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OTUB1 inhibits Ubiquitin. 29 / 35
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"With in vivo and in vitro ubiquitination assays, OTUB1 is shown to block ubiquitin transfer to YTHDF2 independent of its deubiquitinase activity."
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"IL-15 mediates membrane recruitment of Otub1, which inhibits ubiquitin-dependent activation of AKT, a pivotal kinase for T cell activation and metabolism."
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"Further, UbcH5 in turn mediates Otub1 monoubiquitination and this monoubiquitination facilitates the Otub1 binding to UbcH5 and likely inhibits ubiquitin chain transfer [XREF_BIBR], providing a mechanism underlying the Otub1 inhibition of E2 activity."
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"We next directly tested whether OTUB1 inhibited ubiquitin transfer to YTHDF2 with an in vitro ubiquitination reaction reported previously ( xref )."
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"OTUB1 suppresses the E3 ubiquitin-ligase by co-opting K48 ubiquitin recognition to regulate DNA damage [76,129,130,131,132]."
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"Further biochemical study found OTUB1 inhibits ubiquitin transfer from E2s to acceptor ubiquitin, thus blocking the formation of poly-ubiquitin chains."
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"The OTUB1 protein interacts directly with the E2 ubiquitin conjugating protein UBC13 and prevents ubiquitin transfer, thereby inhibiting double-strand-break-induced chromatin ubiquitination XREF_BIBR, XREF_BIBR."
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"Later, several structural studies independently revealed how OTUB1 inhibits ubiquitin transfer from E2."
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"We next directly tested whether OTUB1 inhibited ubiquitin transfer to YTHDF2 with an in vitro ubiquitination reaction reported previously (33)."
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"OTUB1 also inhibits ubiquitin transfer to the substrate by binding to the E2-Ub complex, independent of DUB activity [ xref ]."
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"In that respect, OTUB1 was described recently to inhibit Ub chain conjugation, independently of its catalytic activity, through direct binding to the E2 ubiquitin-conjugating enzyme UBC13 (Nakada et al, 2010)."
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"OTUB1 prevents transfer of ubiquitin from E2s to E3s."
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"We detected decreases in ubiquitin carboxy-terminal hydrolase L1, ubiquitin thioesterase OTUB1, and proteasome subunit alpha types 1 and 3 in cerebral ischemic damage."
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"Here we elucidate the structural mechanism by which OTUB1 binds E2s to inhibit ubiquitin transfer."
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"We next investigated whether OTUB1 inhibits E2 by preventing the conjugation of ubiquitin or the transfer of ubiquitin from E2 to E3."
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"An OTUB1 T134R substitution in the catalytic OTU domain that disrupts binding to UBCH5B was previously shown to reduce OTUB1 inhibition of UBCH5B ubiquitin conjugating activity xref ."
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"However, when wild-type OTUB1 is added to the reaction at the start, some ubiquitin is observed at its native molecular weight, whereas a significant amount of ubiquitin loaded E2 is also observed, suggesting that OTUB1 inhibits the transfer of ubiquitin from the E2-Ub complex to E3 (XREF_FIG)."
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"These results suggest that by binding to E2 ubiquitin conjugating enzymes, OTUB1 appears to inhibit the transfer of ubiquitin from E2-Ub complex onto E3 ubiquitin ligases."
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"Through binding to a subset of ubiquitin-charged E2s, OTUB1 prevents ubiquitin transfer by trapping the ubiquitin-charged E2."
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"In addition to such enzymatic ubiquitin deconjugation, the DUB OTUB1 limits ubiquitin signaling by direct inhibition of the ubiquitin conjugating enzyme UBC13 [68-70], while the ubiquitin E3 ligase RN[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"This conformational change promotes binding of the conjugated donor ubiquitin in the E2-Ub complex to OTUB1, thus blocking ubiquitin transfer from E2s to the substrate ( Juang et al., 2012 ; Wiener et[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"We further showed that OTUB1, by binding to UBE2D1, inhibits the transfer of ubiquitin from E2-Ub conjugate to E3 ubiquitin ligase NEDD4L and subsequently to SMAD3 (XREF_FIG)."
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"OTUB1 binds to a subset of E2 ubiquitin-conjugating enzymes and inhibits their activity by trapping the E2~ubiquitin thioester and preventing ubiquitin transfer."
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"In contrast to BRCC36, USP16 and USP3, OTUB1 inhibits the DSB ubiquitin response downstream of RNF8, at the level of RNF168."
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"OTUB1 directly inhibits ubiquitin-specific protease 8 (USP8) isopeptidase activity towards gene related to anergy in lymphocytes (GRAIL), a novel E3 ligase involved in the induction of anergy in CD4 T[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"In addition to its deubiquitinating activity, OTUB1 has the unique ability to bind to a subset of E2 ubiquitin-conjugating enzymes and inhibit ubiquitin transfer in a manner that does not depend upon the catalytic activity of OTUB1 (17–19)."
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"OTUB1 inhibits UBE2N by binding to the charged E2∼Ub thioester intermediate and preventing ubiquitin transfer (17, 19, 20)."
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"Later, several structural studies independently revealed how OTUB1 inhibits ubiquitin transfer from E2."
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"This occurs by different molecular mechanisms and requires catalytic activity of USP15, but not that of OTUB1, which rather binds to and inhibits the ubiquitin conjugating activity of the cognate E2 enzyme [XREF_BIBR, XREF_BIBR]."
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