| First Author | Okuyama Y | Year | 2018 |
| Journal | J Immunol | Volume | 201 |
| Issue | 8 | Pages | 2264-2272 |
| PubMed ID | 30209188 | Mgi Jnum | J:266631 |
| Mgi Id | MGI:6203138 | Doi | 10.4049/jimmunol.1701223 |
| Citation | Okuyama Y, et al. (2018) Bmi1 Regulates IkappaBalpha Degradation via Association with the SCF Complex. J Immunol 201(8):2264-2272 |
| abstractText | Bmi1 is a polycomb group protein and regulator that stabilizes the ubiquitination complex PRC1 in the nucleus with no evidently direct link to the NF-kappaB pathway. In this study, we report a novel function of Bmi1: its regulation of IkappaBalpha ubiquitination in the cytoplasm. A deficiency of Bmi1 inhibited NF-kappaB-mediated gene expression in vitro and a NF-kappaB-mediated mouse model of arthritis in vivo. Mechanistic analysis showed that Bmi1 associated with the SCF ubiquitination complex via its N terminus and with phosphorylation by an IKKalpha/beta-dependent pathway, leading to the ubiquitination of IkappaBalpha. These effects on NF-kappaB-related inflammation suggest Bmi1 in the SCF complex is a potential therapeutic target for various diseases and disorders, including autoimmune diseases. |
