| First Author | Li Y | Year | 2019 |
| Journal | Cell Res | Volume | 29 |
| Issue | 6 | Pages | 474-485 |
| PubMed ID | 31086255 | Mgi Jnum | J:280549 |
| Mgi Id | MGI:6369872 | Doi | 10.1038/s41422-019-0174-3 |
| Citation | Li Y, et al. (2019) Preventing abnormal NF-kappaB activation and autoimmunity by Otub1-mediated p100 stabilization. Cell Res 29(6):474-485 |
| abstractText | NF-kappaB, a family of transcription factors regulating diverse biological processes including immune responses, is activated by canonical and noncanonical pathways based on degradation of IkappaBalpha and processing of the IkappaB-like protein p100, respectively. Although p100 responds to noncanonical NF-kappaB stimuli for processing, it does not undergo degradation, but rather becomes accumulated, along with canonical NF-kappaB 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-kappaB activation but also causes steady-state p100 degradation, leading to aberrant NF-kappaB 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-kappaB regulation that prevents autoimmunity. |
