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BAP1 binds IRAK1. 27 / 27
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"Mechanistically, BAP1 directly binds to IRAK1, competitively inhibits the interaction between IRAK1 and IRAK4, significantly prevents phosphorylation at Thr209 and Thr378 of IRAK1, as well as the autophosphorylation of IRAK1, impeding the dissociation of IRAK1 from the Myddosome complex and the sequential activation NF-κB signaling.Previous studies have demonstrated that IRAK1 undergoes phosphorylation and K63-linked ubiquitination during activation, both of which are essential for the initiation of downstream signaling pathways30, 41."
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"Considering that BAP1 can inhibit the above process without requiring enzymatic activity, we hypothesize that BAP1 likely binds to IRAK1 in a competitive manner with IRAK4."
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"Furthermore, ectopically overexpressed Flag-IRAK1 interacted solely with BAP1 and not with other members of the PR-DUB complex, ASXL1-3 (Fig. xref E-F), indicating a specific interaction between BAP1 and IRAK1."
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"The BAP1-IRAK1 interaction primarily takes place in the cytoplasm (Fig. xref H), where BAP1 is enzymatically inactive in the absence of ASXLs."
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"Together, we identified the protein-protein interaction between BAP1 and IRAK1 in cytoplasm and elucidated that BAP1 might repress NF-κB through IRAK1."
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"To prove this, we silenced/overexpressed IRAK4 and detected whether the binding of BAP1 and IRAK1 was affected."
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"We then tested if the phosphorylation status of IRAK1(T209) would affect BAP1-IRAK1 interaction."
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"Lipopolysaccharide (LPS) treatment significantly increased the phosphorylation at IRAK1(T209) as expected, but also substantially inhibited the interaction between BAP1 and IRAK1 (Fig. xref D)."
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"Consistently, λ-phosphatase treatment prominently enhanced BAP1-IRAK1 interaction (Fig. xref E)."
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"The interaction between BAP1 and IRAK1 is closely related to the phosphorylation status of IRAK1."
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"Our data suggests that BAP1-IRAK1 interaction inhibited IRAK1-T209 phosphorylation (Figure xref H-I)."
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"BAP1 binds to IRAK1 and inhibits the interaction between IRAK4 and IRAK1, as well as the IRAK4-mediated initiation of IRAK1 phosphorylation and autophosphorylation."
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"BAP1 interacts with IRAK1 in cytoplasm."
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"We validated the protein-protein interaction between BAP1 and IRAK1 through reciprocal co-immunoprecipitation (Co-IP) in endogenous and exogenous level (Fig. xref C-E)."
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"We demonstrated that ectopically over-expressed HA-BAP1 only interacted with IRAK1, but not MyD88 or IRAK4."
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"Co-IP assay indicated that silenced IRAK4 increased the binding of BAP1 with IRAK1, while overexpression of IRAK4 inhibited the interaction between BAP1 and IRAK1 (Fig. xref D-E)."
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"Since the interaction between BAP1 and IRAK1 is largely influenced by the phosphorylation status of IRAK1, we hypothesize that this negatively charged amino acid sequence on BAP1 may be crucial for the formation of the BAP1-IRAK1 complex."
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"BAP1 binds to IRAK1 and inhibits the interaction between IRAK4 and IRAK1, as well as the IRAK4-mediated initiation of IRAK1 phosphorylation and autophosphorylation."
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"IRAK4 mediated IRAK1phosphorylation impedes IRAK1-BAP1 interaction."
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"We validated the protein-protein interaction between BAP1 and IRAK1 through reciprocal co-immunoprecipitation (Co-IP) in endogenous and exogenous level (Fig. 4C-E)."
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"Furthermore, ectopically overexpressed Flag-IRAK1 interacted solely with BAP1 and not with other members of the PR-DUB complex, ASXL1-3 (Fig. 4E-F), indicating a specific interaction between BAP1 and IRAK1."
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"Co-IP assay indicated that silenced IRAK4 increased the binding of BAP1 with IRAK1, while overexpression of IRAK4 inhibited the interaction between BAP1 and IRAK1 (Fig. 6D-E)."
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"Since the interaction between BAP1 and IRAK1 is largely influenced by the phosphorylation status of IRAK1, we hypothesize that this negatively charged amino acid sequence on BAP1 may be crucial for the formation of the BAP1-IRAK1 complex."
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"Together, we identified the protein-protein interaction between BAP1 and IRAK1 in cytoplasm and elucidated that BAP1 might repress NF-κB through IRAK1."
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"Lipopolysaccharide (LPS) treatment significantly increased the phosphorylation at IRAK1(T209) as expected, but also substantially inhibited the interaction between BAP1 and IRAK1 (Fig. 5D)."
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"The interaction between BAP1 and IRAK1 is closely related to the phosphorylation status of IRAK1."
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"Considering that BAP1 can inhibit the above process without requiring enzymatic activity, we hypothesize that BAP1 likely binds to IRAK1 in a competitive manner with IRAK4.To prove this, we silenced/overexpressed IRAK4 and detected whether the binding of BAP1 and IRAK1 was affected."
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