Aliases for CASP8 Gene
External Ids for CASP8 Gene
This gene encodes a member of the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes composed of a prodomain, a large protease subunit, and a small protease subunit. Activation of caspases requires proteolytic processing at conserved internal aspartic residues to generate a heterodimeric enzyme consisting of the large and small subunits. This protein is involved in the programmed cell death induced by Fas and various apoptotic stimuli. The N-terminal FADD-like death effector domain of this protein suggests that it may interact with Fas-interacting protein FADD. This protein was detected in the insoluble fraction of the affected brain region from Huntington disease patients but not in those from normal controls, which implicated the role in neurodegenerative diseases. Many alternatively spliced transcript variants encoding different isoforms have been described, although not all variants have had their full-length sequences determined. [provided by RefSeq, Jul 2008]
GeneCards Summary for CASP8 Gene
CASP8 (Caspase 8, Apoptosis-Related Cysteine Peptidase) is a Protein Coding gene. Diseases associated with CASP8 include autoimmune lymphoproliferative syndrome with recurrent viral infections and autoimmune lymphoproliferative syndrome, type iib. Among its related pathways are Pathways in cancer and ERK Signaling. GO annotations related to this gene include cysteine-type peptidase activity and cysteine-type endopeptidase activity. An important paralog of this gene is CASP1.
UniProtKB/Swiss-Prot for CASP8 Gene
Most upstream protease of the activation cascade of caspases responsible for the TNFRSF6/FAS mediated and TNFRSF1A induced cell death. Binding to the adapter molecule FADD recruits it to either receptor. The resulting aggregate called death-inducing signaling complex (DISC) performs CASP8 proteolytic activation. The active dimeric enzyme is then liberated from the DISC and free to activate downstream apoptotic proteases. Proteolytic fragments of the N-terminal propeptide (termed CAP3, CAP5 and CAP6) are likely retained in the DISC. Cleaves and activates CASP3, CASP4, CASP6, CASP7, CASP9 and CASP10. May participate in the GZMB apoptotic pathways. Cleaves ADPRT. Hydrolyzes the small-molecule substrate, Ac-Asp-Glu-Val-Asp- -AMC. Likely target for the cowpox virus CRMA death inhibitory protein. Isoform 5, isoform 6, isoform 7 and isoform 8 lack the catalytic site and may interfere with the pro-apoptotic activity of the complex.
Caspases (short for cysteinyl aspartate proteases) are involved in the signal transduction pathways of apoptosis, necrosis and inflammation. These enzymes can be divided into two major classes - initiators and effectors. The initiator isoforms (caspases-1,-4,-5,-8,-9,-10,-11,-12) are activated by, and interact with, upstream adaptor molecules through protein-protein interaction domains known as CARD and DED. Effector caspases (-3,-6,-7) are responsible for cleaving downstream substrates and are sometimes referred to as the executioner caspases. More than 400 caspase substrates have so far been identified (see The Caspase Substrate Database). Initiator caspases, such as caspase 8, may be directly activated by death receptors such as FasR. Caspases can also be found intracellularly as part of large multiprotein complexes. For example, caspase 9 is recruited to the apoptosome formed during apoptosis, whilst caspases-1 and 5 can form part of the inflammasome, a key part of cytokine processing during inflammation. Caspases are regulated by inhibitors of apoptosis and by dominant negative isoforms. They have been implicated in the pathogenesis of many disorders including stroke, Alzheimers disease, myocardial infarction, cancer, and inflammatory disease.