Skip to main content
PMC home page
Journal of Virology logoLink to Journal of Virology
. 1996 Oct;70(10):7264–7269. doi: 10.1128/jvi.70.10.7264-7269.1996

Transcriptional activation function is not required for stimulation of DNA replication by bovine papillomavirus type 1 E2.

M J Grossel 1, F Sverdrup 1, D E Breiding 1, E J Androphy 1
PMCID: PMC190786  PMID: 8794380

Abstract

Bovine papillomavirus type 1 replication was previously shown to require both the E1 initiator protein and the E2 transactivator protein. We show here that E1, in the absence of E2, is sufficient for low-level bovine papillomavirus type 1 DNA replication in C-33A cells. In addition, studies of genetically isolated E2 point mutants demonstrate that enhancement of replication by E2 does not require its transcriptional activation function. The uncoupling of the E2 functions suggests that stimulation of transcription and replication by enhancer proteins occurs via divergent mechanisms.

Full Text

The Full Text of this article is available as a PDF (280.4 KB).

Selected References

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

  1. Baru M., Shlissel M., Manor H. The yeast GAL4 protein transactivates the polyomavirus origin of DNA replication in mouse cells. J Virol. 1991 Jul;65(7):3496–3503. doi: 10.1128/jvi.65.7.3496-3503.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bennett-Cook E. R., Hassell J. A. Activation of polyomavirus DNA replication by yeast GAL4 is dependent on its transcriptional activation domains. EMBO J. 1991 Apr;10(4):959–969. doi: 10.1002/j.1460-2075.1991.tb08030.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Berg L., Lusky M., Stenlund A., Botchan M. R. Repression of bovine papilloma virus replication is mediated by a virally encoded trans-acting factor. Cell. 1986 Aug 29;46(5):753–762. doi: 10.1016/0092-8674(86)90351-x. [DOI] [PubMed] [Google Scholar]
  4. Bonne-Andrea C., Santucci S., Clertant P. Bovine papillomavirus E1 protein can, by itself, efficiently drive multiple rounds of DNA synthesis in vitro. J Virol. 1995 May;69(5):3201–3205. doi: 10.1128/jvi.69.5.3201-3205.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Borowiec J. A., Dean F. B., Bullock P. A., Hurwitz J. Binding and unwinding--how T antigen engages the SV40 origin of DNA replication. Cell. 1990 Jan 26;60(2):181–184. doi: 10.1016/0092-8674(90)90730-3. [DOI] [PubMed] [Google Scholar]
  6. Breiding D. E., Grossel M. J., Androphy E. J. Genetic analysis of the bovine papillomavirus E2 transcriptional activation domain. Virology. 1996 Jul 1;221(1):34–43. doi: 10.1006/viro.1996.0350. [DOI] [PubMed] [Google Scholar]
  7. Brokaw J. L., Blanco M., McBride A. A. Amino acids critical for the functions of the bovine papillomavirus type 1 E2 transactivator. J Virol. 1996 Jan;70(1):23–29. doi: 10.1128/jvi.70.1.23-29.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Chen C., Okayama H. High-efficiency transformation of mammalian cells by plasmid DNA. Mol Cell Biol. 1987 Aug;7(8):2745–2752. doi: 10.1128/mcb.7.8.2745. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Clertant P., Seif I. A common function for polyoma virus large-T and papillomavirus E1 proteins? Nature. 1984 Sep 20;311(5983):276–279. doi: 10.1038/311276a0. [DOI] [PubMed] [Google Scholar]
  10. DePamphili M. L. How transcription factors regulate origins of DNA replication in eukaryotic cells. Trends Cell Biol. 1993 May;3(5):161–167. doi: 10.1016/0962-8924(93)90137-p. [DOI] [PubMed] [Google Scholar]
  11. Gilbert D. M., Cohen S. N. Bovine papilloma virus plasmids replicate randomly in mouse fibroblasts throughout S phase of the cell cycle. Cell. 1987 Jul 3;50(1):59–68. doi: 10.1016/0092-8674(87)90662-3. [DOI] [PubMed] [Google Scholar]
  12. Giri I., Yaniv M. Structural and mutational analysis of E2 trans-activating proteins of papillomaviruses reveals three distinct functional domains. EMBO J. 1988 Sep;7(9):2823–2829. doi: 10.1002/j.1460-2075.1988.tb03138.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gopalakrishnan V., Khan S. A. E1 protein of human papillomavirus type 1a is sufficient for initiation of viral DNA replication. Proc Natl Acad Sci U S A. 1994 Sep 27;91(20):9597–9601. doi: 10.1073/pnas.91.20.9597. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Guo Z. S., DePamphilis M. L. Specific transcription factors stimulate simian virus 40 and polyomavirus origins of DNA replication. Mol Cell Biol. 1992 Jun;12(6):2514–2524. doi: 10.1128/mcb.12.6.2514. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Heintz N. H. Transcription factors and the control of DNA replication. Curr Opin Cell Biol. 1992 Jun;4(3):459–467. doi: 10.1016/0955-0674(92)90012-2. [DOI] [PubMed] [Google Scholar]
  16. Hirt B. Selective extraction of polyoma DNA from infected mouse cell cultures. J Mol Biol. 1967 Jun 14;26(2):365–369. doi: 10.1016/0022-2836(67)90307-5. [DOI] [PubMed] [Google Scholar]
  17. Lambert P. F., Spalholz B. A., Howley P. M. A transcriptional repressor encoded by BPV-1 shares a common carboxy-terminal domain with the E2 transactivator. Cell. 1987 Jul 3;50(1):69–78. doi: 10.1016/0092-8674(87)90663-5. [DOI] [PubMed] [Google Scholar]
  18. Law M. F., Lowy D. R., Dvoretzky I., Howley P. M. Mouse cells transformed by bovine papillomavirus contain only extrachromosomal viral DNA sequences. Proc Natl Acad Sci U S A. 1981 May;78(5):2727–2731. doi: 10.1073/pnas.78.5.2727. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Li R., Botchan M. R. Acidic transcription factors alleviate nucleosome-mediated repression of DNA replication of bovine papillomavirus type 1. Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):7051–7055. doi: 10.1073/pnas.91.15.7051. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Li R., Botchan M. R. The acidic transcriptional activation domains of VP16 and p53 bind the cellular replication protein A and stimulate in vitro BPV-1 DNA replication. Cell. 1993 Jun 18;73(6):1207–1221. doi: 10.1016/0092-8674(93)90649-b. [DOI] [PubMed] [Google Scholar]
  21. Liu J. S., Kuo S. R., Broker T. R., Chow L. T. The functions of human papillomavirus type 11 E1, E2, and E2C proteins in cell-free DNA replication. J Biol Chem. 1995 Nov 10;270(45):27283–27291. doi: 10.1074/jbc.270.45.27283. [DOI] [PubMed] [Google Scholar]
  22. Lusky M., Hurwitz J., Seo Y. S. The bovine papillomavirus E2 protein modulates the assembly of but is not stably maintained in a replication-competent multimeric E1-replication origin complex. Proc Natl Acad Sci U S A. 1994 Sep 13;91(19):8895–8899. doi: 10.1073/pnas.91.19.8895. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. McBride A. A., Romanczuk H., Howley P. M. The papillomavirus E2 regulatory proteins. J Biol Chem. 1991 Oct 5;266(28):18411–18414. [PubMed] [Google Scholar]
  24. Mendoza R., Gandhi L., Botchan M. R. E1 recognition sequences in the bovine papillomavirus type 1 origin of DNA replication: interaction between half sites of the inverted repeats. J Virol. 1995 Jun;69(6):3789–3798. doi: 10.1128/jvi.69.6.3789-3798.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Mohr I. J., Clark R., Sun S., Androphy E. J., MacPherson P., Botchan M. R. Targeting the E1 replication protein to the papillomavirus origin of replication by complex formation with the E2 transactivator. Science. 1990 Dec 21;250(4988):1694–1699. doi: 10.1126/science.2176744. [DOI] [PubMed] [Google Scholar]
  26. Morrissey L. C., Barsoum J., Androphy E. J. Trans activation by the bovine papillomavirus E2 protein in Saccharomyces cerevisiae. J Virol. 1989 Oct;63(10):4422–4425. doi: 10.1128/jvi.63.10.4422-4425.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Nilsson M., Forsberg M., You Z. Y., Westin G., Magnusson G. Enhancer effect of bovine papillomavirus E2 protein in replication of polyomavirus DNA. Nucleic Acids Res. 1991 Dec;19(25):7061–7065. doi: 10.1093/nar/19.25.7061. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Peden K. W., Pipas J. M., Pearson-White S., Nathans D. Isolation of mutants of an animal virus in bacteria. Science. 1980 Sep 19;209(4463):1392–1396. doi: 10.1126/science.6251547. [DOI] [PubMed] [Google Scholar]
  29. Sakai H., Yasugi T., Benson J. D., Dowhanick J. J., Howley P. M. Targeted mutagenesis of the human papillomavirus type 16 E2 transactivation domain reveals separable transcriptional activation and DNA replication functions. J Virol. 1996 Mar;70(3):1602–1611. doi: 10.1128/jvi.70.3.1602-1611.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Seo Y. S., Müller F., Lusky M., Gibbs E., Kim H. Y., Phillips B., Hurwitz J. Bovine papilloma virus (BPV)-encoded E2 protein enhances binding of E1 protein to the BPV replication origin. Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):2865–2869. doi: 10.1073/pnas.90.7.2865. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Spalholz B. A., McBride A. A., Sarafi T., Quintero J. Binding of bovine papillomavirus E1 to the origin is not sufficient for DNA replication. Virology. 1993 Mar;193(1):201–212. doi: 10.1006/viro.1993.1116. [DOI] [PubMed] [Google Scholar]
  32. Sverdrup F., Khan S. A. Two E2 binding sites alone are sufficient to function as the minimal origin of replication of human papillomavirus type 18 DNA. J Virol. 1995 Feb;69(2):1319–1323. doi: 10.1128/jvi.69.2.1319-1323.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Tang W. J., Berger S. L., Triezenberg S. J., Folk W. R. Nucleotides in the polyomavirus enhancer that control viral transcription and DNA replication. Mol Cell Biol. 1987 May;7(5):1681–1690. doi: 10.1128/mcb.7.5.1681. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Ustav E., Ustav M., Szymanski P., Stenlund A. The bovine papillomavirus origin of replication requires a binding site for the E2 transcriptional activator. Proc Natl Acad Sci U S A. 1993 Feb 1;90(3):898–902. doi: 10.1073/pnas.90.3.898. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Ustav M., Stenlund A. Transient replication of BPV-1 requires two viral polypeptides encoded by the E1 and E2 open reading frames. EMBO J. 1991 Feb;10(2):449–457. doi: 10.1002/j.1460-2075.1991.tb07967.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Ustav M., Ustav E., Szymanski P., Stenlund A. Identification of the origin of replication of bovine papillomavirus and characterization of the viral origin recognition factor E1. EMBO J. 1991 Dec;10(13):4321–4329. doi: 10.1002/j.1460-2075.1991.tb05010.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Verrijzer C. P., Kal A. J., Van der Vliet P. C. The DNA binding domain (POU domain) of transcription factor oct-1 suffices for stimulation of DNA replication. EMBO J. 1990 Jun;9(6):1883–1888. doi: 10.1002/j.1460-2075.1990.tb08314.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Wilson T. E., Fahrner T. J., Johnston M., Milbrandt J. Identification of the DNA binding site for NGFI-B by genetic selection in yeast. Science. 1991 May 31;252(5010):1296–1300. doi: 10.1126/science.1925541. [DOI] [PubMed] [Google Scholar]
  39. Winokur P. L., McBride A. A. Separation of the transcriptional activation and replication functions of the bovine papillomavirus-1 E2 protein. EMBO J. 1992 Nov;11(11):4111–4118. doi: 10.1002/j.1460-2075.1992.tb05504.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Yang L., Li R., Mohr I. J., Clark R., Botchan M. R. Activation of BPV-1 replication in vitro by the transcription factor E2. Nature. 1991 Oct 17;353(6345):628–632. doi: 10.1038/353628a0. [DOI] [PubMed] [Google Scholar]

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

RESOURCES