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Details on Person Genome-wide siRNA screening identified spermatogenesis-assoc...
| Class:Id | Summation:9796692 |
|---|---|
| _displayName | Genome-wide siRNA screening identified spermatogenesis-assoc... |
| _timestamp | 2022-08-12 11:27:20 |
| created | [InstanceEdit:9796688] Shamovsky, Veronica, 2022-08-12 |
| literatureReference | [LiteratureReference:9796695] SPATA2 regulates the activation of RIPK1 by modulating linear ubiquitination [LiteratureReference:9796372] SPATA2 Links CYLD to LUBAC, Activates CYLD, and Controls LUBAC Signaling [LiteratureReference:9796386] SPATA2-Mediated Binding of CYLD to HOIP Enables CYLD Recruitment to Signaling Complexes [LiteratureReference:9796402] SPATA2 links CYLD to the TNF-α receptor signaling complex and modulates the receptor signaling outcomes [LiteratureReference:9796345] SPATA2 promotes CYLD activity and regulates TNF-induced NF-κB signaling and cell death [LiteratureReference:9796689] SPATA2: more than a missing link [LiteratureReference:9796693] Identification of a molecular signaling network that regulates a cellular necrotic cell death pathway |
| modified | [InstanceEdit:9796719] Shamovsky, Veronica, 2022-08-12 |
| text | Genome-wide siRNA screening identified spermatogenesis-associated protein 2 (SPATA2 ) as a gene involved in mediating necroptosis (Hitomi J et al. 2008). Under steady-state conditions, SPATA2 was shown to interact with deubiquitinating enzyme CYLD and HOIP, the catalytic subunit of the linear ubiquitin chain assembly complex (LUBAC) (Wagner SA et al. 2016; Elliott PR et al. 2016; reviewed in Schlicher L et al. 2017). Structural and biochemical studies revealed that the N-terminal PNGase/UBA or UBX (PUB) domain of SPATA2 interacts with the USP domain of CYLD, whereas the C-terminal PUB-interacting motif (PIM) of SPATA2 binds the PUB domain of HOIP (reviewed in Schlicher L et al. 2017; Elliott PR et al. 2016; Kupka S et al. 2016; Schlicher L et al. 2016). In TNFα-stimulated human and mouse cells, CYLD:SPATA2:LUBAC is rapidly recruited into the TNFR1 signaling complex (Wagner SA et al. 2016; Elliott PR et al. 2016; Kupka S et al. 2016; Schlicher L et al. 2016; Wei R et al. 2017; reviewed in Schlicher L et al. 2017). Knockdown of SPATA2 selectively abolished CYLD interaction with the TNFR1 complex, without abolishing binding of LUBAC components (Wagner SA et al. 2016). Within the TNFR1 signaling complex, SPATA2 promotes the deubiquitinase activity of CYLD resulting in CYLD-mediated removal of Met1- and K63-linked polyubiquitin chains from specific substrates such as RIPK1 (Wei R et al. 2017). SPATA2 deficiency increased the Met1-linked ubiquitination of RIPK1, which resulted in inhibition of RIPK1 kinase activity and RIPK1-mediated cell death in mouse cells (Wei R et al. 2017). SPATA2 deficiency promoted the production of proinflammatory cytokines in TNFα-treated mice in vivo (Wei R et al. 2017). Further, SPATA2 deficiency protected against TNF-induced cell death in human and mouse cells (Wagner SA et al. 2016; Kupka S et al. 2016; Schlicher L et al. 2016; Wei R et al. 2017). These data suggest that SPATA2 regulates inflammatory signaling and cell death program via linking CYLD and LUBAC to limit LUBAC-mediated Met1-Ub. The Reactome event shows the formation of the CYLD:SPATA2:LUBAC complex. The stoichiometry of the trimeric CYLD:SPATA2:LUBAC complex is shown as 2:2:2 (Elliott PR et al. 2016). |
| (summation) | [Reaction:9796691] SPATA2 links CYLD to LUBAC [Homo sapiens] |
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No pathways have been reviewed or authored by Genome-wide siRNA screening identified spermatogenesis-assoc... (9796692)
