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Molecular and Cellular Biology, May 2002, p. 3425-3436, Vol. 22, No. 10
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.10.3425-3436.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

AMP-Activated Kinase Regulates Cytoplasmic HuR

Wengong Wang,1 Jinshui Fan,1 Xiaoling Yang,1 Stefanie Fürer-Galban,1 Isabel Lopez de Silanes,1 Cayetano von Kobbe,2 Jia Guo,3 Steve N. Georas,3 Fabienne Foufelle,4 D. Grahame Hardie,5 David Carling,6 and Myriam Gorospe1*

Laboratory of Cellular and Molecular Biology and,1 Laboratory of Molecular Gerontology, National Institute on Aging-Internal Research Program, National Institutes of Health,2 Division of Pulmonary and Critical Care Medicine, Johns Hopkins Asthma and Allergy Center, Baltimore, Maryland 21224,3 Unité 465 INSERM, Centre de Recherches Biomedicales des Cordeliers, 75270 Paris Cedex 06, France,4 School of Life Sciences and Wellcome Trust Biocentre, University of Dundee, Dundee DD1 5EH, Scotland,5 MRC Clinical Sciences Centre, Imperial College School of Medicine, London W12 0NN, United Kingdom6

Received 28 November 2001/ Returned for modification 11 January 2002/ Accepted 14 February 2002

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.

* Corresponding author. Mailing address: Box 12, LCMB, NIA, National Institutes of Health, 5600 Nathan Shock Dr., Baltimore, MD 21224-6825. Phone: (410) 558-8443. Fax: (410) 558-8386. E-mail: myriam-gorospe{at}nih.gov.

Molecular and Cellular Biology, May 2002, p. 3425-3436, Vol. 22, No. 10
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.10.3425-3436.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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