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PMID: 11971974 Published · ppublish English Journal Article

AMP-activated kinase regulates cytoplasmic HuR.

Molecular and cellular biology ·Vol. 22 ·No. 10 ·2002-05-00 ·Pages 3425-36

Wang W, Fan J, Yang X, Fürer-Galban S, Lopez de Silanes I, von Kobbe C, Guo J, Georas SN, Foufelle F, Hardie DG, Carling D, Gorospe M

Abstract

While transport of RNA-binding protein HuR from nucleus to cytoplasm is emerging as a key regulatory step for HuR function, the mechanisms underlying this process remain poorly understood. Here, we report that the AMP-activated kinase (AMPK), an enzyme involved in responding to metabolic stresses, potently regulates the levels of cytoplasmic HuR. Inhibition of AMPK, accomplished either through cell treatment or by adenovirus infection to express dominant-negative AMPK, was found to increase the level of HuR in the cytoplasm and to enhance the binding of HuR to p21, cyclin B1, and cyclin A mRNA transcripts and elevate their expression and half-lives. Conversely, AMPK activation, achieved by means including infection to express constitutively active AMPK, resulted in reduced cytoplasmic HuR; decreased levels and half-lives of mRNAs encoding p21, cyclin A, and cyclin B1; and diminished HuR association with the corresponding transcripts. We therefore propose a novel function for AMPK as a regulator of cytoplasmic HuR levels, which in turn influences the mRNA-stabilizing function of HuR and the expression of HuR target transcripts.

MeSH Terms
3' Untranslated Regions/genetics AMP-Activated Protein Kinases Adenoviridae/genetics,metabolism Antigens, Surface Cell Division/physiology Cell Fractionation Cyclins/metabolism ELAV Proteins ELAV-Like Protein 1 Enzyme Inhibitors/metabolism Humans Multienzyme Complexes/genetics,metabolism Protein Binding Protein Serine-Threonine Kinases/genetics,metabolism Protein Transport/physiology RNA/metabolism RNA-Binding Proteins/metabolism Signal Transduction/physiology Tumor Cells, Cultured
Chemicals
3' Untranslated Regions Antigens, Surface Cyclins ELAV Proteins ELAV-Like Protein 1 ELAVL1 protein, human Enzyme Inhibitors Multienzyme Complexes RNA-Binding Proteins RNA Protein Serine-Threonine Kinases AMP-Activated Protein Kinases
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Wang Wengong
Laboratory of Cellular and Molecular Biology, National Institute on Aging-Internal Research Program, National Institutes of Health, Baltimore, Mayland 21224-6825, USA.
Fan Jinshui
Yang Xiaoling
Fürer-Galban Stefanie
Lopez de Silanes Isabel
von Kobbe Cayetano
Guo Jia
Georas Steve N
Foufelle Fabienne
Hardie D Grahame
Carling David
Gorospe Myriam
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.22.10.3425-3436.2002
Published
2002-05-00
Pages
3425-36
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC133799
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.22.10.3425-3436.2002 PMC Full Text View journal details
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