Caspase 8 (CASP8) Antibody – Rabbit Polyclonal

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]

CASP8: 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. Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a 18 kDa (p18) and a 10 kDa (p10) subunit. Interacts with FADD, CFLAR and PEA15. Isoform 9 interacts at the endoplasmic reticulum with a complex containing BCAP31, BAP29, BCL2 and/or BCL2L1. Interacts with TNFAIP8L2. Interacts with human cytomegalovirus/HHV-5 protein vICA/UL36; this interaction inhibits CASP8 activation. Isoform 1, isoform 5 and isoform 7 are expressed in a wide variety of tissues. Highest expression in peripheral blood leukocytes, spleen, thymus and liver. Barely detectable in brain, testis and skeletal muscle. Belongs to the peptidase C14A family. 9 isoforms of the human protein are produced by alternative splicing.

Protein type: Apoptosis; EC 3.4.22.61; Protease

Chromosomal Location of Human Ortholog: 2q33.1

Cellular Component: CD95 death-inducing signaling complex; cell body; cytoskeleton; cytosol; membrane raft; mitochondrial outer membrane; mitochondrion; neuron projection; nucleoplasm

Molecular Function: cysteine-type endopeptidase activity; cysteine-type peptidase activity; death receptor binding; identical protein binding; peptidase activity; protein binding; protein complex binding; tumor necrosis factor receptor binding; ubiquitin protein ligase binding

Biological Process: activation of cysteine-type endopeptidase activity involved in apoptotic process; activation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway; apoptosis; B cell activation; cell surface receptor signaling pathway; cellular response to organic cyclic compound; death-inducing signaling complex assembly; macrophage differentiation; natural killer cell activation; negative regulation of extrinsic apoptotic signaling pathway via death domain receptors; negative regulation of I-kappaB kinase/NF-kappaB signaling; nucleotide-binding oligomerization domain containing signaling pathway; positive regulation of I-kappaB kinase/NF-kappaB signaling; positive regulation of macrophage differentiation; positive regulation of neuron death; positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway; positive regulation of proteolysis; proteolysis; proteolysis involved in cellular protein catabolic process; regulation of extrinsic apoptotic signaling pathway via death domain receptors; regulation of tumor necrosis factor-mediated signaling pathway; response to antibiotic; response to cobalt ion; response to cold; response to estradiol; response to ethanol; response to lipopolysaccharide; response to tumor necrosis factor; T cell activation; toll-like receptor 3 signaling pathway; TRAIL-activated apoptotic signaling pathway

Disease: Breast Cancer; Caspase 8 Deficiency; Hepatocellular Carcinoma; Lung Cancer