JBC

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Originally published In Press as doi:10.1074/jbc.M409014200 on September 1, 2004

J. Biol. Chem., Vol. 279, Issue 46, 48376-48388, November 12, 2004
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
279/46/48376    most recent
M409014200v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Wang, W.
Right arrow Articles by Gorospe, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wang, W.
Right arrow Articles by Gorospe, M.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

AMP-activated Protein Kinase-regulated Phosphorylation and Acetylation of Importin {alpha}1

INVOLVEMENT IN THE NUCLEAR IMPORT OF RNA-BINDING PROTEIN HuR*

Wengong Wang{ddagger}§, Xiaoling Yang{ddagger}, Tomoko Kawai{ddagger}, Isabel López de Silanes{ddagger}, Krystyna Mazan-Mamczarz{ddagger}, Peili Chen¶, Yuh Min Chook||, Christina Quensel**, Matthias Köhler**{ddagger}{ddagger}, and Myriam Gorospe{ddagger}§§

From the {ddagger}Laboratory of Cellular and Molecular Biology, NIA Intramural Research Program, National Institutes of Health, Baltimore, Maryland 21224, the Sydney Kimmel Comprehensive Cancer Center, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21231, the ||Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, and the **HELIOS Clinic Franz Volhard Clinic at the Max Delbrueck Center for Molecular Medicine, 13125 Berlin, Germany

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 {alpha}1, 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 {alpha}1 on Lys22, a process dependent on the acetylase activity of p300. Second, AMPK phosphorylated importin {alpha}1 on Ser105. Accordingly, expression of importin {alpha}1 proteins bearing K22R or S105A mutations failed to mediate the nuclear import of HuR in intact cells. Our results point to importin {alpha}1as a critical downstream target of AMPK and key mediator of AMPK-triggered HuR nuclear import.

Received for publication, August 6, 2004 , and in revised form, September 1, 2004.

* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

{ddagger}{ddagger} The Deutsche Forschungsgemeinschaft (DFG Ko 1950/1-3) supported M. Köhler.

§ To whom correspondence may be addressed: Center for Vascular Biology, University of Connecticut Health Center, 263 Farmington Ave., Farmington, CT 06030-13501. Tel.: 860-679-8082; Fax: 860-679-1201; E-mail: wewang{at}uchc.edu. §§ To whom correspondence may be addressed: Box 12, LCMB, NIAIRP, National Institutes of Health, 5600 Nathan Shock Dr., Baltimore, MD 21224-6825. Tel.: 410-558-8050; Fax: 410-558-8386; E-mail: myriam-gorospe{at}nih.gov.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 Mol Cancer ResHome page
G. K. Scott, C. Marx, C. E. Berger, L. R. Saunders, E. Verdin, S. Schafer, M. Jung, and C. C. Benz
Destabilization of ERBB2 Transcripts by Targeting 3' Untranslated Region Messenger RNA Associated HuR and Histone Deacetylase-6
Mol. Cancer Res., July 1, 2008; 6(7): 1250 - 1258.
[Abstract] [Full Text] [PDF]

Home page
 Genes Dev.Home page
H. H. Kim, K. Abdelmohsen, A. Lal, R. Pullmann Jr., X. Yang, S. Galban, S. Srikantan, J. L. Martindale, J. Blethrow, K. M. Shokat, et al.
Nuclear HuR accumulation through phosphorylation by Cdk1
Genes & Dev., July 1, 2008; 22(13): 1804 - 1815.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Biol.Home page
R. Mazroui, S. Di Marco, E. Clair, C. von Roretz, S. A. Tenenbaum, J. D. Keene, M. Saleh, and I.-E. Gallouzi
Caspase-mediated cleavage of HuR in the cytoplasm contributes to pp32/PHAP-I regulation of apoptosis
J. Cell Biol., January 10, 2008; 180(1): 113 - 127.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
E. J. Fialcowitz-White, B. Y. Brewer, J. D. Ballin, C. D. Willis, E. A. Toth, and G. M. Wilson
Specific Protein Domains Mediate Cooperative Assembly of HuR Oligomers on AU-rich mRNA-destabilizing Sequences
J. Biol. Chem., July 20, 2007; 282(29): 20948 - 20959.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Biol. CellHome page
A. Doller, A. Huwiler, R. Muller, H. H. Radeke, J. Pfeilschifter, and W. Eberhardt
Protein Kinase C{alpha}-dependent Phosphorylation of the mRNA-stabilizing Factor HuR: Implications for Posttranscriptional Regulation of Cyclooxygenase-2
Mol. Biol. Cell, June 1, 2007; 18(6): 2137 - 2148.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
T. O. Yarovinsky, N. S. Butler, M. M. Monick, and G. W. Hunninghake
Early Exposure to IL-4 Stabilizes IL-4 mRNA in CD4+ T Cells via RNA-Binding Protein HuR
J. Immunol., October 1, 2006; 177(7): 4426 - 4435.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. T. Prechtel, J. Chemnitz, S. Schirmer, C. Ehlers, I. Langbein-Detsch, J. Stulke, M.-C. Dabauvalle, R. H. Kehlenbach, and J. Hauber
Expression of CD83 Is Regulated by HuR via a Novel cis-Active Coding Region RNA Element
J. Biol. Chem., April 21, 2006; 281(16): 10912 - 10925.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. Jeyaraj, D. Dakhlallah, S. R. Hill, and B. S. Lee
HuR Stabilizes Vacuolar H+-translocating ATPase mRNA during Cellular Energy Depletion
J. Biol. Chem., November 11, 2005; 280(45): 37957 - 37964.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
S. Di Marco, R. Mazroui, P. Dallaire, S. Chittur, S. A. Tenenbaum, D. Radzioch, A. Marette, and I.-E. Gallouzi
NF-{kappa}B-Mediated MyoD Decay during Muscle Wasting Requires Nitric Oxide Synthase mRNA Stabilization, HuR Protein, and Nitric Oxide Release
Mol. Cell. Biol., August 1, 2005; 25(15): 6533 - 6545.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
R. Pullmann Jr., M. Juhaszova, I. L. de Silanes, T. Kawai, K. Mazan-Mamczarz, M. K. Halushka, and M. Gorospe
Enhanced Proliferation of Cultured Human Vascular Smooth Muscle Cells Linked to Increased Function of RNA-binding Protein HuR
J. Biol. Chem., June 17, 2005; 280(24): 22819 - 22826.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
M. Heinonen, P. Bono, K. Narko, S.-H. Chang, J. Lundin, H. Joensuu, H. Furneaux, T. Hla, C. Haglund, and A. Ristimaki
Cytoplasmic HuR Expression Is a Prognostic Factor in Invasive Ductal Breast Carcinoma
Cancer Res., March 15, 2005; 65(6): 2157 - 2161.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 2004 by the American Society for Biochemistry and Molecular Biology.