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 Galbán, S.
Right arrow Articles by Gorospe, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Galbán, S.
Right arrow Articles by Gorospe, M.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, April 2003, p. 2316-2328, Vol. 23, No. 7
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.7.2316-2328.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

von Hippel-Lindau Protein-Mediated Repression of Tumor Necrosis Factor Alpha Translation Revealed through Use of cDNA Arrays

Stefanie Galbán,1 Jinshui Fan,1 Jennifer L. Martindale,1 Chris Cheadle,2 Bryan Hoffman,3 Michael P. Woods,3 Gretchen Temeles,3 Jürgen Brieger,4 Jochen Decker,5 and Myriam Gorospe1*

Laboratory of Cellular and Molecular Biology,1 DNA Array Unit, National Institute on Aging Intramural Research Program, National Institutes of Health, Baltimore, Maryland 21224,2 Message Pharmaceuticals, Inc., Malvern, Pennsylvania 19355,3 Department of Otorhinolaryngology, School of Medicine, Johannes Gutenberg University, 55101 Mainz,4 Bioscientia Institute, 55128 Ingelheim, Germany5

Received 30 October 2002/ Returned for modification 10 December 2002/ Accepted 10 January 2003

Based on evidence that the von Hippel-Lindau (VHL) tumor suppressor protein is associated with polysomes and interacts with translation regulatory factors, we set out to investigate the potential influence of pVHL on protein translation. To this end, renal cell carcinoma (RCC) cells that either lacked pVHL or expressed pVHL through stable transfection were used to prepare RNA from cytosolic (unbound) and polysome-bound fractions. Hybridization of cDNA arrays using RNA from each fraction revealed a subset of transcripts whose abundance in polysomes decreased when pVHL function was restored. The tumor necrosis factor alpha (TNF-{alpha}) mRNA was identified as one of the transcripts that preferentially associated with polysomes in pVHL-deficient cells. Additional evidence that the TNF-{alpha} mRNA was a target of translational repression by pVHL was obtained from reporter gene assays, which further revealed that pVHL's inhibitory influence on protein synthesis occurred through the TNF-{alpha} 3'-untranslated region. Our findings uncover a novel function for the pVHL tumor suppressor protein as regulator of protein translation.

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

Molecular and Cellular Biology, April 2003, p. 2316-2328, Vol. 23, No. 7
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.7.2316-2328.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Hervouet, E., Cizkova, A., Demont, J., Vojtiskova, A., Pecina, P., Franssen-van Hal, N. L.W., Keijer, J., Simonnet, H., Ivanek, R., Kmoch, S., Godinot, C., Houstek, J. (2008). HIF and reactive oxygen species regulate oxidative phosphorylation in cancer. Carcinogenesis 29: 1528-1537 [Abstract] [Full Text]  
  • Das, T., Sa, G., Hilston, C., Kudo, D., Rayman, P., Biswas, K., Molto, L., Bukowski, R., Rini, B., Finke, J. H., Tannenbaum, C. (2008). GM1 and Tumor Necrosis Factor-{alpha}, Overexpressed in Renal Cell Carcinoma, Synergize to Induce T-Cell Apoptosis. Cancer Res. 68: 2014-2023 [Abstract] [Full Text]  
  • Raval, G., Biswas, S., Rayman, P., Biswas, K., Sa, G., Ghosh, S., Thornton, M., Hilston, C., Das, T., Bukowski, R., Finke, J., Tannenbaum, C. S. (2007). TNF-{alpha} Induction of GM2 Expression on Renal Cell Carcinomas Promotes T Cell Dysfunction. J. Immunol. 178: 6642-6652 [Abstract] [Full Text]  
  • Rastaldi, M. P. (2007). Necrotizing crescentic glomerulonephritis--a conditional knockout model discloses new therapeutic challenges. Nephrol Dial Transplant 22: 1020-1022 [Full Text]  
  • Kulbe, H., Thompson, R., Wilson, J. L., Robinson, S., Hagemann, T., Fatah, R., Gould, D., Ayhan, A., Balkwill, F. (2007). The Inflammatory Cytokine Tumor Necrosis Factor-{alpha} Generates an Autocrine Tumor-Promoting Network in Epithelial Ovarian Cancer Cells. Cancer Res. 67: 585-592 [Abstract] [Full Text]  
  • Blais, J. D., Addison, C. L., Edge, R., Falls, T., Zhao, H., Wary, K., Koumenis, C., Harding, H. P., Ron, D., Holcik, M., Bell, J. C. (2006). Perk-Dependent Translational Regulation Promotes Tumor Cell Adaptation and Angiogenesis in Response to Hypoxic Stress. Mol. Cell. Biol. 26: 9517-9532 [Abstract] [Full Text]  
  • Baird, S. D., Turcotte, M., Korneluk, R. G., Holcik, M. (2006). Searching for IRES. RNA 12: 1755-1785 [Abstract] [Full Text]  
  • Reinert, L. S., Shi, B., Nandi, S., Mazan-Mamczarz, K., Vitolo, M., Bachman, K. E., He, H., Gartenhaus, R. B. (2006). MCT-1 Protein Interacts with the Cap Complex and Modulates Messenger RNA Translational Profiles.. Cancer Res. 66: 8994-9001 [Abstract] [Full Text]  
  • Koumenis, C., Wouters, B. G. (2006). "Translating" Tumor Hypoxia: Unfolded Protein Response (UPR)-Dependent and UPR-Independent Pathways. Mol Cancer Res 4: 423-436 [Abstract] [Full Text]  
  • Kawai, T., Lal, A., Yang, X., Galban, S., Mazan-Mamczarz, K., Gorospe, M. (2006). Translational Control of Cytochrome c by RNA-Binding Proteins TIA-1 and HuR. Mol. Cell. Biol. 26: 3295-3307 [Abstract] [Full Text]  
  • Szlosarek, P. W., Grimshaw, M. J., Kulbe, H., Wilson, J. L., Wilbanks, G. D., Burke, F., Balkwill, F. R. (2006). Expression and regulation of tumor necrosis factor {alpha} in normal and malignant ovarian epithelium.. Molecular Cancer Therapeutics 5: 382-390 [Abstract] [Full Text]  
  • Lu, X., de la Pena, L., Barker, C., Camphausen, K., Tofilon, P. J. (2006). Radiation-Induced Changes in Gene Expression Involve Recruitment of Existing Messenger RNAs to and away from Polysomes. Cancer Res. 66: 1052-1061 [Abstract] [Full Text]  
  • STEFANI, G., SLACK, F. (2006). MicroRNAs in Search of a Target. Cold Spring Harb Symp Quant Biol 71: 129-134 [Abstract]  
  • Kulbe, H., Hagemann, T., Szlosarek, P. W., Balkwill, F. R., Wilson, J. L. (2005). The Inflammatory Cytokine Tumor Necrosis Factor-{alpha} Regulates Chemokine Receptor Expression on Ovarian Cancer Cells. Cancer Res. 65: 10355-10362 [Abstract] [Full Text]  
  • Hervouet, E., Demont, J., Pecina, P., Vojtiskova, A., Houstek, J., Simonnet, H., Godinot, C. (2005). A new role for the von Hippel-Lindau tumor suppressor protein: stimulation of mitochondrial oxidative phosphorylation complex biogenesis. Carcinogenesis 26: 531-539 [Abstract] [Full Text]  
  • Biju, M. P., Neumann, A. K., Bensinger, S. J., Johnson, R. S., Turka, L. A., Haase, V. H. (2004). Vhlh Gene Deletion Induces Hif-1-Mediated Cell Death in Thymocytes. Mol. Cell. Biol. 24: 9038-9047 [Abstract] [Full Text]  
  • Tan, M.-H., Rogers, C. G., Cooper, J. T., Ditlev, J. A., Maatman, T. J., Yang, X., Furge, K. A., Teh, B. T. (2004). Gene Expression Profiling of Renal Cell Carcinoma. Clin. Cancer Res. 10: 6315S-6321S [Abstract] [Full Text]  
  • Blais, J. D., Filipenko, V., Bi, M., Harding, H. P., Ron, D., Koumenis, C., Wouters, B. G., Bell, J. C. (2004). Activating Transcription Factor 4 Is Translationally Regulated by Hypoxic Stress. Mol. Cell. Biol. 24: 7469-7482 [Abstract] [Full Text]  
  • Wang, Y., Ringquist, S., Cho, A. H., Rondeau, G., Welsh, J. (2004). High-throughput polyribosome fractionation. Nucleic Acids Res 32: e79-e79 [Abstract] [Full Text]  
  • de Silanes, I. L., Zhan, M., Lal, A., Yang, X., Gorospe, M. (2004). Identification of a target RNA motif for RNA-binding protein HuR. Proc. Natl. Acad. Sci. USA 101: 2987-2992 [Abstract] [Full Text]  
  • Galban, S., Martindale, J. L., Mazan-Mamczarz, K., Lopez de Silanes, I., Fan, J., Wang, W., Decker, J., Gorospe, M. (2003). Influence of the RNA-Binding Protein HuR in pVHL-Regulated p53 Expression in Renal Carcinoma Cells. Mol. Cell. Biol. 23: 7083-7095 [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»