Caspase-8 is a caspase protein, encoded by the CASP8 gene. It most likely acts upon caspase-3. CASP8orthologs have been identified in numerous mammals for which complete genome data are available. These unique orthologs are also present in birds.
The CASP8 gene encodes a member of the cysteine-aspartic acidprotease (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.
A very rare genetic disorder of the immune system can also be caused by mutations in this gene. This disease, called CEDS, stands for “Caspase eight deficiency state.” It is characterized by splenomegaly and lymphadenopathy, in addition to recurrent sinopulmonary infections, recurrent mucocutaneous herpesvirus or other viral infections, and hypogammaglobulinemia.
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