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Details on Person Receptor-interacting serine/threonine-protein kinase 1 (RIPK...
| Class:Id | Summation:5433115 |
|---|---|
| _displayName | Receptor-interacting serine/threonine-protein kinase 1 (RIPK... |
| _timestamp | 2020-08-28 13:32:17 |
| created | [InstanceEdit:5433116] Shamovsky, V, 2014-05-12 |
| literatureReference | [LiteratureReference:451562] Activation of IKK by TNFalpha requires site-specific ubiquitination of RIP1 and polyubiquitin binding by NEMO [LiteratureReference:5357823] CLIPR-59 regulates TNF-?-induced apoptosis by controlling ubiquitination of RIP1 [LiteratureReference:5357741] CYLD deubiquitinates RIP1 in the TNF?-induced necrosome to facilitate kinase activation and programmed necrosis [LiteratureReference:5357775] Cleavage of the death domain kinase RIP by caspase-8 prompts TNF-induced apoptosis [LiteratureReference:5357755] Loss of caspase-8 expression in highly malignant human neuroblastoma cells correlates with resistance to tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis [LiteratureReference:5692297] Prevention of cellular suicide by cytomegaloviruses [LiteratureReference:2672185] Fas- and tumor necrosis factor-induced apoptosis is inhibited by the poxvirus crmA gene product [LiteratureReference:9687059] Cleavage of RIPK1 by caspase-8 is crucial for limiting apoptosis and necroptosis [LiteratureReference:9686991] RIP3 mediates the embryonic lethality of caspase-8-deficient mice [LiteratureReference:9687021] A dominant autoinflammatory disease caused by non-cleavable variants of RIPK1 [LiteratureReference:9687055] Mutations that prevent caspase cleavage of RIPK1 cause autoinflammatory disease [LiteratureReference:9687011] Death-domain dimerization-mediated activation of RIPK1 controls necroptosis and RIPK1-dependent apoptosis [LiteratureReference:9697730] RIPK1 can mediate apoptosis in addition to necroptosis during embryonic development [LiteratureReference:3465386] Mechanism of procaspase-8 activation by c-FLIPL [LiteratureReference:1267786] FLIP(L) induces caspase 8 activity in the absence of interdomain caspase 8 cleavage and alters substrate specificity |
| modified | [InstanceEdit:5660780] Shamovsky, V, 2015-01-06 [InstanceEdit:5692402] Shamovsky, Veronica, 2015-05-12 [InstanceEdit:5692499] Shamovsky, Veronica, 2015-05-12 [InstanceEdit:9687027] Shamovsky, Veronica, 2020-05-06 [InstanceEdit:9697786] Shamovsky, Veronica, 2020-08-20 [InstanceEdit:9698079] Shamovsky, Veronica, 2020-08-21 [InstanceEdit:9698104] Shamovsky, Veronica, 2020-08-22 [InstanceEdit:9698711] Shamovsky, Veronica, 2020-08-28 |
| text | Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) can be a part of cell death and survival signaling complexes. Whether RIPK1 functions in apoptosis, necroptosis or NFκB signaling is dependent on autocrine/paracrine signals, on the cellular context and tightly regulated by posttranslational modifications of RIP1 itself. The pro-survival function of RIPK1 is achieved by polyubiquitination which is required for recruitment of signaling molecules/complexes such as the IKK complex and the TAB2:TAK1 complex to mediate activation of NFκB signaling (Ea CK et al. 2006). CYLD-mediated deubiquitination of RIPK1 switches its pro-survival function to caspase-mediated pro-apoptotic signaling (Fujikura D et al. 2012; Moquin DM et al. 2013). Caspase-8 (CASP8) in human and rodent cells facilitates the cleavage of kinases RIPK1 and RIPK3 and prevents RIPK1/RIPK3-dependent necroptosis (Lin Y et al. 1999; Hopkins-Donaldson S et al. 2000; Newton K et al. 2019; Zhang X et al. 2019; Lalaoui N et al. 2020). CASP8-mediated cleavage of human RIPK1 after D324 (D325 in mice) separates the amino-terminal kinase domain from the carboxy-terminal part of the molecule preventing RIPK1 kinase activation through dimerization via the carboxy-terminal death domain and leads to the dissociation of the complex TRADD:TRAF2:RIP1:FADD:CASP8 (Lin Y et al. 1999; Meng H et al. 2018). The lack of CASP8 proteolytic activity in the presence of viral (e.g. CrmA and vICA) or pharmacological caspase inhibitors results in necroptosis induction via RIPK1 and RIPK3 (Tewari M & Dixit VM 1995; Fliss PM & Brune W 2012; Hopkins-Donaldson S et al. 2000). Cellular FLICE-like inhibitory protein (cFLIP), which is an NF-κB target gene, form heterodimer with procaspase-8 and inhibits activation of CASP8 within the the TRADD:TRAF2:RIP1:FADD:CASP8:FLIP complex (Yu JW et al. 2009; Pop C et al. 2011). The presence of cFLIP (long form) limits CASP8 to cleave CASP3/7 but allow cleavage of RIPK1 to cause the dissociation of the TRADD:TRAF2:RIP1:FADD:CASP8, thereby inhibiting both apoptosis and necroptosis (Boatright KM et al. 2004; Yu JW et al. 2009; Pop C et al. 2011; Feoktistova M et al. 2011). Mice that lack CASP8 or knock-in mice that express catalytically inactive CASP8 (C362A) die in a RIPK3- and MLKL-dependent manner during embryogenesis (Kaiser WJ et al. 2011; Newton K et al. 2019). Studies using mice that express RIPK1(D325A), in which the CASP8 cleavage site Asp325 had been mutated, further confirmed that cleavage of RIPK1 by CASP8 is a mechanism for dismantling death-inducing complexes for limiting aberrant cell death in response to stimuli (Newton K et al. 2019; Lalaoui N et al. 2020). Disrupted cleavage of RIPK1 variants with mutations at D324 by CASP8 in humans leads to an autoinflammatory response by promoting the activation of RIPK1 (Tao P et al. 2020; Lalaoui N et al. 2020). |
| (summation) | [BlackBoxEvent:5357828] RIPK1 is cleaved by CASP8 [Homo sapiens] |
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