Bmi1 Regulates I{kappa}B{alpha} Degradation via Association with the SCF Complex [IMMUNE REGULATION]

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-B pathway. In this study, we report a novel function of Bmi1: its regulation of IBα ubiquitination in the cytoplasm. A deficiency of Bmi1 inhibited NF-B–mediated gene expression in vitro and a NF-B–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 IKKα/β-dependent pathway, leading to the ubiquitination of IBα. These effects on NF-B–related inflammation suggest Bmi1 in the SCF complex is a potential therapeutic target for various diseases and disorders, including autoimmune diseases.

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