NUMBL interacts with TRAF6 and promotes the degradation of TRAF6.
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.
Zhou
Li
L
School of Life Sciences, Fudan University, Shanghai 200433, People's Republic of China.
Ma
Qi
Q
Shi
Huili
H
Huo
Keke
K
D002460:Cell Line; D002540:Cerebral Cortex / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D048029:TNF Receptor-Associated Factor 6 / Q000378:metabolism*; D054875:Ubiquitination
D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; C530266:NUMBL protein, human; D048029:TNF Receptor-Associated Factor 6