CASP1
GeneName
CASP1
Summary
CASP1, also known as Caspase-1 or ICE, is a 45kDa cysteine protease that plays a pivotal role in the inflammatory response and apoptosis. It is primarily located in the cytoplasm and is part of various inflammasome complexes, including the AIM2, NLRP1, NLRP3, and IPAF inflammasome complexes. CASP1 is involved in the processing of cytokine precursors, such as interleukin-1 beta and interleukin-18, which are crucial for mediating inflammation. Its activity is regulated by CARD domain interactions and it also participates in the cellular response to pathogens, including bacteria and viruses, as well as in the response to lipopolysaccharide and type II interferon.
Importance
CASP1 is relevant to: - The study of inflammatory diseases due to its central role in the activation of pro-inflammatory cytokines - Research on pyroptosis, a form of programmed cell death associated with inflammation - Understanding the mechanisms of immune response to bacterial and viral infections - The development of therapeutic strategies targeting caspase-1 in conditions like sepsis and autoinflammatory syndromes
Top Products
For researchers investigating CASP1, we highly recommend the top-selling recombinant antibody, Anti-pro Caspase-1 + p10 + p12 antibody [EPR16883] (ab179515). This antibody has garnered significant attention in the research community, with 462 citations, underscoring its reliability and effectiveness. It has been validated for use in Western blotting (WB) and immunoprecipitation (IP), making it an excellent choice for those looking to explore the role of CASP1 in various biological processes. The recombinant nature of this antibody ensures batch-to-batch consistency, providing researchers with confidence in their experimental results.
Abcam Product Citation Summary
The data indicates that CASP1 is frequently studied in the context of inflammation and the NLRP3 inflammasome across various species, particularly in rats and mice. The use of Western blotting as a primary application highlights its importance in understanding the molecular mechanisms underlying conditions such as ischemia-reperfusion injury, pyroptosis, and neuropathic pain. Human studies also contribute to the understanding of CASP1's role in cancer and oxidative stress.
Abcam Product Citation Table
Function
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:15498465, PubMed:1574116, PubMed:26375003, PubMed:32051255, PubMed:37993714, PubMed:7876192, PubMed:9334240). 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:15326478, PubMed:15498465, PubMed:1574116, PubMed:32051255, PubMed:7876192). Cleaves a tetrapeptide after an Asp residue at position P1 (PubMed:15498465, PubMed:1574116, PubMed:7876192). 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).
Isoform Delta
Apoptosis inactive.
Isoform Epsilon
Apoptosis inactive.
Post-translational modifications
The two subunits are derived from the precursor sequence by an autocatalytic mechanism.
Ubiquitinated via 'Lys-11'-linked polyubiquitination. Deubiquitinated by USP8.
Cleavage in the interdomain linker region is required to induce pyroptosis.
Sequence Similarities
Belongs to the peptidase C14A family.
Tissue Specificity
Expressed in larger amounts in spleen and lung. Detected in liver, heart, small intestine, colon, thymus, prostate, skeletal muscle, peripheral blood leukocytes, kidney and testis. No expression in the brain.
Cellular localization
- Cytoplasm
- Cell membrane
Alternative names
IL1BC, IL1BCE, CASP1, Caspase-1, CASP-1, Interleukin-1 beta convertase, Interleukin-1 beta-converting enzyme, p45, IL-1BC, ICE, IL-1 beta-converting enzyme
Database links
swissprot:P29466 omim:147678 entrezGene:834
Other research areas
- Oncology