%0 Journal Article
%T Preventing abnormal NF-百B activation and autoimmunity by Otub1-mediated p100 stabilization
%J -
%D 2019
%R https://doi.org/10.1038/s41422-019-0174-3
%X NF-百B, a family of transcription factors regulating diverse biological processes including immune responses, is activated by canonical and noncanonical pathways based on degradation of I百B汐 and processing of the I百B-like protein p100, respectively. Although p100 responds to noncanonical NF-百B stimuli for processing, it does not undergo degradation, but rather becomes accumulated, along with canonical NF-百B activation. We show here that the stability of p100 is tightly controlled by a deubiquitinase, Otub1. Otub1 deficiency not only promotes signal-induced p100 processing and noncanonical NF-百B activation but also causes steady-state p100 degradation, leading to aberrant NF-百B activation in the canonical pathway. B-cell-conditional deletion of Otub1 results in B-cell hyperplasia, antibody hyper-production, and lupus-like autoimmunity. Otub1-deficient B cells display aberrantly activated phenotypes and overproduce the cytokine IL-6, contributing to autoimmunity induction. Thus, maintenance of p100 stability by Otub1 serves as an unusual mechanism of NF-百B regulation that prevents autoimmunity
%U https://www.nature.com/articles/s41422-019-0174-3