Anti-Caspase-8

Apoptosis, or programmed cell death, is a common property of all multicellular organisms. The current dogma of apoptosis suggests that the components of the core cell-death machinery are integral to cells and widely conserved across species. Caspases, a family of cysteinyl aspartate-specific proteases, are integral components of the cell death machinery (reviewed in Siegal, 2006, and Lavrik et al, 2005). They play a central role in the initiation and execution of apoptotic cell death and in inflammation. Caspases are typically divided into 3 major groups, depending on the structure of their prodomain and their function. Group 1: inflammatory caspases (caspases 1, 4, 5, 11, 12, 14). Group II: initiator of apoptosis caspases (caspases 2, 8, 9). Group II: effector caspases (caspases 3, 6, 7). Caspases are constitutively expressed in almost all cell types as inactive proenzymes (zymogens: enzyme precursors which require a biochemical change to become active enzymes) that are processed and activated in response to a variety of pro-apoptotic or inflammatory stimuli. The procaspases (32-56 kDa) contain four domains: an N-terminal prodomain (2-25 kDa), a large subunit (p20: 17-21 kDa), a small subunit (p10: 10-13 kDa) and a short linker region between the large and small subunits. Caspase activation involves proteolytic processing of the proenzyme at specific aspartate residues between the domains. This results in removal of the prodomain as well as the linker region and formation of a heterodimer containing one large and one small subunit (p20-p10). The active caspase is a tetramer composed of two heterodimers (p202-p102). Active caspases mediate cell death and inflammation through cleavage of particular cellular substrates that are involved in these processes.The antisera recognizes caspase-8 forms that contain the peptide immunogen sequence (PQPTFTLRKKLVFPSD). Protein function: 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. [The UniProt Consortium]