Bmi1 Regulates I kappa B alpha Degradation via Association with the SCF Complex

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