Bmi1 Regulates IκBα Degradation via Association with the SCF Complex

Yuko Okuyama; Jing Jing Jiang; Daisuke Kamimura; Akihiro Nakamura; Hideki Ogura; Toru Atsumi; Masaaki Murakami; Masaaki Murakami

doi:10.4049/jimmunol.1701223

Bmi1 Regulates IκBα Degradation via Association with the SCF Complex

Yuko Okuyama, Jing Jing Jiang, Daisuke Kamimura, Akihiro Nakamura, Hideki Ogura, Toru Atsumi, Masaaki Murakami, Masaaki Murakami

MED - Medical Sciences

Research output: Contribution to journal › Article › peer-review

3 Citations (Scopus)

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 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.

Original language	English
Pages (from-to)	2264-2272
Number of pages	9
Journal	Journal of Immunology
Volume	201
Issue number	8
DOIs	https://doi.org/10.4049/jimmunol.1701223
Publication status	Published - 2018 Oct 15

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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title = "Bmi1 Regulates IκBα Degradation via Association with the SCF Complex",

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 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.",

author = "Yuko Okuyama and Jiang, {Jing Jing} and Daisuke Kamimura and Akihiro Nakamura and Hideki Ogura and Toru Atsumi and Masaaki Murakami and Masaaki Murakami",

note = "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.).",

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AU - Okuyama, Yuko

AU - Jiang, Jing Jing

AU - Kamimura, Daisuke

AU - Nakamura, Akihiro

AU - Ogura, Hideki

AU - Atsumi, Toru

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.).

PY - 2018/10/15

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