1. Bmi1 Regulates IκBα Degradation via Association with the SCF Complex.
- Author
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Yuko Okuyama, Jing-Jing Jiang, Daisuke Kamimura, Hideki Ogura, Toru Atsumi, Masaaki Murakami, Akihiro Nakamura, Yuki Tanaka, Mitsutoshi Ota, Takuto Ohki, Daisuke Higo, and Naoto Ishii
- Subjects
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POLYCOMB group proteins , *CYTOPLASM , *GENE expression , *ARTHRITIS , *CANCER stem cells , *AUTOIMMUNE diseases - Abstract
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-κB pathway. In this study, we report a novel function of Bmi1: its regulation of IkBa ubiquitination in the cytoplasm. A deficiency of Bmi1 inhibited NF-κB--mediated gene expression in vitro and a NF-κB--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 IκBα. These effects on NF-κB--related inflammation suggest Bmi1 in the SCF complex is a potential therapeutic target for various diseases and disorders, including autoimmune diseases. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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