Nuclear retention of importin alpha coordinates cell fate through changes in gene expression

Yoshinari Yasuda, Yoichi Miyamoto, Tomoko Yamashiro, Munehiro Asally, Ayumi Masui, Chin Wong, Katherine A L Loveland, Yoshihiro Yoneda

Research output: Contribution to journalArticleResearchpeer-review

47 Citations (Scopus)

Abstract

Various cellular stresses including oxidative stress induce a collapse of the Ran gradient, which causes accumulation of importin alpha in the nucleus and a subsequent block of nuclear protein import. However, it is unknown whether accumulated importin alpha performs roles in the nucleus after its migration in response to stress. In this study, we found that nuclear-retained importin alpha2 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 alpha2 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 alpha2 influences gene expression and contributes directly to cell fate outcomes including non-apoptotic cell death.
Original languageEnglish
Pages (from-to)83 - 94
Number of pages12
JournalThe EMBO Journal
Volume31
Issue number1
DOIs
Publication statusPublished - 2012

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