Skip to main content
NCBI home page
Journal of Virology logoLink to Journal of Virology
. 1991 May;65(5):2351–2356. doi: 10.1128/jvi.65.5.2351-2356.1991

Mutual functional antagonism of the simian virus 40 T antigen and the hepatitis B virus trans activator.

E Seto 1, T S Yen 1
PMCID: PMC240586  PMID: 1850016

Abstract

The hepatitis B virus X protein (pX) trans activates transcription of a wide variety of viral and cellular genes, apparently by interacting with multiple cellular transcription factors. It has been shown previously that the simian virus 40 early-region gene products (large-T and small-t antigens) prevent trans activation by pX. We show here that this phenomenon can be ascribed solely to the large-T antigen and that T antigen binds to pX in vitro. Mapping studies reveal that the region of large-T antigen around residues 125 and 126 is critical for this binding and also for the ability of T antigen to prevent trans activation by pX. Furthermore, pX in turn interferes with two of the known functions of T antigen, transcriptional trans activation and simian virus 40 DNA replication. We propose that pX and T antigen inactivate each other by forming a nonfunctional complex in vivo.

Full text

PDF
2351

Images in this article

2353Image
on p.2353
2353Image
on p.2353
2355Image
on p.2355

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Asselin C., Bastin M. Sequences from polyomavirus and simian virus 40 large T genes capable of immortalizing primary rat embryo fibroblasts. J Virol. 1985 Dec;56(3):958–968. doi: 10.1128/jvi.56.3.958-968.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Brady J., Bolen J. B., Radonovich M., Salzman N., Khoury G. Stimulation of simian virus 40 late gene expression by simian virus 40 tumor antigen. Proc Natl Acad Sci U S A. 1984 Apr;81(7):2040–2044. doi: 10.1073/pnas.81.7.2040. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Butel J. S. SV40 large T-antigen: dual oncogene. Cancer Surv. 1986;5(2):343–365. [PubMed] [Google Scholar]
  4. Chang L. S., Pater M. M., Hutchinson N. I., di Mayorca G. Transformation by purified early genes of simian virus 40. Virology. 1984 Mar;133(2):341–353. doi: 10.1016/0042-6822(84)90400-8. [DOI] [PubMed] [Google Scholar]
  5. Colgrove R., Simon G., Ganem D. Transcriptional activation of homologous and heterologous genes by the hepatitis B virus X gene product in cells permissive for viral replication. J Virol. 1989 Sep;63(9):4019–4026. doi: 10.1128/jvi.63.9.4019-4026.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. DeCaprio J. A., Ludlow J. W., Figge J., Shew J. Y., Huang C. M., Lee W. H., Marsilio E., Paucha E., Livingston D. M. SV40 large tumor antigen forms a specific complex with the product of the retinoblastoma susceptibility gene. Cell. 1988 Jul 15;54(2):275–283. doi: 10.1016/0092-8674(88)90559-4. [DOI] [PubMed] [Google Scholar]
  7. Dyson N., Buchkovich K., Whyte P., Harlow E. The cellular 107K protein that binds to adenovirus E1A also associates with the large T antigens of SV40 and JC virus. Cell. 1989 Jul 28;58(2):249–255. doi: 10.1016/0092-8674(89)90839-8. [DOI] [PubMed] [Google Scholar]
  8. Ewen M. E., Ludlow J. W., Marsilio E., DeCaprio J. A., Millikan R. C., Cheng S. H., Paucha E., Livingston D. M. An N-terminal transformation-governing sequence of SV40 large T antigen contributes to the binding of both p110Rb and a second cellular protein, p120. Cell. 1989 Jul 28;58(2):257–267. doi: 10.1016/0092-8674(89)90840-4. [DOI] [PubMed] [Google Scholar]
  9. Gluzman Y. SV40-transformed simian cells support the replication of early SV40 mutants. Cell. 1981 Jan;23(1):175–182. doi: 10.1016/0092-8674(81)90282-8. [DOI] [PubMed] [Google Scholar]
  10. Jackson S. P., MacDonald J. J., Lees-Miller S., Tjian R. GC box binding induces phosphorylation of Sp1 by a DNA-dependent protein kinase. Cell. 1990 Oct 5;63(1):155–165. doi: 10.1016/0092-8674(90)90296-q. [DOI] [PubMed] [Google Scholar]
  11. Kalderon D., Oostra B. A., Ely B. K., Smith A. E. Deletion loop mutagenesis: a novel method for the construction of point mutations using deletion mutants. Nucleic Acids Res. 1982 Sep 11;10(17):5161–5171. doi: 10.1093/nar/10.17.5161. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kalderon D., Richardson W. D., Markham A. F., Smith A. E. Sequence requirements for nuclear location of simian virus 40 large-T antigen. Nature. 1984 Sep 6;311(5981):33–38. doi: 10.1038/311033a0. [DOI] [PubMed] [Google Scholar]
  13. Kalderon D., Smith A. E. In vitro mutagenesis of a putative DNA binding domain of SV40 large-T. Virology. 1984 Nov;139(1):109–137. doi: 10.1016/0042-6822(84)90334-9. [DOI] [PubMed] [Google Scholar]
  14. Keller J. M., Alwine J. C. Analysis of an activatable promoter: sequences in the simian virus 40 late promoter required for T-antigen-mediated trans activation. Mol Cell Biol. 1985 Aug;5(8):1859–1869. doi: 10.1128/mcb.5.8.1859. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kelly T. J. SV40 DNA replication. J Biol Chem. 1988 Dec 5;263(34):17889–17892. [PubMed] [Google Scholar]
  16. Koike K., Shirakata Y., Yaginuma K., Arii M., Takada S., Nakamura I., Hayashi Y., Kawada M., Kobayashi M. Oncogenic potential of hepatitis B virus. Mol Biol Med. 1989 Apr;6(2):151–160. [PubMed] [Google Scholar]
  17. Lane D. P., Crawford L. V. T antigen is bound to a host protein in SV40-transformed cells. Nature. 1979 Mar 15;278(5701):261–263. doi: 10.1038/278261a0. [DOI] [PubMed] [Google Scholar]
  18. Lanford R. E., Butel J. S. Construction and characterization of an SV40 mutant defective in nuclear transport of T antigen. Cell. 1984 Jul;37(3):801–813. doi: 10.1016/0092-8674(84)90415-x. [DOI] [PubMed] [Google Scholar]
  19. Levine A. J. The p53 protein and its interactions with the oncogene products of the small DNA tumor viruses. Virology. 1990 Aug;177(2):419–426. doi: 10.1016/0042-6822(90)90505-l. [DOI] [PubMed] [Google Scholar]
  20. Li J. J., Kelly T. J. Simian virus 40 DNA replication in vitro: specificity of initiation and evidence for bidirectional replication. Mol Cell Biol. 1985 Jun;5(6):1238–1246. doi: 10.1128/mcb.5.6.1238. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Linzer D. I., Levine A. J. Characterization of a 54K dalton cellular SV40 tumor antigen present in SV40-transformed cells and uninfected embryonal carcinoma cells. Cell. 1979 May;17(1):43–52. doi: 10.1016/0092-8674(79)90293-9. [DOI] [PubMed] [Google Scholar]
  22. Livingston D. M., Bradley M. K. The simian virus 40 large T antigen. A lot packed into a little. Mol Biol Med. 1987 Apr;4(2):63–80. [PubMed] [Google Scholar]
  23. Loeken M., Bikel I., Livingston D. M., Brady J. trans-activation of RNA polymerase II and III promoters by SV40 small t antigen. Cell. 1988 Dec 23;55(6):1171–1177. doi: 10.1016/0092-8674(88)90261-9. [DOI] [PubMed] [Google Scholar]
  24. McCormick F., Clark R., Harlow E., Tjian R. SV40 T antigen binds specifically to a cellular 53 K protein in vitro. Nature. 1981 Jul 2;292(5818):63–65. doi: 10.1038/292063a0. [DOI] [PubMed] [Google Scholar]
  25. Mitchell P. J., Wang C., Tjian R. Positive and negative regulation of transcription in vitro: enhancer-binding protein AP-2 is inhibited by SV40 T antigen. Cell. 1987 Sep 11;50(6):847–861. doi: 10.1016/0092-8674(87)90512-5. [DOI] [PubMed] [Google Scholar]
  26. Mohr I. J., Gluzman Y., Fairman M. P., Strauss M., McVey D., Stillman B., Gerard R. D. Production of simian virus 40 large tumor antigen in bacteria: altered DNA-binding specificity and dna-replication activity of underphosphorylated large tumor antigen. Proc Natl Acad Sci U S A. 1989 Sep;86(17):6479–6483. doi: 10.1073/pnas.86.17.6479. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Peden K. W., Pipas J. M. Site-directed mutagenesis of the simian virus 40 large T-antigen gene: replication-defective amino acid substitution mutants that retain the ability to induce morphological transformation. J Virol. 1985 Jul;55(1):1–9. doi: 10.1128/jvi.55.1.1-9.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Pipas J. M., Adler S. P., Peden K. W., Nathans D. Deletion mutants of SV40 that affect the structure of viral tumor antigens. Cold Spring Harb Symp Quant Biol. 1980;44(Pt 1):285–291. doi: 10.1101/sqb.1980.044.01.032. [DOI] [PubMed] [Google Scholar]
  29. Pipas J. M., Peden K. W., Nathans D. Mutational analysis of simian virus 40 T antigen: isolation and characterization of mutants with deletions in the T-antigen gene. Mol Cell Biol. 1983 Feb;3(2):203–213. doi: 10.1128/mcb.3.2.203. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Razzaque A., Mizusawa H., Seidman M. M. Rearrangement and mutagenesis of a shuttle vector plasmid after passage in mammalian cells. Proc Natl Acad Sci U S A. 1983 May;80(10):3010–3014. doi: 10.1073/pnas.80.10.3010. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Sawai E. T., Butel J. S. Association of a cellular heat shock protein with simian virus 40 large T antigen in transformed cells. J Virol. 1989 Sep;63(9):3961–3973. doi: 10.1128/jvi.63.9.3961-3973.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Schmieg F. I., Simmons D. T. Characterization of the in vitro interaction between SV40 T antigen and p53: mapping the p53 binding site. Virology. 1988 May;164(1):132–140. doi: 10.1016/0042-6822(88)90628-9. [DOI] [PubMed] [Google Scholar]
  33. Seto E., Mitchell P. J., Yen T. S. Transactivation by the hepatitis B virus X protein depends on AP-2 and other transcription factors. Nature. 1990 Mar 1;344(6261):72–74. doi: 10.1038/344072a0. [DOI] [PubMed] [Google Scholar]
  34. Seto E., Yen T. S., Peterlin B. M., Ou J. H. Trans-activation of the human immunodeficiency virus long terminal repeat by the hepatitis B virus X protein. Proc Natl Acad Sci U S A. 1988 Nov;85(21):8286–8290. doi: 10.1073/pnas.85.21.8286. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Seto E., Zhou D. X., Peterlin B. M., Yen T. S. trans-activation by the hepatitis B virus X protein shows cell-type specificity. Virology. 1989 Dec;173(2):764–766. doi: 10.1016/0042-6822(89)90594-1. [DOI] [PubMed] [Google Scholar]
  36. Siddiqui A., Gaynor R., Srinivasan A., Mapoles J., Farr R. W. trans-activation of viral enhancers including long terminal repeat of the human immunodeficiency virus by the hepatitis B virus X protein. Virology. 1989 Apr;169(2):479–484. doi: 10.1016/0042-6822(89)90177-3. [DOI] [PubMed] [Google Scholar]
  37. Smale S. T., Tjian R. T-antigen-DNA polymerase alpha complex implicated in simian virus 40 DNA replication. Mol Cell Biol. 1986 Nov;6(11):4077–4087. doi: 10.1128/mcb.6.11.4077. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Spandau D. F., Lee C. H. trans-activation of viral enhancers by the hepatitis B virus X protein. J Virol. 1988 Feb;62(2):427–434. doi: 10.1128/jvi.62.2.427-434.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Twu J. S., Rosen C. A., Haseltine W. A., Robinson W. S. Identification of a region within the human immunodeficiency virus type 1 long terminal repeat that is essential for transactivation by the hepatitis B virus gene X. J Virol. 1989 Jun;63(6):2857–2860. doi: 10.1128/jvi.63.6.2857-2860.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Wang E. H., Friedman P. N., Prives C. The murine p53 protein blocks replication of SV40 DNA in vitro by inhibiting the initiation functions of SV40 large T antigen. Cell. 1989 May 5;57(3):379–392. doi: 10.1016/0092-8674(89)90913-6. [DOI] [PubMed] [Google Scholar]
  41. Zhou D. X., Taraboulos A., Ou J. H., Yen T. S. Activation of class I major histocompatibility complex gene expression by hepatitis B virus. J Virol. 1990 Aug;64(8):4025–4028. doi: 10.1128/jvi.64.8.4025-4028.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES