Caspase 1

Caspase 1, apoptosis-related cysteine peptidase

PDB rendering based on 1bmq.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols CASP1 ; ICE; IL1BC; P45
External IDs OMIM: 147678 MGI: 96544 HomoloGene: 133272 ChEMBL: 4801 GeneCards: CASP1 Gene
EC number 3.4.22.36
Orthologs
Species Human Mouse
Entrez 834 12362
Ensembl ENSG00000137752 ENSMUSG00000025888
UniProt P29466 P29452
RefSeq (mRNA) NM_001223 NM_009807
RefSeq (protein) NP_001214 NP_033937
Location (UCSC) Chr 11:
105.03 – 105.04 Mb
Chr 9:
5.3 – 5.31 Mb
PubMed search

Caspase 1/Interleukin-1 converting enzyme is an enzyme that proteolytically cleaves other proteins, such as the precursor forms of the inflammatory cytokines interleukin 1β and interleukin 18, into active mature peptides.[1][2][3] It plays a central role in cell immunity as an inflammatory response initiator. Once activated by an inflammasome complex, it initiates a two-fold inflammation response through the cleavage and activation of the two inflammatory cytokines interleukin 1β and interleukin 18 as well as the initiation of pyroptosis, a programmed lytic cell death pathway. The two inflammatory cytokines activated by Caspase 1 are secreted from the cell to act as a signals of pyroptosis to neighboring cells. [4]

Structure

Caspase 1 is produced as a zymogen that is 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 interacts with another CARD domain containing protein called PYCARD (or ASC) and is involved in inflammasome formation and activation of inflammatory processes.[3]

Function

Caspase 1 has been shown to induce cell necrosis or pyroptosis and may function in various developmental stages. Studies of a similar protein in mouse suggest a role in the pathogenesis of Huntington's disease. Alternative splicing of the gene results in five transcript variants encoding distinct isoforms.[5] Recent studies implicated caspase 1 in promoting CD4 T-cell death and inflammation by HIV, two signature events that fuel HIV disease progression to AIDS.[6][7]

Interactions

Caspase 1 has been shown to interact with NLRC4.[4][8][9]

See also

References

  1. Thornberry NA, Bull HG, Calaycay JR, Chapman KT, Howard AD, Kostura MJ, Miller DK, Molineaux SM, Weidner JR, Aunins J (1992). "A novel heterodimeric cysteine protease is required for interleukin-1 beta processing in monocytes". Nature 356 (6372): 768–74. doi:10.1038/356768a0. PMID 1574116.
  2. Cerretti DP, Kozlosky CJ, Mosley B, Nelson N, Van Ness K, Greenstreet TA, March CJ, Kronheim SR, Druck T, Cannizzaro LA (1992). "Molecular cloning of the interleukin-1 beta converting enzyme". Science 256 (5053): 97–100. doi:10.1126/science.1373520. PMID 1373520.
  3. 1 2 Mariathasan S, Newton K, Monack DM, Vucic D, French DM, Lee WP, Roose-Girma M, Erickson S, Dixit VM (2004). "Differential activation of the inflammasome by caspase-1 adaptors ASC and Ipaf". Nature 430 (6996): 213–8. doi:10.1038/nature02664. PMID 15190255.
  4. 1 2 Jorgensen, Ine; Miao, Edward A. (2015-05-01). "Pyroptotic cell death defends against intracellular pathogens". Immunological Reviews 265 (1): 130–142. doi:10.1111/imr.12287. ISSN 1600-065X. PMC 4400865. PMID 25879289.
  5. "Entrez Gene: CASP1 caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta, convertase)".
  6. Doitsh G, Galloway NL, Geng X, Yang Z, Monroe KM, Zepeda O, Hunt PW, Hatano H, Sowinski S, Muñoz-Arias I, Greene WC (2014). "Cell death by pyroptosis drives CD4 T-cell depletion in HIV-1 infection". Nature 505 (7484): 509–14. doi:10.1038/nature12940. PMC 4047036. PMID 24356306.
  7. Monroe KM, Yang Z, Johnson JR, Geng X, Doitsh G, Krogan NJ, Greene WC (2014). "IFI16 DNA sensor is required for death of lymphoid CD4 T cells abortively infected with HIV". Science 343 (6169): 428–32. doi:10.1126/science.1243640. PMC 3976200. PMID 24356113.
  8. Damiano JS, Oliveira V, Welsh K, Reed JC (2004). "Heterotypic interactions among NACHT domains: implications for regulation of innate immune responses". Biochem. J. 381 (Pt 1): 213–9. doi:10.1042/BJ20031506. PMC 1133779. PMID 15107016.
  9. Damiano JS, Stehlik C, Pio F, Godzik A, Reed JC (2001). "CLAN, a novel human CED-4-like gene". Genomics 75 (1-3): 77–83. doi:10.1006/geno.2001.6579. PMID 11472070.

External links

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