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Nuclear retention of importin α coordinates cell fate through changes in gene expression
Author(s) -
Yasuda Yoshinari,
Miyamoto Yoichi,
Yamashiro Tomoko,
Asally Munehiro,
Masui Ayumi,
Wong Chin,
Loveland Kate L,
Yoneda Yoshihiro
Publication year - 2012
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2011.360
Subject(s) - biology , importin , gene , gene expression , cell nucleus , microbiology and biotechnology , genetics , nuclear pore , nuclear protein , nuclear transport , computational biology , nucleus , transcription factor
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.