First Author | Hu H | Year | 2013 |
Journal | Nature | Volume | 494 |
Issue | 7437 | Pages | 371-4 |
PubMed ID | 23334419 | Mgi Jnum | J:194553 |
Mgi Id | MGI:5474156 | Doi | 10.1038/nature11831 |
Citation | Hu H, et al. (2013) OTUD7B controls non-canonical NF-kappaB activation through deubiquitination of TRAF3. Nature 494(7437):371-4 |
abstractText | The non-canonical NF-kappaB pathway forms a major arm of NF-kappaB signalling that mediates important biological functions, including lymphoid organogenesis, B-lymphocyte function, and cell growth and survival. Activation of the non-canonical NF-kappaB 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-kappaB pathway. OTUD7B deficiency in mice has no appreciable effect on canonical NF-kappaB activation but causes hyperactivation of non-canonical NF-kappaB. In response to non-canonical NF-kappaB stimuli, OTUD7B binds and deubiquitinates TRAF3, thereby inhibiting TRAF3 proteolysis and preventing aberrant non-canonical NF-kappaB 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-kappaB activation and indicate a mechanism of immune regulation that involves OTUD7B-mediated deubiquitination and stabilization of TRAF3. |