IndraLab

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OTULIN inhibits NFkappaB. 17 / 22
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"Nevertheless, the DUB OTULIN is identified to restrain the formation of M1 linked Ub chains on the bacterial coat, then sequester the recruitment of NEMO and ultimately inhibit NF-kappaB pathway."
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"It appears that OTULIN overexpression antagonizes NF-kappaB activation by removing Met1-polyUb, whereas OTULIN C129A acts as a high-affinity UBD that competes with other Met1 specific UBDs required for NF-kappaB signaling in a similar manner to the one recently reported for the overexpression of the NEMO UBAN domain."
23746843
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"As both CYLD and OTULIN negatively regulate the NF-kappaB signalling cascade, the impact of these deubiquitinases in different LUBAC dependent signalling cascades may be context dependent."
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"To directly address if OTULIN antagonizes NF-kappaB activation by disassembling Met1-Ub, we devised a system whereby a noncleavable (Gly76 --> Ser76; GS) Met1-Ub was docked to XIAP via an IAP binding [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
23806334
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"How the overexpression of OTULIN attenuated NF-kappaB activation at the ubiquitination level was not explored in the current study."
29544517
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"Formation of the secondary, receptor-free cytoplasmic complex II is largely dependent on the activity of DUBs, specifically cylindromatosis (CYLD), A20 (also known as TNFAIP3) and ubiquitin thioesterase OTULIN, which destabilize complex I, abrogate NF-kappaB activation and release RIPK1 from complex I, which then forms the cytosolic complex II XREF_BIBR, XREF_BIBR."
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"CYLD and OTULIN were not inhibiting NF-kappaB activity per se because the DUBs did not appreciably inhibit NF-kappaB activity induced by an engineered non cleavable Met1-Ub4 protein targeted to inactive XIAP."
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"Increased OTULIN expression was required for EA to inhibit the NF-kappaB signalling pathway in focal cerebral ischaemia and reperfusion rats."
33836646
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"OTULIN is upregulated in a PRRSV infection model and interacts with the PRRSV non-structural protein 11 ( Nsp11 ) to decrease Ub levels on NEMO and to block NF-kappaB activation and IFN-regulatory transcription factor 3 ( IRF3 ) - mediated type-I IFN production [ 22 ] ."
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"Overexpression of OTULIN inhibits TNF-alpha-induced NF-kappaB signaling by preventing the association of NEMO with polyubiquitinated RIP1 (Fiil et al., 2013; Keusekotten et al., 2013)."
25175772
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"Loss of OTULIN expression in mouse hepatocytes increases cellular Met1 Ub levels, decreases LUBAC levels and does not induce NF-kappaB hyper-signaling, but sensitizes to apoptosis [XREF_BIBR, XREF_BIBR], in line with previous reports [XREF_BIBR, XREF_BIBR]."
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"For example, the deubiquitinases Gumby (OTULIN), OTUD7b, and TNFAIP3 (A20) in the OUT family were shown to negatively regulate NFkappaB activation through different mechanisms in different biological contexts [XREF_BIBR - XREF_BIBR]."
29202128
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"Moreover, OTULIN overexpression significantly attenuated NF-kappaB activity in the ischemic cortex, as determined by the inhibition of IkappaBalpha degradation and phosphorylation along with reduced nuclear translocation of p65, which manifested as less p65 in the nucleus and more p65 in the cytoplasm."
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"Ectopic expression of OTULIN in HEK293 and HeLa cells inhibits LUBAC dependent NF-kappaB signaling, suggesting that OTULIN is a negative regulator of this signaling pathway 18, 20."
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"To further investigate whether enhanced OTULIN was required for EA to inhibit the NF-kappaB signalling pathway, OTULIN, p-IkappaBalpha, IkappaBalpha, cytoplasm-p65 and nucleus-p65 proteins from brain tissues in the ischaemic penumbra of the cerebral cortex were detected 24h after reperfusion."
33836646
eidos
"TNFalpha-mediated NF-kappaB activation and gene transcription decrease upon ectopic expression of OTULIN , while OTULIN knockdown enhances NF-kappaB activation and LUBAC auto-ubiquitination [ 16 ] ."
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"In comparison, OTULIN inhibits TNFα-mediated NF-κB by ∼50%, which correlates with effects observed by LUBAC downregulation ( xref ; xref ) ( xref A)."
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