AMP-activated protein kinase-regulated phosphorylation and acetylation of importin α1: Involvement in the nuclear import of RNA-binding protein HuR

Wengong Wang, Xiaoling Yang, Tomoko Kawai, Isabel López De Silanes, Krystyna Mazan-Mamczarz, Peili Chen, Min Chook Yuh, Christina Quensel, Matthias Köhler, Myriam Gorospe

Research output: Contribution to journalArticle

100 Scopus citations

Abstract

Nuclear import of HuR, a shuttling RNA-binding protein, is associated with reduced stability of its target mRNAs. Increased function of the AMP-activated protein kinase (AMPK), an enzyme involved in responding to metabolic stress, was recently shown to reduce the cytoplasmic levels of HuR. Here, we provide evidence that importin α1, an adaptor protein involved in nuclear import, contributes to the nuclear import of HuR through two AMPK-modulated mechanisms. First, AMPK triggered the acetylation of importin α1 on Lys22, a process dependent on the acetylase activity of p300. Second, AMPK phosphorylated importin α1 on Ser105. Accordingly, expression of importin α1 proteins bearing K22R or S105A mutations failed to mediate the nuclear import of HuR in intact cells. Our results point to importin α1 as a critical downstream target of AMPK and key mediator of AMPK-triggered HuR nuclear import.

Original languageEnglish (US)
Pages (from-to)48376-48388
Number of pages13
JournalJournal of Biological Chemistry
Volume279
Issue number46
DOIs
StatePublished - Nov 12 2004

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Wang, W., Yang, X., Kawai, T., De Silanes, I. L., Mazan-Mamczarz, K., Chen, P., Yuh, M. C., Quensel, C., Köhler, M., & Gorospe, M. (2004). AMP-activated protein kinase-regulated phosphorylation and acetylation of importin α1: Involvement in the nuclear import of RNA-binding protein HuR. Journal of Biological Chemistry, 279(46), 48376-48388. https://doi.org/10.1074/jbc.M409014200