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any of a group of proteases that mediate apoptosis

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/08/30 16:34:23」(JST)

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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]

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.^[4]

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.^[8]^[9]

References

^ 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.
^ 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.
^ Black RA, Kronheim SR, Merriam JE, March CJ, Hopp TP (1989). "A pre-aspartate-specific protease from human leukocytes that cleaves pro-interleukin-1 beta". J. Biol. Chem. 264 (10): 5323–6. PMID 2784432.
^ 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.
^ "Entrez Gene: CASP1 caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta, convertase)".
^ 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.
^ 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.
^ 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.
^ 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

The MEROPS online database for peptidases and their inhibitors: C14.001

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UpToDate Contents

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1. リウマチ性疾患におけるサイトカインネットワーク：治療の意味 cytokine networks in rheumatic diseases implications for therapy
2. 高IgD症候群：病態生理 hyperimmunoglobulin d syndrome pathophysiology
3. クリオピリン関連周期性発熱症候群および関連疾患 cryopyrin associated periodic syndromes and related disorders
4. サルモネラ胃腸炎の病因 pathogenesis of salmonella gastroenteritis
5. 周期性発熱症候群およびその他の自己炎症性疾患：概要 periodic fever syndromes and other autoinflammatory diseases an overview

English Journal

NLRP3 and ASC suppress lupus-like autoimmunity by driving the immunosuppressive effects of TGF-β receptor signalling.

Lech M1, Lorenz G1, Kulkarni OP1, Grosser MO1, Stigrot N1, Darisipudi MN1, Günthner R1, Wintergerst MW1, Anz D1, Susanti HE1, Anders HJ1.
Annals of the rheumatic diseases.Ann Rheum Dis.2015 Dec;74(12):2224-35. doi: 10.1136/annrheumdis-2014-205496. Epub 2014 Aug 18.
OBJECTIVES: The NLRP3/ASC inflammasome drives host defence and autoinflammatory disorders by activating caspase-1 to trigger the secretion of mature interleukin (IL)-1β/IL-18, but its potential role in autoimmunity is speculative.METHODS: We generated and phenotyped Nlrp3-deficient, Asc-deficient,
PMID 25135254

Identification of Interleukin-1β-Producing Monocytes That Are Susceptible to Pyronecrotic Cell Death in Patients With Neonatal-Onset Multisystem Inflammatory Disease.

Edwan JH1, Goldbach-Mansky R1, Colbert RA1.
Arthritis & rheumatology (Hoboken, N.J.).Arthritis Rheumatol.2015 Dec;67(12):3286-97. doi: 10.1002/art.39307.
OBJECTIVE: Spontaneous inflammatory responses initiated by NLRP3 mutations promote inflammasome-mediated interleukin-1β (IL-1β) processing and release and can induce rapid necrotic cell death. The cells that produce IL-1β in neonatal-onset multisystem inflammatory disease (NOMID) have not been cl
PMID 26245468

Japanese Journal

Aggregatibacter actinomycetemcomitansによるインフラマソームの活性化

阿部亜美,佐伯渉,長谷部晃,原博志,八若保孝,柴田健一郎
北海道歯学雑誌 35(2), 123-132, 2015-03
… ームは多様な生理活性をもつ炎症性サイトカインのひとつであるIL-1βの産生を制御する細胞内センサーである．近年，IL-1βが関与する炎症性疾患の多くがこの細胞内センサーの活性化と関連している可能性が示唆され，病態解明の手がかりとしてインフラマソームが注目されている．歯周炎はその病態形成にIL-1βが重要な役割を果たすが，歯周炎とインフラマソームとの関連を …
NAID 120005572448

Role of NLRP3 Inflammasomes in Hepatic Ischemia-reperfusion Injury

, ,
Inflammation and Regeneration 35(2), 061-068, 2015
… NLRP3 is an intracellular pattern recognition receptor and a component of NLRP3 inflammasomes that can induce caspase-1 activation, and regulate the processing of a potent inflammatory cytokine, interleukin-1β (IL-1β). …
NAID 130005063949

Related Pictures

Caspase 1 - Wikipedia, the free -Caspase-1 (p20) (mouse), mAb (Casper-1 caspase 1 - group picture, image by tag Caspase 1; Interleukin-1beta Converting pro-caspase-1; procaspase-1; protease Caspase 1 (Interleukin-1beta Converting

★リンクテーブル★

リンク元	「カスパーゼ」
関連記事	「caspase 1」

「カスパーゼ」

Caspase 1, apoptosis-related cysteine peptidase
	PDB rendering based on 1bmq.
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	1BMQ, 1IBC, 1ICE, 1RWK, 1RWM, 1RWN, 1RWO, 1RWP, 1RWV, 1RWW, 1RWX, 1SC1, 1SC3, 1SC4, 2FQQ, 2H48, 2H4W, 2H4Y, 2H51, 2H54, 2HBQ, 2HBR, 2HBY, 2HBZ, 3D6F, 3D6H, 3D6M, 3E4C, 3NS7
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
Gene ontology
Molecular function	• endopeptidase activity; • cysteine-type endopeptidase activity; • protein binding; • cysteine-type endopeptidase activator activity involved in apoptotic process; • cysteine-type endopeptidase activity involved in execution phase of apoptosis;
Cellular component	• extracellular region; • cytoplasm; • mitochondrion; • cytosol; • IPAF inflammasome complex; • NLRP1 inflammasome complex; • NLRP3 inflammasome complex; • AIM2 inflammasome complex;
Biological process	• response to hypoxia; • proteolysis; • apoptotic process; • activation of cysteine-type endopeptidase activity involved in apoptotic process; • signal transduction; • regulation of autophagy; • response to lipopolysaccharide; • interleukin-1 beta production; • response to ATP; • nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway; • positive regulation of I-kappaB kinase/NF-kappaB signaling; • innate immune response; • positive regulation of interleukin-1 alpha secretion; • positive regulation of interleukin-1 beta secretion; • regulation of inflammatory response; • mitochondrial depolarization; • membrane hyperpolarization; • pyroptosis; • cellular response to mechanical stimulus; • cellular response to organic substance; • execution phase of apoptosis; • programmed necrotic cell death; • toxin transport;
	Sources: Amigo / QuickGO
Orthologs
	v; t; e;

　　[★]

英: caspase
同: ICEファミリープロテアーゼ ICE family protease

ヒトICEプロテアーゼスーパーファミリー

Family	Caspase	Other Name	Recognition	Target (Truncation site)
caspase-1	caspase-1	ICE	WEHD	pro IL-1β (FEAD/G, YVHD/A), procaspase-3, procaspase-4
	caspase-4	ICErel-II, TX, ICH-2
	caspase-5	ICErel-III, TY
caspase-2	caspase-2	ICH-1	DEHD	PARP (DEVD/G)
caspase-2	caspase-9	ICE-LAP6, Mch6	LEHD	PARP, procaspase-3
caspase-3	caspase-3	CPP32, Yama	DEVD	PARP, SREBP (DEPD/S), U1snRNP (DGPD/G), lamin B, D4-GDI (DELD/S), DNA-PK (DEVD/N), DFF (DETD/S, DAVD/T), actin (ELPD/G) ?, PKCδ (DMQD/N) ?]]
	caspase-7	Mch3, ICE-LAP3, CMH-1	DEVD	PARP, procaspase-6
	caspase-6	Mch2	VEHD	lamin A (VEID/N)]]
	caspase-8	FLICE, MACH, Mch5	LETD	procaspase-3, Bid
	caspase-10	Mch4	LEXD
	caspase-11	Ich3

「caspase 1」

　　[★]

カスパーゼ1

関: IL-1 beta-converting enzyme、interleukin-1beta converting enzyme

[pmid1574116-1] 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.

[pmid1373520-2] 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.

[pmid2784432-3] Black RA, Kronheim SR, Merriam JE, March CJ, Hopp TP (1989). "A pre-aspartate-specific protease from human leukocytes that cleaves pro-interleukin-1 beta". J. Biol. Chem. 264 (10): 5323–6. PMID 2784432.

[pmid15190255-4] 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.

[5] "Entrez Gene: CASP1 caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta, convertase)".

[pmid24356306-6] 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.

[pmid24356113-7] 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.

[pmid15107016-8] 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.

[pmid11472070-9] 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.

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caspase-1