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Details on Person Severe acute respiratory syndrome-associated coronavirus typ...
| Class:Id | Summation:9686332 |
|---|---|
| _displayName | Severe acute respiratory syndrome-associated coronavirus typ... |
| _timestamp | 2021-01-07 14:40:36 |
| created | [InstanceEdit:9686330] Shamovsky, Veronica, 2020-04-30 |
| literatureReference | [LiteratureReference:9686326] SARS-Coronavirus Open Reading Frame-3a drives multimodal necrotic cell death [LiteratureReference:5620996] Phosphorylation-driven assembly of the RIP1-RIP3 complex regulates programmed necrosis and virus-induced inflammation [LiteratureReference:5218869] The RIP1/RIP3 necrosome forms a functional amyloid signaling complex required for programmed necrosis [LiteratureReference:5364112] Toll-like receptor 3-mediated necrosis via TRIF, RIP3, and MLKL [LiteratureReference:5620989] Mixed lineage kinase domain-like protein MLKL causes necrotic membrane disruption upon phosphorylation by RIP3 [LiteratureReference:9686464] RIPK1 counteracts ZBP1-mediated necroptosis to inhibit inflammation [LiteratureReference:5218888] Mixed lineage kinase domain-like protein mediates necrosis signaling downstream of RIP3 kinase [LiteratureReference:5364089] The pseudokinase MLKL mediates necroptosis via a molecular switch mechanism |
| modified | [InstanceEdit:9686457] Shamovsky, Veronica, 2020-05-01 [InstanceEdit:9689635] Shamovsky, Veronica, 2020-05-21 [InstanceEdit:9696115] Shamovsky, Veronica, 2020-07-17 [InstanceEdit:9698870] Shamovsky, Veronica, 2020-08-30 [InstanceEdit:9706017] Shamovsky, Veronica, 2020-11-04 [InstanceEdit:9711028] Shamovsky, Veronica, 2021-01-07 |
| text | Severe acute respiratory syndrome-associated coronavirus type 1 (SARS-CoV-1) 3a protein was shown to interact with receptor interacting protein kinase 3 (RIPK3) by immunoprecipitation analysis upon co-expression of viral 3a and RIPK3 in human embryonic kidney 293 (HEK293) cells (Yue Y et al. 2018). Mapping of the interaction between RIPK3 and 3a showed that the kinase domain of RIPK3 (1–326) interacted with SARS-CoV-1 3a, but that the RIP homotypic interaction motif (RHIM) containing C-terminus (327–518) interacted very weakly. Time-lapse confocal microscopy using Cherry-tagged RIP3 in HeLa cells expressing SARS-CoV-1 3a-GFP showed that expression of RIPK3 drives cell death in the presence of SARS 3a. Further, RIPK3-induced oligomerization of SARS-CoV-1 3a (studied with the oligomerization-deficient viral 3a-flag C133A mutant) helped drive necrotic cell death in RIPK3-expressing HEK293, HeLa and 5-Aza-2′-deoxycytidine (5-AD)-treated human alveolar epithelial A549 cells (Yue Y et al. 2018). The A549 cell line is resistant to the traditional necroptotic stimuli, but treatment with hypomethylating agents such as 5-AD induced RIPK3 expression (Yue Y et al. 2018). The results of the study suggest that SARS-Cov-1 3a does not induce cell death in the absence of RIPK3, but induces significant oligomerization-dependent death in the presence of endogenous RIPK3. (Yue Y et al. 2018). During tumor necrosis factor (TNF)-induced necroptosis, RIPK3 and RIPK1 associate with each other through their RHIM domains into heteromeric RIPK1:RIPK3 complexes that further polymerize into filamentous β-amyloid structures promoting the activation of RIPK3 kinase (Cho Y et al. 2009; Li J et al. 2012). Functionally active RIPK3 activates mixed-lineage kinase domain-like pseudokinase (MLKL), the membrane-disrupting effector of programmed necrosis (Sun L et al. 2012; Murphy JM et al. 2013; Wang H et al. 2014). Other RHIM-containing proteins, such as the TLR3/TLR4 adaptor TRIF (also known as TICAM1) and the DNA sensor DAI/ZBP can form the necroptotic signaling platforms to support activation of RIPK3 and its interaction with MLKL (Kaiser W et al. 2013; Lin J et al. 2016). This Reactome event shows a scaffolding role of RIPK3 bound to RIPK1 in supporting the formation of SARS-CoV-1 3a oligomers. |
| (summation) | [Reaction:9686345] SARS-CoV-1 3a binds RIPK1:RIPK3 oligomer [Homo sapiens] |
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