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 Majumder, M.
Right arrow Articles by Ray, R. B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Majumder, M.
Right arrow Articles by Ray, R. B.

 Previous Article  |  Next Article 

Journal of Virology, February 2001, p. 1401-1407, Vol. 75, No. 3
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.3.1401-1407.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Hepatitis C Virus NS5A Physically Associates with p53 and Regulates p21/waf1 Gene Expression in a p53-Dependent Manner

Mainak Majumder,1 Asish K. Ghosh,1 Robert Steele,1 Ranjit Ray,2,3 and Ratna B. Ray1,2,*

Department of Pathology,1 Division of Infectious Diseases and Immunology,2 and Department of Molecular Microbiology and Immunology,3 Saint Louis University, St. Louis, Missouri 63104

Received 25 April 2000/Accepted 6 November 2000

We have previously demonstrated that hepatitis C virus (HCV) NS5A protein promotes cell growth and transcriptionally regulates the p21/waf1 promoter, a downstream effector gene of p53. In this study, we investigated the molecular mechanism of NS5A-mediated transcriptional repression of p21/waf1. We observed that transcriptional repression of the p21/waf1 gene by NS5A is p53 dependent by using p53 wild-type (+/+) and null (-/-) cells. Interestingly, p53-mediated transcriptional activation from a synthetic promoter containing multiple p53 binding sites (PG13-LUC) was abrogated following expression of HCV NS5A. Additional studies using pull-down experiments, in vivo coimmunoprecipitation, and mammalian two-hybrid assays demonstrated that NS5A physically associates with p53. Confocal microscopy revealed sequestration of p53 in the perinuclear membrane and colocalization with NS5A in transfected HepG2 and Saos-2 cells. Together these results suggest that an association of NS5A and p53 allows transcriptional modulation of the p21/waf1 gene and may contribute to HCV-mediated pathogenesis.

* Corresponding author. Mailing address: Department of Pathology, Saint Louis University, 1402 S. Grand Blvd., 4th Floor, St. Louis, MO 63104. Phone: (314) 577-8331. Fax: (314) 771-3816. E-mail: rayrb{at}slu.edu.

Journal of Virology, February 2001, p. 1401-1407, Vol. 75, No. 3
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.3.1401-1407.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • McGivern, D. R., Villanueva, R. A., Chinnaswamy, S., Kao, C. C., Lemon, S. M. (2009). Impaired Replication of Hepatitis C Virus Containing Mutations in a Conserved NS5B Retinoblastoma Protein-Binding Motif. J. Virol. 83: 7422-7433 [Abstract] [Full Text]  
  • Raychaudhuri, S., Fontanes, V., Barat, B., Dasgupta, A. (2009). Activation of Ribosomal RNA Transcription by Hepatitis C Virus Involves Upstream Binding Factor Phosphorylation via Induction of Cyclin D1. Cancer Res. 69: 2057-2064 [Abstract] [Full Text]  
  • Kanda, T., Steele, R., Ray, R., Ray, R. B. (2008). Hepatitis C Virus Core Protein Augments Androgen Receptor-Mediated Signaling. J. Virol. 82: 11066-11072 [Abstract] [Full Text]  
  • Tran, G. (2008). The role of hepatitis C virus in the pathogenesis of hepatocellular carcinoma. Bioscience Horizons 1: 167-175 [Abstract] [Full Text]  
  • Inubushi, S., Nagano-Fujii, M., Kitayama, K., Tanaka, M., An, C., Yokozaki, H., Yamamura, H., Nuriya, H., Kohara, M., Sada, K., Hotta, H. (2008). Hepatitis C virus NS5A protein interacts with and negatively regulates the non-receptor protein tyrosine kinase Syk. J. Gen. Virol. 89: 1231-1242 [Abstract] [Full Text]  
  • Taguwa, S., Okamoto, T., Abe, T., Mori, Y., Suzuki, T., Moriishi, K., Matsuura, Y. (2008). Human Butyrate-Induced Transcript 1 Interacts with Hepatitis C Virus NS5A and Regulates Viral Replication. J. Virol. 82: 2631-2641 [Abstract] [Full Text]  
  • Chen, Y.-W., Klimstra, D. S., Mongeau, M. E., Tatem, J. L., Boyartchuk, V., Lewis, B. C. (2007). Loss of p53 and Ink4a/Arf Cooperate in a Cell Autonomous Fashion to Induce Metastasis of Hepatocellular Carcinoma Cells. Cancer Res. 67: 7589-7596 [Abstract] [Full Text]  
  • Kalamvoki, M., Georgopoulou, U., Mavromara, P. (2006). The NS5A Protein of the Hepatitis C Virus Genotype 1a Is Cleaved by Caspases to Produce C-terminal-truncated Forms of the Protein That Reside Mainly in the Cytosol. J. Biol. Chem. 281: 13449-13462 [Abstract] [Full Text]  
  • Farazi, P. A., Glickman, J., Horner, J., DePinho, R. A. (2006). Cooperative Interactions of p53 Mutation, Telomere Dysfunction, and Chronic Liver Damage in Hepatocellular Carcinoma Progression.. Cancer Res. 66: 4766-4773 [Abstract] [Full Text]  
  • Choi, S.-H., Hwang, S. B. (2006). Modulation of the Transforming Growth Factor-beta Signal Transduction Pathway by Hepatitis C Virus Nonstructural 5A Protein. J. Biol. Chem. 281: 7468-7478 [Abstract] [Full Text]  
  • Hamamoto, I., Nishimura, Y., Okamoto, T., Aizaki, H., Liu, M., Mori, Y., Abe, T., Suzuki, T., Lai, M. M. C., Miyamura, T., Moriishi, K., Matsuura, Y. (2005). Human VAP-B Is Involved in Hepatitis C Virus Replication through Interaction with NS5A and NS5B. J. Virol. 79: 13473-13482 [Abstract] [Full Text]  
  • Gartel, A. L., Radhakrishnan, S. K. (2005). Lost in Transcription: p21 Repression, Mechanisms, and Consequences. Cancer Res. 65: 3980-3985 [Abstract] [Full Text]  
  • Pfeiffer, J. K., Kirkegaard, K. (2005). Ribavirin Resistance in Hepatitis C Virus Replicon-Containing Cell Lines Conferred by Changes in the Cell Line or Mutations in the Replicon RNA. J. Virol. 79: 2346-2355 [Abstract] [Full Text]  
  • Appel, N., Herian, U., Bartenschlager, R. (2005). Efficient Rescue of Hepatitis C Virus RNA Replication by trans-Complementation with Nonstructural Protein 5A. J. Virol. 79: 896-909 [Abstract] [Full Text]  
  • Simmonds, P. (2004). Genetic diversity and evolution of hepatitis C virus - 15 years on. J. Gen. Virol. 85: 3173-3188 [Abstract] [Full Text]  
  • Kalamvoki, M., Mavromara, P. (2004). Calcium-Dependent Calpain Proteases Are Implicated in Processing of the Hepatitis C Virus NS5A Protein. J. Virol. 78: 11865-11878 [Abstract] [Full Text]  
  • Macdonald, A., Harris, M. (2004). Hepatitis C virus NS5A: tales of a promiscuous protein. J. Gen. Virol. 85: 2485-2502 [Abstract] [Full Text]  
  • Evans, M. J., Rice, C. M., Goff, S. P. (2004). Phosphorylation of hepatitis C virus nonstructural protein 5A modulates its protein interactions and viral RNA replication. Proc. Natl. Acad. Sci. USA 101: 13038-13043 [Abstract] [Full Text]  
  • Graziani, R., Paonessa, G. (2004). Dominant negative effect of wild-type NS5A on NS5A-adapted subgenomic hepatitis C virus RNA replicon. J. Gen. Virol. 85: 1867-1875 [Abstract] [Full Text]  
  • Yamada, T., Hiraoka, Y., Ikehata, M., Kimbara, K., Avner, B. S., Das Gupta, T. K., Chakrabarty, A. M. (2004). Apoptosis or growth arrest: Modulation of tumor suppressor p53's specificity by bacterial redox protein azurin. Proc. Natl. Acad. Sci. USA 101: 4770-4775 [Abstract] [Full Text]  
  • Shimakami, T., Hijikata, M., Luo, H., Ma, Y. Y., Kaneko, S., Shimotohno, K., Murakami, S. (2004). Effect of Interaction between Hepatitis C Virus NS5A and NS5B on Hepatitis C Virus RNA Replication with the Hepatitis C Virus Replicon. J. Virol. 78: 2738-2748 [Abstract] [Full Text]  
  • Macdonald, A., Crowder, K., Street, A., McCormick, C., Harris, M. (2004). The hepatitis C virus NS5A protein binds to members of the Src family of tyrosine kinases and regulates kinase activity. J. Gen. Virol. 85: 721-729 [Abstract] [Full Text]  
  • Scholle, F., Li, K., Bodola, F., Ikeda, M., Luxon, B. A., Lemon, S. M. (2004). Virus-Host Cell Interactions during Hepatitis C Virus RNA Replication: Impact of Polyprotein Expression on the Cellular Transcriptome and Cell Cycle Association with Viral RNA Synthesis. J. Virol. 78: 1513-1524 [Abstract] [Full Text]  
  • Waris, G., Livolsi, A., Imbert, V., Peyron, J.-F., Siddiqui, A. (2003). Hepatitis C Virus NS5A and Subgenomic Replicon Activate NF-{kappa}B via Tyrosine Phosphorylation of I{kappa}B{alpha} and Its Degradation by Calpain Protease. J. Biol. Chem. 278: 40778-40787 [Abstract] [Full Text]  
  • Ghosh, A. K., Steele, R., Ray, R. B. (2003). Modulation of Human Luteinizing Hormone {beta} Gene Transcription by MIP-2A. J. Biol. Chem. 278: 24033-24038 [Abstract] [Full Text]  
  • Geiss, G. K., Carter, V. S., He, Y., Kwieciszewski, B. K., Holzman, T., Korth, M. J., Lazaro, C. A., Fausto, N., Bumgarner, R. E., Katze, M. G. (2003). Gene Expression Profiling of the Cellular Transcriptional Network Regulated by Alpha/Beta Interferon and Its Partial Attenuation by the Hepatitis C Virus Nonstructural 5A Protein. J. Virol. 77: 6367-6375 [Abstract] [Full Text]  
  • Zech, B., Kurtenbach, A., Krieger, N., Strand, D., Blencke, S., Morbitzer, M., Salassidis, K., Cotten, M., Wissing, J., Obert, S., Bartenschlager, R., Herget, T., Daub, H. (2003). Identification and characterization of amphiphysin II as a novel cellular interaction partner of the hepatitis C virus NS5A protein. J. Gen. Virol. 84: 555-560 [Abstract] [Full Text]  
  • Brass, V., Bieck, E., Montserret, R., Wolk, B., Hellings, J. A., Blum, H. E., Penin, F., Moradpour, D. (2002). An Amino-terminal Amphipathic alpha -Helix Mediates Membrane Association of the Hepatitis C Virus Nonstructural Protein 5A. J. Biol. Chem. 277: 8130-8139 [Abstract] [Full Text]  
  • Gong, G., Waris, G., Tanveer, R., Siddiqui, A. (2001). Human hepatitis C virus NS5A protein alters intracellular calcium levels, induces oxidative stress, and activates STAT-3 and NF-kappa B. Proc. Natl. Acad. Sci. USA 10.1073/pnas.171311298v1 [Abstract] [Full Text]  
  • Gong, G., Waris, G., Tanveer, R., Siddiqui, A. (2001). Human hepatitis C virus NS5A protein alters intracellular calcium levels, induces oxidative stress, and activates STAT-3 and NF-kappa B. Proc. Natl. Acad. Sci. USA 98: 9599-9604 [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»