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Details on Person During infection, viruses can trigger the assembly of the NO...
| Class:Id | Summation:9712403 |
|---|---|
| _displayName | During infection, viruses can trigger the assembly of the NO... |
| _timestamp | 2021-07-13 03:16:02 |
| created | [InstanceEdit:9712406] Shamovsky, Veronica, 2021-01-19 |
| literatureReference | [LiteratureReference:874043] The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta [LiteratureReference:844443] The inflammasomes [LiteratureReference:879193] A unified model for apical caspase activation [LiteratureReference:9712397] Caspase-1 self-cleavage is an intrinsic mechanism to terminate inflammasome activity [LiteratureReference:9710021] Structural Mechanism for GSDMD Targeting by Autoprocessed Caspases in Pyroptosis [LiteratureReference:9712409] Crystal structure of procaspase-1 zymogen domain reveals insight into inflammatory caspase autoactivation [LiteratureReference:9712411] Substrate and inhibitor-induced dimerization and cooperativity in caspase-1 but not caspase-3 [LiteratureReference:9708068] The NLRP3 inflammasome: molecular activation and regulation to therapeutics [LiteratureReference:9708079] Mechanism and Regulation of NLRP3 Inflammasome Activation [LiteratureReference:9708040] Recent advances in the mechanisms of NLRP3 inflammasome activation and its inhibitors [LiteratureReference:9708036] Inflammasome activation and regulation: toward a better understanding of complex mechanisms [LiteratureReference:9708063] The mitochondrial antiviral protein MAVS associates with NLRP3 and regulates its inflammasome activity [LiteratureReference:9708085] The adaptor MAVS promotes NLRP3 mitochondrial localization and inflammasome activation [LiteratureReference:9685266] MAVS Promotes Inflammasome Activation by Targeting ASC for K63-Linked Ubiquitination via the E3 Ligase TRAF3 [LiteratureReference:9712423] Cutting Edge: Mitochondrial Assembly of the NLRP3 Inflammasome Complex Is Initiated at Priming |
| modified | [InstanceEdit:9712426] Shamovsky, Veronica, 2021-01-19 [InstanceEdit:9712432] Shamovsky, Veronica, 2021-01-19 [InstanceEdit:9735691] Shamovsky, Veronica, 2021-06-29 [InstanceEdit:9736587] Shamovsky, Veronica, 2021-07-13 |
| text | During infection, viruses can trigger the assembly of the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome complex on the mitochondrial surface (Elliott EI et al. 2018; Park S et al. 2013). The mitochondrial antiviral protein (MAVS) was shown to bind NLRP3 promoting the NLRP3 inflammasome activation at mitochondria (Subramanian N et al. 2013; Park S et al. 2013; Guan K et al. 2015). Infection of human THP-1 cells with Sendai virus (SV) led to MAVS-mediated NLRP3-dependent activation of caspase-1 (CASP1) (Park S et al. 2013). CASP1 exists as an inactive zymogen (CASP1(1-404)), which is recruited to the inflammasome complex through the C-terminal caspase recruitment domain (CARD) of PYCARD (ASC) (reviewed in Martinon F et al. 2002; Schroder K & Tschopp J 2010). Dimerization of zymogens is considered to be essential for the activation of caspases (Boatright KM et al. 2003; Boucher D et al. 2018; Wang K et al. 2020). PYCARD oligomerization promotes clustering and proximity-mediated self-cleavage of CASP1(1-404). It is assumed that the enzymatically active CASP1 in mammalian cells is a heterotetramer, which is composed of two p20 (CASP1(120-297)) and two p10 (CASP1(317-404)) subunits (a homodimer of p20:p10 dimers) (Elliott JM et al. 2009; Datta D et al. 2013). Once activated, p20:p10 species of CASP1 are released from the inflammasome complex for subsequent substrate cleavage. However, CASP1 can undergo self-cleavage at multiple sites within the two linker domains to potentially generate diverse dimeric CASP1 species such as a transient proteolytically active p33:p10 (CASP1(1-297):CASP1(317-404)) (Boucher D et al. 2018). The complex of inflammasome with p33:p10 heterodimer of CASP1 is thought to function as a holoenzyme that directs the location of CASP1 protease activity, while generation and release of p20:p10 species leads to the inactivation of CASP1 (Boucher D et al. 2018). The exact mechanism of the CASP1 activation requires further clarification. This Reactome event shows autoprocessing of the dimeric CASP1(1-404) zymogen within the NLRP3 inflammasome bound to the mitochondrial MAVS. The cleavage releases the catalytic domain, which is composed of two covalently linked subunits, CASP1(120-297) and CASP1(317-404). The active form of CASP1 is shown as a homodimer of two catalytic domains, 2x(CASP1(120-297):CASP1(317-404)). Once activated, CASP1 cleaves pro‐inflammatory cytokines pro-interleukin (IL)‐1β, pro-IL‐18, and the pyroptotic cell death effector gasdermin D (GSDMD) (reviewed in He Y et al. 2016; Yang Y et al. 2019; Zheng D et al. 2020; Swanson KV et al. 2019). |
| (summation) | [BlackBoxEvent:9712407] CASP1 is activated by autoproteolysis [Homo sapiens] |
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