TY - JOUR
T1 - Bmi1 Regulates IκBα Degradation via Association with the SCF Complex
AU - Okuyama, Yuko
AU - Jiang, Jing Jing
AU - Kamimura, Daisuke
AU - Nakamura, Akihiro
AU - Ogura, Hideki
AU - Atsumi, Toru
AU - Murakami, Masaaki
AU - Murakami, Masaaki
N1 - Funding Information:
This work was supported by a KAKENHI grant (to D.K., T.A., and M.M.), the Takeda Science Foundation (to M.M.), the Institute for Fermentation Osaka (to M.M.), the Mitsubishi Foundation (to M.M.), the Waksman Foundation of Japan (to M.M.), the Mochida Memorial Foundation for Medical and Pharmaceutical Research (to D.K.), the Takeshi Nagao Intractable Diseases Research Fund (to Y.T.), the Tokyo Medical Research Foundation (to M.M.), the Japan Science and Technology Agency–Centers of Research Excellence in Science and Technology Program (to M.M.), and the Osaka Foundation for the Promotion of Clinical Immunology (to M.M.).
Publisher Copyright:
Copyright © 2018 by The American Association of Immunologists, Inc.
PY - 2018/10/15
Y1 - 2018/10/15
N2 - 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 IκBα 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.
AB - 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 IκBα 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.
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U2 - 10.4049/jimmunol.1701223
DO - 10.4049/jimmunol.1701223
M3 - Article
C2 - 30209188
AN - SCOPUS:85054771652
VL - 201
SP - 2264
EP - 2272
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 8
ER -