IndraLab

Statements

TRAF6 binds USP14. 19 / 19
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"However, USP14 and TRAF6 interaction was not affected by TRAF6 ubiquitin-ligase activity or TRAF6 autoubiquitination."
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"Therefore, it is concluded that S5 treatment directly inhibits the deubiquitinating enzymic activity of USP14, especially blocks USP14–TRAF6 interaction, and increases of TRAF6–Beclin1 association, which results in K63-linked ubiquitination of Beclin1 and autophagy."
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"Since USP14 interacted with the CC domain of TRAF6 (Figure xref E), we examined whether USP14 induced deubiquitination of TRAF6."
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"Based on this result, we further examined whether TRAF6 and USP14 interaction might affect ubiquitination of Beclin 1."
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"We found that USP14 interacted with TRAF6."
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"This complex was found to block the interaction of USP14 with TNF receptor associated factor 6 (TRAF6), subsequently promoting the ubiquitination of Beclin 1 by disturbing the Beclin 1-Bcl2 interaction ( xref )."
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"Based on this result, we further examined whether TRAF6 and USP14 interaction might affect ubiquitination of Beclin 1."
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"Furthermore, by multiple methods, S5 was revealed to directly bind with ubiquitin-specific proteases 14 (USP14) at Ser404, Phe405, and Cys414 by hydrogen bond to inhibit its deubiquitinating activity, and block USP14–TRAF6 (TNF receptor associated factor 6) interaction, subsequently promoting ubiquitination of Beclin1, interrupting Beclin1–Bcl2 interaction, and accumulating the autophagosome in macrophages, which finally resulted in the blockade of M1-like macrophage polarization."
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"And the inhibitory effect of S5 on USP14–TRAF6 interaction was also confirmed in HEK293T cells transfected with His-USP14 and HA-TRAF6 (Fig. xref )."
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"As shown in Figure xref E, Flag-TRAF6 wt, Flag-TRAF6 110-522, and Flag-TRAF6 260-522, but not Flag-TRAF6 349-522, were co-precipitated with Myc-USP14, indicating that USP14 interacted with the CC domain of TRAF6."
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"Our results showed that S5 dose-dependently decreased USP14–TRAF6 interaction, while increased TRAF6–Beclin1 interaction simultaneously (Fig. xref )."
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"We found that USP14 interacted with the CC domain of TRAF6."
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"Since TRAF6 interacts with Beclin 1 and TRAF6 mediated ubiquitination of Beclin 1 is critical for autophagy induction, USP14 and Beclin 1 might competitively interact with the CC domain of TRAF6 and affect TRAF6 mediated ubiquitination of Beclin 1."
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"Although USP14 and TRAF6 interaction did not affect TRAF6 ubiquitination, we found that USP14 interacted with TAB 2 and induced deubiquitination of TAB 2."
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"We found that USP14 interacted with TRAF6."
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"Consequently, our result showed that S5 interrupted USP14–TRAF6 interaction, and simultaneously enhanced TRAF6–Beclin1 interaction (Fig. xref )."
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"However, USP14 and TRAF6 interaction was not affected by TRAF6 ubiquitin-ligase activity or TRAF6 autoubiquitination."
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"Although USP14 and TRAF6 interaction did not affect TRAF6 ubiquitination, we found that USP14 interacted with TAB 2 and induced deubiquitination of TAB 2."
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"This was because that S5 not only inhibited deubiquitinating enzymic activity of USP14, but also greatly blocked USP14–TRAF6 interaction, which led to obvious TRAF6–Beclin1 interaction and facilitation of Beclin1 ubiquitination."
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