A nuclear export signal in the N-terminal regulatory domain of IκBα controls cytoplasmic localization of inactive NF-κB/IκBα complexes

DOI Web Site 被引用文献7件 オープンアクセス
  • Tony T. Huang
    Program in Molecular and Cellular Pharmacology, Department of Pharmacology, University of Wisconsin, K4/554 Clinical Sciences Center, 600 Highland Avenue, Madison, WI 53792; and Department of Biotechnology, Graduate School of Agriculture and Life Sciences, University of Tokyo, Bunkyo-ku Tokyo 113, Japan
  • Nobuaki Kudo
    Program in Molecular and Cellular Pharmacology, Department of Pharmacology, University of Wisconsin, K4/554 Clinical Sciences Center, 600 Highland Avenue, Madison, WI 53792; and Department of Biotechnology, Graduate School of Agriculture and Life Sciences, University of Tokyo, Bunkyo-ku Tokyo 113, Japan
  • Minoru Yoshida
    Program in Molecular and Cellular Pharmacology, Department of Pharmacology, University of Wisconsin, K4/554 Clinical Sciences Center, 600 Highland Avenue, Madison, WI 53792; and Department of Biotechnology, Graduate School of Agriculture and Life Sciences, University of Tokyo, Bunkyo-ku Tokyo 113, Japan
  • Shigeki Miyamoto
    Program in Molecular and Cellular Pharmacology, Department of Pharmacology, University of Wisconsin, K4/554 Clinical Sciences Center, 600 Highland Avenue, Madison, WI 53792; and Department of Biotechnology, Graduate School of Agriculture and Life Sciences, University of Tokyo, Bunkyo-ku Tokyo 113, Japan

書誌事項

公開日
2000-02
DOI
  • 10.1073/pnas.97.3.1014
公開者
Proceedings of the National Academy of Sciences

この論文をさがす

説明

<jats:p>Appropriate subcellular localization is crucial for regulation of NF-κB function. Herein, we show that latent NF-κB complexes can enter and exit the nucleus in preinduction states. The nuclear export inhibitor leptomycin B (LMB) sequestered NF-κB/IκBα complexes in the nucleus. Using deletion and site-directed mutagenesis, we identified a previously uncharacterized nuclear export sequence in residues 45–54 of IκBα that was required for cytoplasmic localization of inactive complexes. This nuclear export sequence also caused nuclear exclusion of heterologous proteins in a LMB-sensitive manner. Importantly, a LMB-insensitive CRM1 mutant (Crm1-K1) abolished LMB-induced nuclear accumulation of the inactive complexes. Moreover, a cell-permeable p50 NF-κB nuclear localization signal peptide also blocked these LMB effects. These results suggest that NF-κB/IκBα complexes shuttle between the cytoplasm and nucleus by a nuclear localization signal-dependent nuclear import and a CRM1-dependent nuclear export. The LMB-induced nuclear complexes could not bind DNA and were inaccessible to signaling events, because LMB inhibited NF-κB activation without affecting the subcellular localization of upstream kinases IKKβ and NIK. Our findings indicate that the dominant nuclear export over nuclear import contributes to the largely cytoplasmic localization of the inactive complexes to achieve efficient NF-κB activation by extracellular signals.</jats:p>

収録刊行物

被引用文献 (7)*注記

もっと見る

詳細情報 詳細情報について

問題の指摘

ページトップへ