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Nuclear retention of importin α coordinates cell fate through changes in gene expression
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Yasuda, Yoshinari, Miyamoto, Yoichi, Yamashiro, Tomoko, Asally, Munehiro, Masui, Ayumi, Wong, Chin, Loveland, Kate L and Yoneda, Yoshihiro (2011) Nuclear retention of importin α coordinates cell fate through changes in gene expression. The EMBO Journal, 31 (1). pp. 83-94. doi:10.1038/emboj.2011.360 ISSN 0261-4189.
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Official URL: http://dx.doi.org/10.1038/emboj.2011.360
Abstract
Various cellular stresses including oxidative stress induce a collapse of the Ran gradient, which causes accumulation of importin α in the nucleus and a subsequent block of nuclear protein import. However, it is unknown whether accumulated importin α performs roles in the nucleus after its migration in response to stress. In this study, we found that nuclear-retained importin α2 binds with DNase I-sensitive nuclear component(s) and exhibits selective upregulation of mRNA encoding Serine/threonine kinase 35 (STK35) by microarray analysis. Chromatin immunoprecipitation and promoter analysis demonstrated that importin α2 can access to the promoter region of STK35 and accelerate its transcription in response to hydrogen peroxide exposure. Furthermore, constitutive overexpression of STK35 proteins enhances caspase-independent cell death under oxidative stress conditions. These results collectively reveal that nuclear-localized importin α2 influences gene expression and contributes directly to cell fate outcomes including non-apoptotic cell death.
| Item Type: | Journal Article | |||||||||
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| Subjects: | Q Science > QD Chemistry Q Science > QH Natural history |
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| Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | |||||||||
| Library of Congress Subject Headings (LCSH): | Oxidative stress, Oxidation-reduction reaction, Nuclear proteins, Protein microarrays , Gene expression | |||||||||
| Journal or Publication Title: | The EMBO Journal | |||||||||
| Publisher: | Nature Publishing Group | |||||||||
| ISSN: | 0261-4189 | |||||||||
| Official Date: | 30 September 2011 | |||||||||
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| Volume: | 31 | |||||||||
| Number: | 1 | |||||||||
| Page Range: | pp. 83-94 | |||||||||
| DOI: | 10.1038/emboj.2011.360 | |||||||||
| Status: | Peer Reviewed | |||||||||
| Publication Status: | Published | |||||||||
| Access rights to Published version: | Restricted or Subscription Access | |||||||||
| Funder: | Japan. Monbu Kagakushō [Japan. Ministry of Education, Culture, Sports, Science and Technology] (MEXT), Kagaku Gijutsu Shinkō Kikō [Japan Science and Technology Agency] (JST), Takeda Kagaku Shinkō Zaidan [Takeda Science Foundation], Nihon Gakujutsu Shinkōkai [Japan Society for the Promotion of Science] (JSPS) | |||||||||
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