Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Short Report
  • Published:

Transcriptional repression of the human p53 gene by hepatitis B viral X protein

Oncogene volume 19, pages 468–471 (2000)Cite this article

Abstract

Hepatitis B viral X protein (HBx) and the human p53 protein (p53) have been known as a transactivator and as a tumor suppressor, respectively. These two proteins have also been known to interact with each other to neutralize their authentic functions and the p53 represses the HBV enhancer/X promoter activity. Here we report that the promoter activity of the human p53 gene was strongly repressed by the HBx using the chloramphenicol acetyl transferase (CAT) assay. Analyses of serial deletion, site-directed mutagenesis and the heterologous promoter system showed that the site responsible for the repression was the E-box element in the promoter of the p53 gene. In addition, HBx as expected also repressed the activation of the p53 promoter by c-Myc through the E-box element. Northern blot analyses also showed that the expression of the p53 gene in the HepG2-K8 cell line, which expresses HBV genes including HBx, was much more repressed than that of the control cell HepG2. These results with previous data suggest that the shift of the reciprocal inhibitory activities at the levels of protein-protein interaction and transcription between HBx and p53 may play a decisive role in the HBV-related hepatocarcinogenesis.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  • Aguilar F, Harris CC, Sun T, Hollstein M and Cerutti P. . 1994 Science 264: 1317–1319.

  • Becker SA, Lee TH, Butel JS and Slagle BL. . 1998 J. Virol. 72: 266–272.

  • Bienz-Tadmor B, Zakut-Houri R, Libresco S, Givol D and Oren M. . 1985 EMBO J. 4: 3209–3213.

  • Caselmann WH. . 1996 Adv. Virus Res. 47: 303–351.

  • Choi BH, Park GT and Rho HM. . 1999 J. Biol. Chem. 274: 2858–2865.

  • Choi CY, Choi BH, Park GT and Rho HM. . 1997 J. Biol. Chem. 272: 16934–16939.

  • Chomczynski P and Sacchi N. . 1987 Anal. Biochem. 162: 156–159.

  • Feitelson MA, Zhu M, Duan LX and London WT. . 1993 Oncogene 8: 1109–1117.

  • Furlong EE, Rein T and Martin F. . 1996 Mol. Cell. Biol. 16: 5933–5945.

  • Ganem D and Varmus HE. . 1987 Ann. Rev. Biochem. 56: 651–695.

  • Hsu IC, Metcalf RA, Sun T, Welsh JA, Wang NJ and Harris CC. . 1991 Nature 350: 427–428.

  • Kim CM, Koike K, Saito I, Miyamura T and Gilbert J. . 1991 Nature 351: 317–320.

  • Kim SH, Hong SP, Kim SK, Lee WS and Rho HM. . 1992 J. Gen. Virol. 73: 2421–2424.

  • Klein NP and Schneider RJ. . 1997 Mol. Cell. Biol. 17: 6427–6436.

  • Lane D. . 1992 Nature 358: 15–16.

  • Levine AJ. . 1993 Ann. Rev. Biochem. 62: 623–651.

  • Li CJ, Wang C, Friedman DJ and Pardee AB. . 1995 Proc. Natl. Acad. Sci. USA 92: 5461–5464.

  • Murre C, McCaw PS, Vaessin H, Caudy M, Jan LY, Jan YN, Cabrera CV, Buskin JN, Hauschka SD and Lassar AB. . 1989 Cell 58: 537–544.

  • Mutoh H, Fung BP, Naya FJ, Tsai MJ, Nishitani J and Leiter AB. . 1997 Proc. Natl. Acad. Sci. USA 94: 3560–3564.

  • Naya FJ, Stellrecht CM and Tsai MJ. . 1995 Genes Dev. 9: 1009–1019.

  • Ori A, Zauberman A, Doitsh G, Paran N, Oren M and Shaul Y. . 1998 EMBO J. 17: 544–553.

  • Ray RB, Steele R, Meyer K and Ray R. . 1997 J. Biol. Chem. 272: 10983–10986.

  • Reisman D and Rotter V. . 1993 Nucleic Acids Res. 21: 345–350.

  • Roy B, Beamon J, Balint E and Reisman D. . 1994 Mol. Cell. Biol. 14: 7805–7815.

  • Summers J and Mason WS. . 1982 Cell 29: 403–415.

  • Sun X, Shimizu H and Yamamoto K. . 1995 Mol. Cell. Biol. 15: 4489–4496.

  • Teodoro JG and Branton PE. . 1997 J. Virol. 71: 1739–1746.

  • Uittenbogaard MN, Giebler HA, Reisman D and Nyborg JK. . 1995 J. Biol. Chem. 270: 28503–28506.

  • Wang HD, Trivedi A and Johnson DL. . 1997 Mol. Cell. Biol. 17: 6838–6846.

  • Wang XW, Forrester K, Yeh H, Feitelson MA, Gu JR and Harris CC. . 1994 Proc. Natl. Acad. Sci. USA 91: 2230–2234.

  • Weintraub H. . 1993 Cell 75: 1241–1244.

  • Yen TSB. . 1996 J. Biomed. Sci. 3: 20–30.

Download references

Acknowledgements

We thank Professor David Reisman of University of South Carolina for the kind gift of p53plCAT, p53 promoter-CAT reporter plasmid. This work was supported in part by research grants from the Korean Ministry of Education, from Molecular Medicine Research Program (98-J03-01-01-A-04) of the Ministry of Science and Technology (MOST) and from Korea Science and Engineering Foundation (KOSEF) through the Research Center for Cell Differentiation.

Author information

Authors and Affiliations

  1. Department of Molecular Biology and Research Center for Cell Differentiation, Seoul National University, Seoul, 151-742, Korea

    Seok Geun Lee & Hyune Mo Rho

Authors
  1. Seok Geun Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hyune Mo Rho
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lee, S., Rho, H. Transcriptional repression of the human p53 gene by hepatitis B viral X protein. Oncogene 19, 468–471 (2000). https://doi.org/10.1038/sj.onc.1203312

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1203312

Keywords

This article is cited by

Search

Advanced search

Quick links