OTUD7B controls non-canonical NF-κB activation through deubiquitination of TRAF3

Hongbo Hu, George C. Brittain, Jae Hoon Chang, Nahum Puebla-Osorio, Jin Jin, Anna Zal, Yichuan Xiao, Xuhong Cheng, Mikyoung Chang, Yang Xin Fu, Tomasz Zal, Chengming Zhu, Shao Cong Sun

Research output: Contribution to journalArticlepeer-review

176 Scopus citations


The non-canonical NF-κB pathway forms a major arm of NF-κB signalling that mediates important biological functions, including lymphoid organogenesis, B-lymphocyte function, and cell growth and survival. Activation of the non-canonical NF-κB pathway involves degradation of an inhibitory protein, TNF receptor-associated factor 3 (TRAF3), but how this signalling event is controlled is still unknown. Here we have identified the deubiquitinase OTUD7B as a pivotal regulator of the non-canonical NF-κB pathway. OTUD7B deficiency in mice has no appreciable effect on canonical NF-κB activation but causes hyperactivation of non-canonical NF-κB. In response to non-canonical NF-κB stimuli, OTUD7B binds and deubiquitinates TRAF3, thereby inhibiting TRAF3 proteolysis and preventing aberrant non-canonical NF-κB activation. Consequently, the OTUD7B deficiency results in B-cell hyper-responsiveness to antigens, lymphoid follicular hyperplasia in the intestinal mucosa, and elevated host-defence ability against an intestinal bacterial pathogen, Citrobacter rodentium. These findings establish OTUD7B as a crucial regulator of signal-induced non-canonical NF-κB activation and indicate a mechanism of immune regulation that involves OTUD7B-mediated deubiquitination and stabilization of TRAF3.

Original languageEnglish (US)
Pages (from-to)371-374
Number of pages4
Issue number7437
StatePublished - Feb 21 2013

ASJC Scopus subject areas

  • General


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