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Biochem Biophys Res Commun. 2010 Feb 12;392(3):409-14. doi: 10.1016/j.bbrc.2010.01.037. Epub 2010 Jan 15.

NUMBL interacts with TRAF6 and promotes the degradation of TRAF6.

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  • 1School of Life Sciences, Fudan University, Shanghai 200433, People's Republic of China.


Tumor necrosis factor-associated factor 6 (TRAF6) is an essential adaptor protein for IL-1R or TLR-mediated NF-kappaB signaling pathway activation. In previous work we have found NUMBL interacts with TAB2 and negatively regulates NF-kappaB signaling pathway. Here, we report that NUMBL directly binds to TRAF6 in vivo and in vitro. NUMBL down-regulates TRAF6 protein level and shortens its half-life. Furthermore, knockdown of NUMBL significantly increases endogenous TRAF6 protein level in the cultured cortical neurons. In vivo ubiquitination assays indicate that NUMBL promotes the assembly of K48-linked polyubiquitination chains on TRAF6, but has no significant effect on its K63-linked polyubiquitination. Our results collectively reveal that NUMBL interacts with TRAF6 and promotes the degradation of TRAF6 in vivo, leading to the inhibition of NF-kappaB signaling pathway.

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