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

Research output: Contribution to journalArticlepeer-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 languageEnglish
Pages (from-to)2264-2272
Number of pages9
JournalJournal of Immunology
Volume201
Issue number8
DOIs
Publication statusPublished - 2018 Oct 15

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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