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OTUD7B inhibits NFkappaB. 13 / 16
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"In B cells, Otud7b suppresses the activation of noncanonical NF-kappaB signaling by deubiquitinating and stabilizing a negative regulator, TRAF3 201."
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"Moreover, OTUD7B negatively regulated NF-kappaB signaling pathway, which may be an effective target for antitumor therapy for HCC."
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"NF-kappaB is activated by Otud7b deficiency."
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"Moreover, Overexpression of OTUD7B or TNIP2 indeed antagonizes miR-1180-induced NF-kappaB activation, which further confirmed our conclusion that miR-1180-regulating OTUD7B (or TNIP2) - NF-kappaB- signaling regulation mediates HCC resistance (XREF_FIG and XREF_SUPPLEMENTARY)."
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"Cezanne is induced by TNF stimulation and inhibits NF-κB in a negative feedback loop ( xref )."
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"Loss of Cezanne increased transcriptional activity of NF-kappaB (Supplementary Fig S1E) as shown before XREF_BIBR, and also of p53 (Supplementary Fig S1F), suggesting that Cezanne can act as a positive and a negative regulator of transcription factors."
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"Consistently, the WT Otud7b, but not Otud7b CH, suppressed the activation of noncanonical NF-kappaB signaling (XREF_FIG)."
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"Previous studies have shown that OTUD7B inhibited NF-kappaB pathway by deconjugating K63-polyubiquitin chains from RIP-1 and TRAF6, suggesting that it may have roles in inhibition of cancer progression XREF_BIBR, XREF_BIBR."
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"Using RNA-sequencing and bioinformatics analysis followed by a luciferase reporter assay, we found that Otud7b downregulates NF-kappaB activity."
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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]."
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"Recent studies have suggested that OTUD7B (also known as Cezanne) negatively regulates signal induced noncanonical NF-kappaB pathway activation by deubiquitylating TRAF3."
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"Accumulation of NIK induces phosphorylation of the inhibitor of kappa-B kinase α (IKKα), leading to the ubiquitination and processing of p100. xref , xref , xref , xref The inactive precursor protein p100 undergoes proteasome-mediated processing to generate active protein p52, which binds to RelB and translocates to the nucleus. xref , xref , xref The deubiquitination of TRAF3 by Otud7b inhibits NF-κB activation by preventing TRAF3 proteolysis and NIK accumulation. xref Alternatively, the canonical pathway relies on ubiquitination of RIP1 kinase or TRAF6."
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"Thus although hypoxia primed cells for inflammatory activation it simultaneously induced Cezanne which impeded signalling to NF-kappaB by suppressing TRAF6 ubiquitination ."
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