CASP7
Description
The CASP7 (caspase 7) is a protein-coding gene located on chromosome 10.
Caspase-7, apoptosis-related cysteine peptidase, also known as CASP7, is a human protein encoded by the CASP7 gene. CASP7 orthologs have been identified in nearly all mammals for which complete genome data are available. Unique orthologs are also present in birds, lizards, lissamphibians, and teleosts.
== Function == Caspase-7 is a member of the caspase (cysteine aspartate protease) family of proteins, and has been shown to be an executioner protein of apoptosis. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes that undergo proteolytic processing by upstream caspases (caspase-8, -9) at conserved aspartic residues to produce two subunits, large and small, that dimerize to form the active enzyme in the form of a heterotetramer. The precursor of this caspase is cleaved by caspase 3, caspase 10, and caspase 9. It is activated upon cell death stimuli and induces apoptosis. Alternative splicing results in four transcript variants, encoding three distinct isoforms.
CASP7, also known as caspase-7, is a thiol protease involved in various programmed cell death pathways, including apoptosis, pyroptosis, and granzyme-mediated programmed cell death. It achieves this by proteolytically cleaving target proteins. CASP7 exhibits a strong preference for Asp-Glu-Val-Asp (DEVD) consensus sequences, but can also interact with alternative non-canonical sequences. The specific role of CASP7 in different cell death pathways is likely determined by upstream proteases responsible for its activation. As an effector caspase, CASP7 participates in the execution phase of apoptosis. Following activation by initiator caspases (CASP8, CASP9, and/or CASP10), it mediates apoptosis by cleaving proteins such as CLSPN, PARP1, PTGES3, and YY1. Although a minor executioner caspase compared to CASP3, CASP7 cleaves a specific set of target proteins. In response to bacterial infection, CASP7 plays a critical role in regulating the inflammatory response by cleaving and activating the sphingomyelin phosphodiesterase SMPD1 in the extracellular milieu, thereby promoting membrane repair. CASP7 regulates pyroptosis in intestinal epithelial cells. Cleaved and activated by CASP1 upon S.typhimurium infection, CASP7 is secreted into the extracellular milieu where it activates SMPD1, generating ceramides that repair membranes and counteract the effects of gasdermin-D (GSDMD) pores. Similarly, CASP7 regulates granzyme-mediated programmed cell death in hepatocytes. Cleaved and activated by granzyme B (GZMB) in response to bacterial infection, CASP7 is secreted extracellularly, activating SMPD1 and generating ceramides that repair membranes and counter the action of perforin (PRF1) pores. Following inflammasome activation and cleavage by CASP1, CASP7 processes and inactivates PARP1, alleviating its transcription repressor activity. CASP7 inhibits type I interferon production during virus-induced apoptosis by cleaving antiviral proteins CGAS, IRF3, and MAVS, preventing excessive cytokine production. Additionally, CASP7 cleaves and activates sterol regulatory element binding proteins (SREBPs) and cleaves phospholipid scramblase proteins XKR4, XKR8, and XKR9. During infection, CASP7 cleaves the Kaposi sarcoma-associated herpesvirus protein ORF57, preventing the expression of viral lytic genes.
CASP7 is also known as CASP-7, CMH-1, ICE-LAP3, LICE2, MCH3.
