CASP1
Description
The CASP1 (caspase 1) is a protein-coding gene located on chromosome 11.
Caspase-1/Interleukin-1 converting enzyme (ICE) is an evolutionarily conserved enzyme that proteolytically cleaves other proteins, such as the precursors of the inflammatory cytokines interleukin 1β and interleukin 18 as well as the pyroptosis inducer Gasdermin D, into active mature peptides. It plays a central role in cell immunity as an inflammatory response initiator. Once activated through formation of an inflammasome complex, it initiates a proinflammatory response through the cleavage and thus activation of the two inflammatory cytokines, interleukin 1β (IL-1β) and interleukin 18 (IL-18) as well as pyroptosis, a programmed lytic cell death pathway, through cleavage of Gasdermin D. The two inflammatory cytokines activated by Caspase-1 are excreted from the cell to further induce the inflammatory response in neighboring cells.
== Cellular expression == Caspase-1 is evolutionarily conserved in many eukaryotes of the Kingdom Animalia. Due to its role in the inflammatory immune response, it is highly expressed in the immune organs such as the liver, kidney, spleen, and blood (neutrophils). Following infection, the inflammatory response increases expression of Caspase-1, by a positive feedback mechanism that amplifies the response.
== Structure == Caspase-1 is produced as a zymogen that can then be cleaved into 20 kDa (p20) and 10 kDa (p10) subunits that become part of the active enzyme. Active Caspase 1 contains two heterodimers of p20 and p10. It contains a catalytic domain with an active site that spans both the p20 and p10 subunits, as well as a noncatalytic Caspase Activation and Recruitment Domain (CARD) . It interacts with other CARD containing proteins such as Apoptosis-Associated Speck-like Protein Containing a CARD (ASC) and Nod-Like Receptor (NLR) Family CARD Domain-Containing Protein 4 (NLRC4) through CARD-CARD interactions in the formation of inflammasomes.
Thiol protease involved in a variety of inflammatory processes by proteolytically cleaving other proteins, such as the precursors of the inflammatory cytokines interleukin-1 beta (IL1B) and interleukin 18 (IL18) as well as the pyroptosis inducer Gasdermin-D (GSDMD), into active mature peptides (PubMed:15326478, PubMed:1574116, PubMed:7876192, PubMed:15498465, PubMed:9334240, PubMed:26375003, PubMed:32051255, PubMed:37993714). Plays a key role in cell immunity as an inflammatory response initiator: once activated through formation of an inflammasome complex, it initiates a pro-inflammatory response through the cleavage of the two inflammatory cytokines IL1B and IL18, releasing the mature cytokines which are involved in a variety of inflammatory processes (PubMed:1574116, PubMed:7876192, PubMed:15498465, PubMed:15326478, PubMed:32051255). Cleaves a tetrapeptide after an Asp residue at position P1 (PubMed:1574116, PubMed:7876192, PubMed:15498465). Also initiates pyroptosis, a programmed lytic cell death pathway, through cleavage of GSDMD (PubMed:26375003). In contrast to cleavage of interleukin IL1B, recognition and cleavage of GSDMD is not strictly dependent on the consensus cleavage site but depends on an exosite interface on CASP1 that recognizes and binds the Gasdermin-D, C-terminal (GSDMD-CT) part (PubMed:32051255, PubMed:32109412, PubMed:32553275). Cleaves and activates CASP7 in response to bacterial infection, promoting plasma membrane repair (PubMed:22464733). Upon inflammasome activation, during DNA virus infection but not RNA virus challenge, controls antiviral immunity through the cleavage of CGAS, rendering it inactive (PubMed:28314590). In apoptotic cells, cleaves SPHK2 which is released from cells and remains enzymatically active extracellularly (PubMed:20197547). {ECO:0000269|PubMed:15326478, ECO:0000269|PubMed:15498465, ECO:0000269|PubMed:1574116, ECO:0000269|PubMed:20197547, ECO:0000269|PubMed:22464733, ECO:0000269|PubMed:26375003, ECO:0000269|PubMed:28314590, ECO:0000269|PubMed:32051255, ECO:0000269|PubMed:32109412, ECO:0000269|PubMed:32553275, ECO:0000269|PubMed:37993714, ECO:0000269|PubMed:7876192, ECO:0000269|PubMed:9334240}
CASP1 is also known as ICE, IL1BC, P45.
