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 Becker, S. A.
Right arrow Articles by Slagle, B. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Becker, S. A.
Right arrow Articles by Slagle, B. L.

 Previous Article  |  Next Article 

J. Virol., Jan 1998, 266-272, Vol 72, No. 1
Copyright © 1998, American Society for Microbiology

Hepatitis B virus X protein interferes with cellular DNA repair

SA Becker, TH Lee, JS Butel and BL Slagle
Division of Molecular Virology, Baylor College of Medicine, Houston, Texas 77030, USA.

The hepatitis B virus X protein (HBx) is a broadly acting transactivator implicated in the development of liver cancer. Recently, HBx has been reported to interact with several different cellular proteins, including our report of its binding to XAP-1, the human homolog of the simian repair protein UVDDB. In the present study, several HBx mutants were used to localize the minimal domain of HBx required for binding to XAP-1/UVDDB to amino acids 55 to 101. The normal function of XAP-1/UVDDB is thought to involve binding to damaged DNA, the first step in nucleotide excision repair (NER); therefore, we hypothesized that this interaction may affect the cell's capacity to correct lesions in the genome. When tested in two independent assays that measure NER (unscheduled DNA synthesis and host cell reactivation), the expression of HBx significantly inhibited the ability of cells to repair damaged DNA. Under the assay conditions, HBx was expressed at a level similar to that previously observed during natural viral infection and was able to transactivate several target reporter genes. These results are consistent with a model in which HBx acts as a cofactor in hepatocarcinogenesis by preventing the cell from efficiently repairing damaged DNA, thus leading to an accumulation of DNA mutations and, eventually, cancer. An adverse effect on cellular DNA repair processes suggests a new mechanism by which a tumor- associated virus might contribute to carcinogenesis.


This article has been cited by other articles:

  • Sung, W.-K., Lu, Y., Lee, C. W. H., Zhang, D., Ronaghi, M., Lee, C. G. L. (2009). Deregulated Direct Targets of the Hepatitis B Virus (HBV) Protein, HBx, Identified through Chromatin Immunoprecipitation and Expression Microarray Profiling. J. Biol. Chem. 284: 21941-21954 [Abstract] [Full Text]  
  • Hodgson, A. J., Keasler, V. V., Slagle, B. L. (2008). Premature Cell Cycle Entry Induced by Hepatitis B Virus Regulatory HBx Protein during Compensatory Liver Regeneration. Cancer Res. 68: 10341-10348 [Abstract] [Full Text]  
  • Hsieh, Y.-H., Su, I.-J., Wang, H.-C., Tsai, J.-H., Huang, Y.-J., Chang, W.-W., Lai, M.-D., Lei, H.-Y., Huang, W. (2007). Hepatitis B Virus Pre-S2 Mutant Surface Antigen Induces Degradation of Cyclin-Dependent Kinase Inhibitor p27Kip1 through c-Jun Activation Domain-Binding Protein 1. Mol Cancer Res 5: 1063-1072 [Abstract] [Full Text]  
  • Keasler, V. V., Hodgson, A. J., Madden, C. R., Slagle, B. L. (2007). Enhancement of Hepatitis B Virus Replication by the Regulatory X Protein In Vitro and In Vivo. J. Virol. 81: 2656-2662 [Abstract] [Full Text]  
  • Schrofelbauer, B., Hakata, Y., Landau, N. R. (2007). HIV-1 Vpr function is mediated by interaction with the damage-specific DNA-binding protein DDB1. Proc. Natl. Acad. Sci. USA 104: 4130-4135 [Abstract] [Full Text]  
  • Lee, A. T. C., Ren, J., Wong, E.-T., Ban, K. H. K., Lee, L. A., Lee, C. G. L. (2005). The Hepatitis B Virus X Protein Sensitizes HepG2 Cells to UV Light-induced DNA Damage. J. Biol. Chem. 280: 33525-33535 [Abstract] [Full Text]  
  • Bouchard, M. J., Schneider, R. J. (2004). The Enigmatic X Gene of Hepatitis B Virus. J. Virol. 78: 12725-12734 [Full Text]  
  • Shih, W.-L., Kuo, M.-L., Chuang, S.-E., Cheng, A.-L., Doong, S.-L. (2003). Hepatitis B Virus X Protein Activates a Survival Signaling by Linking Src to Phosphatidylinositol 3-Kinase. J. Biol. Chem. 278: 31807-31813 [Abstract] [Full Text]  
  • Chung, T.-W., Lee, Y.-C., Ko, J.-H., Kim, C.-H. (2003). Hepatitis B Virus X Protein Modulates the Expression of PTEN by Inhibiting the Function of p53, a Transcriptional Activator in Liver Cells. Cancer Res. 63: 3453-3458 [Abstract] [Full Text]  
  • Leupin, O., Bontron, S., Strubin, M. (2003). Hepatitis B Virus X Protein and Simian Virus 5 V Protein Exhibit Similar UV-DDB1 Binding Properties To Mediate Distinct Activities. J. Virol. 77: 6274-6283 [Abstract] [Full Text]  
  • Madden, C. R., Finegold, M. J., Slagle, B. L. (2002). Altered DNA Mutation Spectrum in Aflatoxin B1-Treated Transgenic Mice That Express the Hepatitis B Virus X Protein. J. Virol. 76: 11770-11774 [Abstract] [Full Text]  
  • Bontron, S., Lin-Marq, N., Strubin, M. (2002). Hepatitis B Virus X Protein Associated with UV-DDB1 Induces Cell Death in the Nucleus and Is Functionally Antagonized by UV-DDB2. J. Biol. Chem. 277: 38847-38854 [Abstract] [Full Text]  
  • Xu, Z., Yen, T. S. B., Wu, L., Madden, C. R., Tan, W., Slagle, B. L., Ou, J.-h. (2002). Enhancement of Hepatitis B Virus Replication by Its X Protein in Transgenic Mice. J. Virol. 76: 2579-2584 [Abstract] [Full Text]  
  • Waris, G., Huh, K.-W., Siddiqui, A. (2001). Mitochondrially Associated Hepatitis B Virus X Protein Constitutively Activates Transcription Factors STAT-3 and NF-kappa B via Oxidative Stress. Mol. Cell. Biol. 21: 7721-7730 [Abstract] [Full Text]  
  • Nag, A., Datta, A., Yoo, K., Bhattacharyya, D., Chakrabortty, A., Wang, X., Slagle, B. L., Costa, R. H., Raychaudhuri, P. (2001). DDB2 Induces Nuclear Accumulation of the Hepatitis B Virus X Protein Independently of Binding to DDB1. J. Virol. 75: 10383-10392 [Abstract] [Full Text]  
  • Madden, C. R., Finegold, M. J., Slagle, B. L. (2001). Hepatitis B Virus X Protein Acts as a Tumor Promoter in Development of Diethylnitrosamine-Induced Preneoplastic Lesions. J. Virol. 75: 3851-3858 [Abstract] [Full Text]  
  • Henkler, F., Hoare, J., Waseem, N., Goldin, R. D., McGarvey, M. J., Koshy, R., King, I. A. (2001). Intracellular localization of the hepatitis B virus HBx protein. J. Gen. Virol. 82: 871-882 [Abstract] [Full Text]  
  • Smela, M. E., Currier, S. S., Bailey, E. A., Essigmann, J. M. (2001). The chemistry and biology of aflatoxin B1: from mutational spectrometry to carcinogenesis. Carcinogenesis 22: 535-545 [Abstract] [Full Text]  
  • Madden, C. R., Finegold, M. J., Slagle, B. L. (2000). Expression of Hepatitis B Virus X Protein Does Not Alter the Accumulation of Spontaneous Mutations in Transgenic Mice. J. Virol. 74: 5266-5272 [Abstract] [Full Text]  
  • Butel, J. S. (2000). Viral carcinogenesis: revelation of molecular mechanisms and etiology of human disease. Carcinogenesis 21: 405-426 [Abstract] [Full Text]  
  • WOOD, R.D., ARAUJO, S.J., ARIZA, R.R., BATTY, D.P., BIGGERSTAFF, M., EVANS, E., GAILLARD, P.-H., GUNZ, D., KOBERLE, B., KURAOKA, I., MOGGS, J.G., SANDALL, J.K., SHIVJI, M.K.K. (2000). DNA Damage Recognition and Nucleotide Excision Repair in Mammalian Cells. Cold Spring Harb Symp Quant Biol 65: 173-182 [Abstract]  
  • Shiyanov, P., Hayes, S. A., Donepudi, M., Nichols, A. F., Linn, S., Slagle, B. L., Raychaudhuri, P. (1999). The Naturally Occurring Mutants of DDB Are Impaired in Stimulating Nuclear Import of the p125 Subunit and E2F1-Activated Transcription. Mol. Cell. Biol. 19: 4935-4943 [Abstract] [Full Text]  
  • Kao, S.-Y., Marriott, S. J. (1999). Disruption of Nucleotide Excision Repair by the Human T-Cell Leukemia Virus Type 1 Tax Protein. J. Virol. 73: 4299-4304 [Abstract] [Full Text]  
  • Groisman, I. J., Koshy, R., Henkler, F., Groopman, J. D., Alaoui-Jamali, M. A. (1999). Downregulation of DNA excision repair by the hepatitis B virus-x protein occurs in p53-proficient and p53-deficient cells. Carcinogenesis 20: 479-483 [Abstract] [Full Text]  
  • Choi, B. H., Park, G. T., Rho, H. M. (1999). Interaction of Hepatitis B Viral X Protein and CCAAT/ Enhancer-binding Protein alpha  Synergistically Activates the Hepatitis B Viral Enhancer II/Pregenomic Promoter. J. Biol. Chem. 274: 2858-2865 [Abstract] [Full Text]  
  • Prost, S., Ford, J. M., Taylor, C., Doig, J., Harrison, D. J. (1998). Hepatitis B x Protein Inhibits p53-dependent DNA Repair in Primary Mouse Hepatocytes. J. Biol. Chem. 273: 33327-33332 [Abstract] [Full Text]  
  • Nichols, A. F., Itoh, T., Graham, J. A., Liu, W., Yamaizumi, M., Linn, S. (2000). Human Damage-specific DNA-binding Protein p48. CHARACTERIZATION OF XPE MUTATIONS AND REGULATION FOLLOWING UV IRRADIATION. J. Biol. Chem. 275: 21422-21428 [Abstract] [Full Text]  
  • Shih, W.-L., Kuo, M.-L., Chuang, S.-E., Cheng, A.-L., Doong, S.-L. (2000). Hepatitis B Virus X Protein Inhibits Transforming Growth Factor-beta -induced Apoptosis through the Activation of Phosphatidylinositol 3-Kinase Pathway. J. Biol. Chem. 275: 25858-25864 [Abstract] [Full Text]  
  • Jaitovitch-Groisman, I., Fotouhi-Ardakani, N., Schecter, R. L., Woo, A., Alaoui-Jamali, M. A., Batist, G. (2000). Modulation of Glutathione S-Transferase Alpha by Hepatitis B Virus and the Chemopreventive Drug Oltipraz. J. Biol. Chem. 275: 33395-33403 [Abstract] [Full Text]  
  • Kao, S.-Y., Lemoine, F. J., Marriott, S. J. (2000). Suppression of DNA Repair by Human T Cell Leukemia Virus Type 1 Tax Is Rescued by a Functional p53 Signaling Pathway. J. Biol. Chem. 275: 35926-35931 [Abstract] [Full Text]  
  • Diao, J., Khine, A. A., Sarangi, F., Hsu, E., Iorio, C., Tibbles, L. A., Woodgett, J. R., Penninger, J., Richardson, C. D. (2001). X Protein of Hepatitis B Virus Inhibits Fas-mediated Apoptosis and Is Associated with Up-regulation of the SAPK/JNK Pathway. J. Biol. Chem. 276: 8328-8340 [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»