This Article
Right arrow Full Text
Right arrow Full Text (PDF)
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 Tran, H.
Right arrow Articles by Nagamine, Y.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tran, H.
Right arrow Articles by Nagamine, Y.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, October 2003, p. 7177-7188, Vol. 23, No. 20
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.20.7177-7188.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Stabilization of Urokinase and Urokinase Receptor mRNAs by HuR Is Linked to Its Cytoplasmic Accumulation Induced by Activated Mitogen-Activated Protein Kinase-Activated Protein Kinase 2

Hoanh Tran, Fabienne Maurer,{dagger} and Yoshikuni Nagamine*

Friedrich Miescher Institute for Biomedical Research, Novartis Research Foundation, CH-4058 Basel, Switzerland

Received 12 June 2003/ Accepted 8 July 2003

The mRNAs of urokinase plasminogen activator (uPA) and its receptor, uPAR, contain instability-determining AU-rich elements (AREs) in their 3' untranslated regions. The cellular proteins binding to these RNA sequences (AREuPA/uPAR) are not known. We show here that the mRNA-stabilizing factor HuR functionally interacts with these sequences. HuR stabilized an AREuPA-containing RNA substrate in vitro and stabilized in HeLa Tet-off cells both endogenous uPA and uPAR mRNAs and a ß-globin reporter mRNA containing the AREuPA. RNAi-mediated depletion of HuR in BT-549 and MDA-MB-231 cells significantly reduced the steady-state levels of endogenous uPA and uPAR mRNAs. Furthermore, we show that a constitutively active form of mitogen-activated protein kinase-activated protein kinase 2 (MK2), MK2-EE, has an ARE-mRNA-stabilizing effect that correlates with its ability to enhance the cytoplasmic accumulation of endogenous HuR, but not in cells cotransfected with a dominant negative version of MK2, MK2-K76R. These effects were mimicked by hydrogen peroxide treatment (oxidative stress), which resulted in the phosphorylation of endogenous MK2. In addition, hydrogen peroxide treatment enhanced the cytoplasmic binding of HuR to the AREuPA, which was abrogated in cells transfected with MK2-K76R. These results indicate a role for HuR and MK2 in regulating the expression of uPA and uPAR genes at the posttranscriptional level.

* Corresponding author. Mailing address: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland. Phone: 41 61 697 6669. Fax: 41 61 697 3976. E-mail: Yoshikuni.Nagamine{at}fmi.ch.

{dagger} Present address: Division of Medical Genetics, CHUV University Hospital, CH-1011 Lausanne, Switzerland.

Molecular and Cellular Biology, October 2003, p. 7177-7188, Vol. 23, No. 20
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.20.7177-7188.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Al-Ahmadi, W., Al-Ghamdi, M., Al-Haj, L., Al-Saif, M., Khabar, K. S. A. (2009). Alternative polyadenylation variants of the RNA binding protein, HuR: abundance, role of AU-rich elements and auto-Regulation. Nucleic Acids Res 37: 3612-3624 [Abstract] [Full Text]  
  • Shetty, S., Padijnayayveetil, J., Tucker, T., Stankowska, D., Idell, S. (2008). The fibrinolytic system and the regulation of lung epithelial cell proteolysis, signaling, and cellular viability. Am. J. Physiol. Lung Cell. Mol. Physiol. 295: L967-L975 [Abstract] [Full Text]  
  • Wang, S., Zhang, J., Zhang, Y., Kern, S., Danner, R. L. (2008). Nitric oxide-p38 MAPK signaling stabilizes mRNA through AU-rich element-dependent and -independent mechanisms. J. Leukoc. Biol. 83: 982-990 [Abstract] [Full Text]  
  • Quann, E. J., Khwaja, F., Djakiew, D. (2007). The p38 MAPK Pathway Mediates Aryl Propionic Acid Induced Messenger RNA Stability of p75NTR in Prostate Cancer Cells. Cancer Res. 67: 11402-11410 [Abstract] [Full Text]  
  • Heinonen, M., Fagerholm, R., Aaltonen, K., Kilpivaara, O., Aittomaki, K., Blomqvist, C., Heikkila, P., Haglund, C., Nevanlinna, H., Ristimaki, A. (2007). Prognostic Role of HuR in Hereditary Breast Cancer. Clin. Cancer Res. 13: 6959-6963 [Abstract] [Full Text]  
  • To, K., Zhao, Y., Jiang, H., Hu, K., Wang, M., Wu, J., Lee, C., Yokom, D. W., Stratford, A. L., Klinge, U., Mertens, P. R., Chen, C. S., Bally, M., Yapp, D., Dunn, S. E. (2007). The Phosphoinositide-Dependent Kinase-1 Inhibitor 2-Amino-N-[4-[5-(2-phenanthrenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]phenyl]-acetamide (OSU-03012) Prevents Y-Box Binding Protein-1 from Inducing Epidermal Growth Factor Receptor. Mol. Pharmacol. 72: 641-652 [Abstract] [Full Text]  
  • Khabar, K. S. A. (2007). Rapid transit in the immune cells: the role of mRNA turnover regulation. J. Leukoc. Biol. 81: 1335-1344 [Abstract] [Full Text]  
  • Begin, P., Tremblay, K., Daley, D., Lemire, M., Claveau, S., Salesse, C., Kacel, S., Montpetit, A., Becker, A., Chan-Yeung, M., Kozyrskyj, A. L., Hudson, T. J., Laprise, C. (2007). Association of Urokinase-type Plasminogen Activator with Asthma and Atopy. Am. J. Respir. Crit. Care Med. 175: 1109-1116 [Abstract] [Full Text]  
  • Zou, T., Mazan-Mamczarz, K., Rao, J. N., Liu, L., Marasa, B. S., Zhang, A.-H., Xiao, L., Pullmann, R., Gorospe, M., Wang, J.-Y. (2006). Polyamine Depletion Increases Cytoplasmic Levels of RNA-binding Protein HuR Leading to Stabilization of Nucleophosmin and p53 mRNAs. J. Biol. Chem. 281: 19387-19394 [Abstract] [Full Text]  
  • Fritz, D. T., Jiang, S., Xu, J., Rogers, M. B. (2006). A Polymorphism in a Conserved Posttranscriptional Regulatory Motif Alters Bone Morphogenetic Protein 2 (BMP2) RNA:Protein Interactions. Mol. Endocrinol. 20: 1574-1586 [Abstract] [Full Text]  
  • Prechtel, A. T., Chemnitz, J., Schirmer, S., Ehlers, C., Langbein-Detsch, I., Stulke, J., Dabauvalle, M.-C., Kehlenbach, R. H., Hauber, J. (2006). Expression of CD83 Is Regulated by HuR via a Novel cis-Active Coding Region RNA Element. J. Biol. Chem. 281: 10912-10925 [Abstract] [Full Text]  
  • Fan, J., Heller, N. M., Gorospe, M., Atasoy, U., Stellato, C. (2005). The role of post-transcriptional regulation in chemokine gene expression in inflammation and allergy. Eur Respir J 26: 933-947 [Abstract] [Full Text]  
  • Song, I.-S., Tatebe, S., Dai, W., Kuo, M. T. (2005). Delayed Mechanism for Induction of {gamma}-Glutamylcysteine Synthetase Heavy Subunit mRNA Stability by Oxidative Stress Involving p38 Mitogen-activated Protein Kinase Signaling. J. Biol. Chem. 280: 28230-28240 [Abstract] [Full Text]  
  • Gringhuis, S. I., Garcia-Vallejo, J. J., van het Hof, B., van Dijk, W. (2005). Convergent Actions of I{kappa}B Kinase {beta} and Protein Kinase C{delta} Modulate mRNA Stability through Phosphorylation of 14-3-3{beta} Complexed with Tristetraprolin. Mol. Cell. Biol. 25: 6454-6463 [Abstract] [Full Text]  
  • Bonafe, N., Gilmore-Hebert, M., Folk, N. L., Azodi, M., Zhou, Y., Chambers, S. K. (2005). Glyceraldehyde-3-Phosphate Dehydrogenase Binds to the AU-Rich 3' Untranslated Region of Colony-Stimulating Factor-1 (CSF-1) Messenger RNA in Human Ovarian Cancer Cells: Possible Role in CSF-1 Posttranscriptional Regulation and Tumor Phenotype. Cancer Res. 65: 3762-3771 [Abstract] [Full Text]  
  • Iyer, V., Pumiglia, K., DiPersio, C. M. (2005). {alpha}3{beta}1 integrin regulates MMP-9 mRNA stability in immortalized keratinocytes: a novel mechanism of integrin-mediated MMP gene expression. J. Cell Sci. 118: 1185-1195 [Abstract] [Full Text]  
  • Yang, X., Wang, W., Fan, J., Lal, A., Yang, D., Cheng, H., Gorospe, M. (2004). Prostaglandin A2-mediated Stabilization of p21 mRNA through an ERK-dependent Pathway Requiring the RNA-binding Protein HuR. J. Biol. Chem. 279: 49298-49306 [Abstract] [Full Text]  
  • Denkert, C., Weichert, W., Winzer, K.-J., Muller, B.-M., Noske, A., Niesporek, S., Kristiansen, G., Guski, H., Dietel, M., Hauptmann, S. (2004). Expression of the ELAV-Like Protein HuR Is Associated with Higher Tumor Grade and Increased Cyclooxygenase-2 Expression in Human Breast Carcinoma. Clin. Cancer Res. 10: 5580-5586 [Abstract] [Full Text]  
  • Onesto, C., Berra, E., Grepin, R., Pages, G. (2004). Poly(A)-binding Protein-interacting Protein 2, a Strong Regulator of Vascular Endothelial Growth Factor mRNA. J. Biol. Chem. 279: 34217-34226 [Abstract] [Full Text]  
  • Winzen, R., Gowrishankar, G., Bollig, F., Redich, N., Resch, K., Holtmann, H. (2004). Distinct Domains of AU-Rich Elements Exert Different Functions in mRNA Destabilization and Stabilization by p38 Mitogen-Activated Protein Kinase or HuR. Mol. Cell. Biol. 24: 4835-4847 [Abstract] [Full Text]  
  • CHEN, C.-Y. A., XU, N., ZHU, W., SHYU, A.-B. (2004). Functional dissection of hnRNP D suggests that nuclear import is required before hnRNP D can modulate mRNA turnover in the cytoplasm. RNA 10: 669-680 [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»