IndraLab

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USP18 deubiquitinates IKBKG. 11 / 11
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"To investigate the precise mechanisms mediating inhibition of NEMO ubiquitination by USP18, we generated NEMO deletion mutants (XREF_FIG), containing a domain responsible for IKK binding, TANK binding, UBAN, or IkappaBalpha binding."
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"On the other hand, USP18 inhibits NEMO ubiquitination by directly binding to its UBAN domain."
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"These results indicate that USP18 inhibits NEMO ubiquitination as well as NF-kappaB activity in a protease independent manner."
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"USP18 inhibits NEMO ubiquitination at the Lys -325 and 326 sites by masking the UBAN domain of NEMO."
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"Since the UBAN domain of NEMO contains all five K63 linked ubiquitination sites (Lys 285, Lys 321, Lys 325, Lys 326, and Lys 399) XREF_BIBR and two linear ubiquitination sites for NEMO (Lys 285 and Lys 309) XREF_BIBR, USP18 may prevent NEMO ubiquitination by masking these ubiquitination sites through direct binding."
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"Collectively, our findings revealed that USP18 inhibits TAK1 and NEMO ubiquitination through different mechanisms."
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"USP18 negatively regulates NF-κB signaling by targeting TAK1 and NEMO for deubiquitination through distinct mechanisms"
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"Another way that USP18 inhibited NF-κB activation is by deubiquitinating K63-Ub of TAK1 and NEMO [42] ."
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"First, we used the two-step immunoprecipitation assay to assess whether USP18 prevents the conjugated ubiquitination of NEMO."
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"We next tested whether USP18 inhibited NEMO ubiquitination through USP18 protease activity."
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"Conversely, USP18 inhibited NEMO ubiquitination by directly binding to its UBAN motif (ubiquitin binding in ABIN and NEMO) and masking its ubiquitination sites at Lys 325 and 326 from further K63 linked ubiquitination."
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