OTUD7B controls non-canonical NF-kappa B activation through deubiquitination of TRAF3

Title
OTUD7B controls non-canonical NF-kappa B activation through deubiquitination of TRAF3
Author(s)
장재훈Hongbo Hu[Hongbo Hu]George C. Brittain[George C. Brittain]Nahum Puebla-Osorio[Nahum Puebla-Osorio]Jin Jin[Jin Jin]Anna Zal[Anna Zal]Yichuan Xiao[Yichuan Xiao]Xuhong Cheng[Xuhong Cheng]Mikyoung Chang[Mikyoung Chang]Tomasz Zal[Tomasz Zal]Chengming Zhu [Chengming Zhu ]Yang-Xin Fu[Yang-Xin Fu]Shao-Cong Sun[Shao-Cong Sun]
Keywords
LYMPHOTOXIN-BETA-RECEPTOR; HOMEOSTASIS; PATHWAY; KINASE; RESPONSES; CEZANNE; NIK
Issue Date
201302
Publisher
NATURE PUBLISHING GROUP
Citation
NATURE, v.494, no.7437, pp.371 - 374
Abstract
The non-canonical NF-kappa B pathway forms a major arm of NF-kappa B signalling that mediates important biological functions, including lymphoid organogenesis, B-lymphocyte function, and cell growth and survival(1-3). Activation of the non-canonical NF-kappa B pathway involves degradation of an inhibitory protein, TNF receptor-associated factor 3 (TRAF3), but how this signalling event is controlled is still unknown(1,2). Here we have identified the deubiquitinase OTUD7B as a pivotal regulator of the non-canonical NF-kappa B pathway. OTUD7B deficiency in mice has no appreciable effect on canonical NF-kappa B activation but causes hyperactivation of non-canonical NF-kappa B. In response to non-canonical NF-kappa B stimuli, OTUD7B binds and deubiquitinates TRAF3, thereby inhibiting TRAF3 proteolysis and preventing aberrant non-canonical NF-kappa B 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-kappa B activation and indicate a mechanism of immune regulation that involves OTUD7B-mediated deubiquitination and stabilization of TRAF3.
URI
http://hdl.handle.net/YU.REPOSITORY/26416http://dx.doi.org/10.1038/nature11831
ISSN
0028-0836
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약학대학 > 약학부 > Articles
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