Graduate School of Frontier Biosciences, Osaka University

Japanese

Importin Alpha Subtypes Determine Differential Transcription Factor Localization in Embryonic Stem Cells Maintenance

Journal Dev Cell 26, 123-135
Authors Noriko Yasuhara (1, 7, *), Ryosuke Yamagishi (6, 7), Yoshiyuki Arai (2), Rashid Mehmood (3), Chihiro Kimoto (3), Toshiharu Fujita (3), Kenichi Touma (3), Azumi Kaneko (3), Yasunao Kamikawa (3), Tetsuji Moriyama (3), Toshio Yanagida (2, 4), Hiroki Kaneko (6, *), Yoshihiro Yoneda (1, 3, 5)

  1. Department of Biochemistry, Graduate School of Medicine, Graduate School of Frontier Biosciences, Osaka University
  2. Soft Biosystem Group, Graduate School of Frontier Biosciences, Osaka University
  3. Biomolecular Dynamics Group, Graduate School of Frontier Biosciences, Osaka University
  4. Immunology Frontier Research Center, Graduate School of Frontier Biosciences, Osaka University
  5. JST-CREST, Graduate School of Frontier Biosciences, Osaka University
  6. Department of Integrated Sciences in Physics and Biology, College of Humanities and Sciences, Nihon University

*These authors contributed equally to this work.
Title The four-transmembrane protein IP39 of Euglena forms strands by a trimeric unit repeat
PubMed 23906064
Laboratory
Abstract We recently demonstrated that the expression of the importin α subtype is switched from α2 to α1 during neural differentiation in mouse embryonic stem cells (ESCs) and that this switching has a major impact on cell differentiation. In this study, we report a cell-fate determination mechanism in which importin α2 negatively regulates the nuclear import of certain transcription factors to maintain ESC properties. The nuclear import of Oct6 and Brn2 was inhibited via the formation of a transport-incompetent complex of the cargo bound to a nuclear localization signal binding site in importin α2. Unless this dominant-negative effect was downregulated upon ESC differentiation, inappropriate cell death was induced. We propose that although certain transcription factors are necessary for differentiation in ESCs, these factors are retained in the cytoplasm by importin α2, thereby preventing transcription factor activity in the nucleus until the cells undergo differentiation.