フジタ　トシハル   Toshiharu Fujita   藤田　敏治    所属   川崎医科大学  医学部 基礎医学　分子遺伝医学    職種   助教
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Importin alpha subtypes determine differential transcription factor localization in embryonic stem cells maintenance.
掲載誌名	正式名：Developmental cell 略　 称：Dev Cell ISSNコード：18781551/15345807
掲載区分	国外
巻・号・頁	26(2),pp.123-35
著者・共著者	Noriko Yasuhara, Ryosuke Yamagishi, Yoshiyuki Arai, Rashid Mehmood, Chihiro Kimoto, Toshiharu Fujita, Kenichi Touma, Azumi Kaneko, Yasunao Kamikawa, Tetsuji Moriyama, Toshio Yanagida, Hiroki Kaneko, Yoshihiro Yoneda
発行年月	2013/07
概要	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.
DOI	10.1016/j.devcel.2013.06.022
PMID	23906064