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

The transcription factor NF-B regulates many biological processesand when deregulated contributes to the pathogenesis of various diseases. This study shows that the deubiquitinase OTUD7B specifically controls one of the major pathways of NF-B activation, the non-canonical or alternative pathway, by inhibiting TRAF3 proteolysis. OTUD7B deficiency in mice causes severe abnormalities in antibody production and intestinal homeostasis. These findings point to OTUD7B as a potentially attractive therapeutic target for drugs to boost mucosal immunity and treat diseases associated with the non-canonical NF-B pathway.