This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental material
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
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 arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kuwano, Y.
Right arrow Articles by Gorospe, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kuwano, Y.
Right arrow Articles by Gorospe, M.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, July 2008, p. 4562-4575, Vol. 28, No. 14
0270-7306/08/$08.00+0     doi:10.1128/MCB.00165-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

MKP-1 mRNA Stabilization and Translational Control by RNA-Binding Proteins HuR and NF90{triangledown} ,{dagger}

Yuki Kuwano, Hyeon Ho Kim, Kotb Abdelmohsen, Rudolf Pullmann Jr., Jennifer L. Martindale, Xiaoling Yang, and Myriam Gorospe*

Laboratory of Cellular and Molecular Biology, National Institute on Aging-Intramural Research Program, National Institutes of Health, Baltimore, Maryland 21228

Received 1 February 2008/ Returned for modification 5 March 2008/ Accepted 7 May 2008

The mitogen-activated protein (MAP) kinase phosphatase 1 (MKP-1) plays a major role in dephosphorylating and thereby inactivating the MAP kinases extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38. Here, we examine the posttranscriptional events underlying the robust MKP-1 induction by oxidants in HeLa cells. H2O2 treatment potently stabilized the MKP-1 mRNA and increased the association of MKP-1 mRNA with the translation machinery. Four RNA-binding proteins (RNA-BPs) that influence mRNA turnover and/or translation (HuR, NF90, TIAR, and TIA-1) were found to bind to biotinylated transcripts spanning the MKP-1 AU-rich 3' untranslated region. By using ribonucleoprotein immunoprecipitation analysis, we showed that H2O2 treatment increased the association of MKP-1 mRNA with HuR and NF90 and decreased its association with the translational repressors TIAR and TIA-1. HuR or NF90 silencing significantly diminished the H2O2-stimulated MKP-1 mRNA stability; HuR silencing also markedly decreased MKP-1 translation. In turn, lowering MKP-1 expression in HuR-silenced cultures resulted in substantially elevated phosphorylation of JNK and p38 after H2O2 treatment. Collectively, MKP-1 upregulation by oxidative stress is potently influenced by increased mRNA stability and translation, mediated at least in part by the RNA-BPs HuR and NF90.

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

{triangledown} Published ahead of print on 19 May 2008.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

Molecular and Cellular Biology, July 2008, p. 4562-4575, Vol. 28, No. 14
0270-7306/08/$08.00+0     doi:10.1128/MCB.00165-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Kuwano, Y., Pullmann, R. Jr., Marasa, B. S., Abdelmohsen, K., Lee, E. K., Yang, X., Martindale, J. L., Zhan, M., Gorospe, M. (2009). NF90 selectively represses the translation of target mRNAs bearing an AU-rich signature motif. Nucleic Acids Res 0: gkp861v1-gkp861 [Abstract] [Full Text]  
  • Yang, D., Xie, P., Guo, S., Li, H. (2009). Induction of MAPK phosphatase-1 by hypothermia inhibits TNF-{alpha}-induced endothelial barrier dysfunction and apoptosis. Cardiovasc Res 0: cvp323v2-cvp323 [Abstract] [Full Text]  
  • Zhang, X., Zou, T., Rao, J. N., Liu, L., Xiao, L., Wang, P.-Y., Cui, Y.-H., Gorospe, M., Wang, J.-Y. (2009). Stabilization of XIAP mRNA through the RNA binding protein HuR regulated by cellular polyamines. Nucleic Acids Res 0: gkp755v1-gkp755 [Abstract] [Full Text]  
  • Costantino, C. L., Witkiewicz, A. K., Kuwano, Y., Cozzitorto, J. A., Kennedy, E. P., Dasgupta, A., Keen, J. C., Yeo, C. J., Gorospe, M., Brody, J. R. (2009). The Role of HuR in Gemcitabine Efficacy in Pancreatic Cancer: HuR Up-regulates the Expression of the Gemcitabine Metabolizing Enzyme Deoxycytidine Kinase. Cancer Res. 69: 4567-4572 [Abstract] [Full Text]  
  • Kuwano, Y., Rabinovic, A., Srikantan, S., Gorospe, M., Demple, B. (2009). Analysis of Nitric Oxide-Stabilized mRNAs in Human Fibroblasts Reveals HuR-Dependent Heme Oxygenase 1 Upregulation. Mol. Cell. Biol. 29: 2622-2635 [Abstract] [Full Text]  
  • Lopez de Silanes, I., Gorospe, M., Taniguchi, H., Abdelmohsen, K., Srikantan, S., Alaminos, M., Berdasco, M., Urdinguio, R. G., Fraga, M. F., Jacinto, F. V., Esteller, M. (2009). The RNA-binding protein HuR regulates DNA methylation through stabilization of DNMT3b mRNA. Nucleic Acids Res 37: 2658-2671 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»