CASP3
Description
The CASP3 (caspase 3) is a protein-coding gene located on chromosome 4.
Caspase-3 is a caspase protein that interacts with caspase-8 and caspase-9. It is encoded by the CASP3 gene. CASP3 orthologs have been identified in numerous mammals for which complete genome data are available. Unique orthologs are also present in birds, lizards, lissamphibians, and teleosts. The CASP3 protein is 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 that undergo proteolytic processing at conserved aspartic residues to produce two subunits, large and small, that dimerize to form the active enzyme. This protein cleaves and activates caspases 6 and 7; and the protein itself is processed and activated by caspases 8, 9, and 10. It is the predominant caspase involved in the cleavage of amyloid-beta 4A precursor protein, which is associated with neuronal death in Alzheimer's disease. Alternative splicing of this gene results in two transcript variants that encode the same protein.
CASP3 is a thiol protease that functions as a key effector caspase in the execution phase of apoptosis. After being cleaved and activated by initiator caspases (CASP8, CASP9, and/or CASP10), it mediates the execution of apoptosis by catalyzing the cleavage of numerous proteins. During the initiation of apoptosis, CASP3 proteolytically cleaves poly(ADP-ribose) polymerase (PARP1) at a '216-Asp-|-Gly-217' bond. CASP3 cleaves and activates sterol regulatory element binding proteins (SREBPs) between the basic helix-loop-helix leucine zipper domain and the membrane attachment domain. CASP3 cleaves and activates caspase-6, -7, and -9 (CASP6, CASP7, and CASP9, respectively). CASP3 cleaves and inactivates interleukin-18 (IL18). CASP3 is involved in the cleavage of huntingtin. CASP3 triggers cell adhesion in sympathetic neurons through RET cleavage. CASP3 cleaves and inhibits serine/threonine-protein kinase AKT1 in response to oxidative stress. CASP3 acts as an inhibitor of type I interferon production during virus-induced apoptosis by mediating the cleavage of antiviral proteins CGAS, IRF3, and MAVS, preventing cytokine overproduction. CASP3 is also involved in pyroptosis by mediating the cleavage and activation of gasdermin-E (GSDME). CASP3 cleaves XRCC4 and phospholipid scramblase proteins XKR4, XKR8, and XKR9, leading to the promotion of phosphatidylserine exposure on the apoptotic cell surface.
CASP3 is also known as CPP32, CPP32B, SCA-1.
