855-1859). Still, the role of ceramide as a second messenger in apoptosis has been controversely discussed (Hofmann and Dixit, 1998, TiBS 23: 374-377). More...
Chemoprevention is the use of pharmacologic or natural agents that inhibit the development of invasive cancer either by blocking the DNA damage that initiates carcinogenesis or by arresting or reversing the progression of premalignant cells in which such damage has already occurred (for Review see Hong and Sporn, 1997, Science, 278: 1073).
CIDE-A and CIDE-B
Cell death-Inducing DFF-45 Effectors CIDE-A and CIDE-B are highly related proteins displaying homology to the N-terminal CIDE-N region of DFF45/ICAD. Overexpression of CIDE-A and -B results in apoptosis which can be inhibited by DFF45. The C-terminal region of CIDE-A was shown to be necessary and sufficient for killing whereas the CIDE-N domain is required for DFF45 to inhibit CIDE-A-induced apoptosis. Thus, CIDE-A and -B were proposed to be DFF45-inhibitable effectors that promote cell death and DNA fragmentation (Inohara et al., 1998, EMBO J. 17, 2526-33). CIDE-B localizes in the mitochondria (Chen et al, 2000, JBC 275(30), 22619-22) and its N-terminus shows a bipolar property consisting of two oppositely charged regions which form a weak interaction interface functioning as a regulatory domain for DNA fragmentation pathways in apoptosis. (Lugovkoy et al., 1999, Cell 99, 747-55).
Cyclooxygenase-2 (COX-2), a key enzyme in the formation of prostaglandins from arachidonic acid. Upregulation of COX-2 appears to be a central event in colon carcinogenesis. COX-2 levels are increased in many primary human colon cancers and colon cancer cell lines; the mechanisms by which an increase in COX-2 activity promotes tumor formation are not entirely clear although suppression of apoptosis appears to be contributory (Prescott and White, 1996, Cell, 87: 783, Hong and Sporn, 2000, Science, 278: 1073).
Cps-6 is the C.elegans homologue of human mitochondrial endonuclease G, endo G. The cps-6 protein product also localizes to mitochondria and it is the first mitochondrial protein identified in C.elegans to be involved in PCD (Parrish et al., 2001, Nature, 412: 90-94).
cAMP-responsive element binding protein.
Cytokine response-modifier protein produced by cowpox virus: CrmA is a caspase-inhibitor for ICE family members, inhibits preferentially Caspase-1 but also Caspase-8; CrmA shows homology to serpins, a family of serine protease inhibitors. More...
Besides CED-3, Csp1 and Csp-2 are two other caspases in C. elegans with long prodomains (Shaham, 1998, JBC, 273: 35109-35117).
The Cellular Stress Response (CSR) gene contains a p53-binding site in intron 2 and thus might be regulated by p53.
Cyclin G was identified as a transcriptional target of p53 and was observed to be rapidly induced after gamma irradiation in mouse embryonic fibroblasts (MEFs). However, the function of Cyclin G remains unclear (Shimizu A et al., 1998, Biochem Biophys Res Commun. 242(3):529-33).
Cyp D is a cyclosporin A binding protein and is located in the mitochondrial membrane; it is part of the PT pore.
Cytochrome c is released from the mitochondria following the induction of apoptosis by various stimuli. Cytochrome c is part of the apoptosome which consists of Apaf-1, caspase-9, and cytochrome c. Cytochrome c release and apoptosome activiation results in the activiation of caspase-9 and subsequently of the effector caspase cascade. More...
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