title: Nuclear retention of importin α coordinates cell fate through changes in gene expression.
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.
authors.affiliation: Department of Frontier Biosciences, Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan.
authors.forename: Yoshinari
authors.initials: Y
authors.lastname: Yasuda
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Miyamoto
authors.forename: Tomoko
authors.initials: T
authors.lastname: Yamashiro
authors.forename: Munehiro
authors.initials: M
authors.lastname: Asally
authors.forename: Ayumi
authors.initials: A
authors.lastname: Masui
authors.forename: Chin
authors.initials: C
authors.lastname: Wong
authors.forename: Kate L
authors.initials: KL
authors.lastname: Loveland
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Yoneda
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D015870:Gene Expression; D051379:Mice; D019913:Nuclear Localization Signals / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D018384:Oxidative Stress; D011494:Protein Kinases / Q000235:genetics* / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger / Q000378:metabolism; D014162:Transfection; D028901:alpha Karyopherins / Q000235:genetics / Q000378:metabolism*
chemical_list: D019913:Nuclear Localization Signals; D009687:Nuclear Proteins; D012333:RNA, Messenger; D028901:alpha Karyopherins; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; C470368:STK35 protein, human