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

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Abstract

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
JournalNature
Volume494
Issue number7437
DOIs
StatePublished - Feb 21 2013

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TNF Receptor-Associated Factor 3
B-Lymphocytes
Proteolysis
Citrobacter rodentium
Organogenesis
Intestinal Mucosa
Hyperplasia
Cell Survival
Antigens
Growth

ASJC Scopus subject areas

  • General

Cite this

Hu, H., Brittain, G. C., Chang, J. H., Puebla-Osorio, N., Jin, J., Zal, A., ... Sun, S. C. (2013). OTUD7B controls non-canonical NF-κB activation through deubiquitination of TRAF3. Nature, 494(7437), 371-374. https://doi.org/10.1038/nature11831

OTUD7B controls non-canonical NF-κB activation through deubiquitination of TRAF3. / Hu, Hongbo; Brittain, George C.; Chang, Jae Hoon; Puebla-Osorio, Nahum; Jin, Jin; Zal, Anna; Xiao, Yichuan; Cheng, Xuhong; Chang, Mikyoung; Fu, Yang Xin; Zal, Tomasz; Zhu, Chengming; Sun, Shao Cong.

In: Nature, Vol. 494, No. 7437, 21.02.2013, p. 371-374.

Research output: Contribution to journalArticle

Hu, H, Brittain, GC, Chang, JH, Puebla-Osorio, N, Jin, J, Zal, A, Xiao, Y, Cheng, X, Chang, M, Fu, YX, Zal, T, Zhu, C & Sun, SC 2013, 'OTUD7B controls non-canonical NF-κB activation through deubiquitination of TRAF3', Nature, vol. 494, no. 7437, pp. 371-374. https://doi.org/10.1038/nature11831
Hu H, Brittain GC, Chang JH, Puebla-Osorio N, Jin J, Zal A et al. OTUD7B controls non-canonical NF-κB activation through deubiquitination of TRAF3. Nature. 2013 Feb 21;494(7437):371-374. https://doi.org/10.1038/nature11831
Hu, Hongbo ; Brittain, George C. ; Chang, Jae Hoon ; Puebla-Osorio, Nahum ; Jin, Jin ; Zal, Anna ; Xiao, Yichuan ; Cheng, Xuhong ; Chang, Mikyoung ; Fu, Yang Xin ; Zal, Tomasz ; Zhu, Chengming ; Sun, Shao Cong. / OTUD7B controls non-canonical NF-κB activation through deubiquitination of TRAF3. In: Nature. 2013 ; Vol. 494, No. 7437. pp. 371-374.
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