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AMP-activated protein kinase-regulated phosphorylation and acetylation of importin alpha1 - Involvement in the nuclear import of RNA-binding protein HuR

Item Type:Article
Title:AMP-activated protein kinase-regulated phosphorylation and acetylation of importin alpha1 - Involvement in the nuclear import of RNA-binding protein HuR
Creators Name:Wang, W.G. and Yang, X.L. and Kawai, T. and de Silanes, I.L. and Mazan-Mamczarz, K. and Chen, P.L. and Chook, Y.M. and Quensel, C. and Koehler, M. and Gorospe, M.
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.
Keywords:Acetylation, Alpha Karyopherins, Aminoimidazole Carboxamide, Cell Line, Cell Nucleus Active Transport, Enzyme Activation, Histone Deacetylases, Lysine, Multienzyme Complexes, Nuclear Proteins, Phosphorylation, Protein-Serine-Threonine Kinases, Recombinant Fusion Proteins, Ribonucleotides, RNA Stability, Messenger RNA, RNA-Binding Proteins, Serine, Site-Directed Mutagenesis, Surface Antigens, Trans-Activators
Source:Journal of Biological Chemistry
ISSN:0021-9258
Publisher:American Society for Biochemistry and Molecular Biology (U.S.A.)
Volume:279
Number:46
Page Range:48376-48388
Date:1 January 2004
Official Publication:https://doi.org/10.1074/jbc.M409014200
PubMed:View item in PubMed

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