1887

Abstract

Bovine papillomavirus 4 (BPV-4) is a mucosal epitheliotropic papillomavirus. It encodes a transcriptional regulator, E2, which acts on the BPV-4 transcriptional control region (the long control region or LCR) to regulate transcription. The distribution of E2 binding sites within the LCR of BPV- 4 is identical to that of the human papillomaviruses HPV-16 and HPV-18, indicating that the mechanism of transcriptional control by E2 of mucosal epitheliotropic papillomaviruses is conserved. In this study it has been shown that E2 activates transcription through the BPV-4 LCR promoter in primary bovine palate keratinocytes but not in primary bovine palate fibroblasts. The epithelial specific transcriptional activation of the BPV-4 LCR by E2 is promoter-specific because following binding to the BPV-4 LCR placed in an enhancer mode, E2 can activate transcription from heterologous promoters, such as SV40, in both keratinocytes and fibroblasts. Chimaeric VP16-E2 molecules suggest that the epithelial specific transcriptional activation of the BPV-4 LCR promoter is mediated by the E2 transactivation domain. Although low to intermediate levels of E2 can activate transcription from the BPV-4 LCR promoter, high levels of E2 result in down-regulation of transcription from this promoter in keratinocytes. Mutation of E2 binding site 1 (BS1), which is 3 bp upstream from the TATA box, abrogates down-regulation of transcription by high levels of E2. The results present a model system for studying transcriptional regulation of mucosal epi- theliotropic papillomavirus LCRs by E2.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-79-3-501
1998-03-01
2022-01-21
Loading full text...

Full text loading...

/deliver/fulltext/jgv/79/3/9519828.html?itemId=/content/journal/jgv/10.1099/0022-1317-79-3-501&mimeType=html&fmt=ahah

References

  1. Baker C. C., Phelps W. C., Lingdren V., Bram M. J., Gonda M. A., Howley P. M. 1987; Structural and transcriptional analysis of human papillomavirus type 16 sequences in cervical carcinoma cell lines. Journal of Virology 61:962–971
    [Google Scholar]
  2. Bouvard V., Storey A., Pim D., Banks L. 1994; Characterization of the human papillomavirus E2 protein: evidence of trans-activation and trans-repression in cervical keratinocytes. EMBO Journal 13:5451–5459
    [Google Scholar]
  3. Campo M. S., O’Neil B. W., Barron R. J., Jarrett W. F. H. 1994; Experimental reproduction of the papilloma-carcinoma complex of the alimentary canal in cattle. Carcinogenesis 15:1597–1601
    [Google Scholar]
  4. Cripe T. P., Haugen T. H., Turk J. P., Tabatabai F., Schmid P. G., Durst M., Gissmann L., Roman A., Turek L. P. 1987; Transcriptional regulation of the human papillomavirus-16 E6-E7 promoter by a keratinocyte-dependent enhancer, and by viral E2 trans-activator and repressor gene products - implications for cervical carcinogenesis. EMBO Journal 6:3745–3753
    [Google Scholar]
  5. Cuthill S., Sibbet G. J., Campo M. S. 1993; Characterisation of a nuclear factor, papillomavirus enhancer binding factor 1, that binds to the long control region of human papillomavirus type 16 and contributes to enhancer activity. Molecular Carcinogenesis 8:96–104
    [Google Scholar]
  6. Demeret C., Yaniv M., Thierry F. 1994; The E2 transcriptional repressor can compensate for SP1 activation of the human papillomavirus type 18 early promoter. Journal of Virology 68:7075–7082
    [Google Scholar]
  7. Demeret C., Le Moal M., Yaniv M., Thierry F. 1995; Control of HPV18 DNA replication by cellular and viral transcription factors. Nucleic Acids Research 23:4777–4784
    [Google Scholar]
  8. Dong G., Broker T. R., Chow L. T. 1994; Human papillomavirus type 11 E2 proteins repress the homologous E6 promoter by interfering with the binding of host transcription factors to adjacent elements. Journal of Virology 68:1115–1127
    [Google Scholar]
  9. Ferguson M. K., Botchan M. R. 1996; Genetic analysis of the activation domain of bovine papillomavirus protein E2 : its role in transcription and replication. Journal of Virology 70:4193–4199
    [Google Scholar]
  10. Giri I., Yaniv M. 1988a; Study of the E2 gene product of the cottontail rabbit papillomavirus reveals a common mechanism of transactivation among papillomaviruses. Journal of Virology 62:1573–1581
    [Google Scholar]
  11. Giri I., Yaniv M. 1988b; Structural and mutational analysis of E2 trans-activating proteins of papillomaviruses reveals three distinct functional domains. EMBO Journal 7:2823–2829
    [Google Scholar]
  12. Grossel M. J., Sverdrup F., Breiding D. E., Androphy E. J. 1996; Transcriptional activation function is not required for stimulation of DNA-replication by bovine papillomavirus type-1 E2. Journal of Virology 70:7264–7269
    [Google Scholar]
  13. Ham J., Dostatni N., Gauthier J. M., Yaniv M. 1991a; The papillomavirus E2 protein: a factor with many talents. Trends in Biochemical Sciences 16:440–444
    [Google Scholar]
  14. Ham J., Dostatni N., Arnos F., Yaniv M. 1991b; Several different upstream promoter elements can potentiate transactivation by the BPV- 1 E2 protein. EMBO Journal 10:2931–2940
    [Google Scholar]
  15. Ham J., Steger G., Yaniv M. 1994; Cooperativity in vivo between the E2 transactivator and the TATA box binding protein depends on core promoter structure. EMBO Journal 13:147–157
    [Google Scholar]
  16. Hoppe-Seyler F., Butz K. 1994; Cellular control of human papillomavirus oncogene transcription. Molecular Carcinogenesis 10:134–141
    [Google Scholar]
  17. Jackson M. E., Campo M. S. 1995; Both viral E2 protein and the cellular factor PEBP2 regulate transcription via E2 consensus sites within the bovine papillomavirus type 4 long control region. Journal of Virology 69:6038–6046
    [Google Scholar]
  18. Jaggar R. T., Pennie W. D., Smith K. T., Jackson M. E., Campo M. S. 1990; Co-operation between bovine papillomavirus type 4 and ras in the morphological transformation of primary bovine fibroblasts. Journal of General Virology 71:3041–3046
    [Google Scholar]
  19. Jiang C.-K., Connolly D., Blumenberg M. 1991; Comparison of methods for transfection of human epidermal keratinocytes. Journal of Investigative Dermatology 97:969–973
    [Google Scholar]
  20. Li R., Knight J. D., Jackson S. P., Tjian R., Botchan M. R. 1991; Direct interaction between Sp1 and the BPV enhancer E2 protein mediates synergistic activation of transcription. Cell 65:493–505
    [Google Scholar]
  21. Lu J. Z., Sun Y. N., Rose R. C., Bonnez W., McCance D. J. 1993; Two E2 binding sites (E2BS) alone or one E2BS plus an A/T-rich region are minimal requirements for the replication of the human papillomavirus type 11 origin. Journal of Virology 67:7131–7139
    [Google Scholar]
  22. McBride A. A., Schlegel R., Howley P. M. 1988; The carboxy- terminal domain shared by the bovine papillomavirus E2 transactivator and repressor proteins contain a specific DNA binding activity. EMBO Journal 7:533–539
    [Google Scholar]
  23. Monini P., Blitz I. L., Cassai E. 1993; Cooperative DNA binding of the bovine papillomavirus E2 transcriptional activator is antagonized by truncated E2 polypeptides. Journal of Virology 67:5668–5676
    [Google Scholar]
  24. Monini P., Grossman S. R., Pepinsky B., Androphy E. J., Laimins L. A. 1991; Cooperative binding of the E2 protein of bovine papillomavirus to adjacent E2-responsive sequences. Journal of Virology 65:2124–2130
    [Google Scholar]
  25. Morrissey L. C., Barsoum J., Androphy E. J. 1989; Transactivation by the bovine papillomavirus E2 protein in Saccharomyces cerevisiae . Journal of Virology 63:4422–4425
    [Google Scholar]
  26. Romanczuk H., Thierry F., Howley P. M. 1990; Mutational analysis of cis elements involved in E2 modulation of human papillomavirus type 16 P97 and type 18 P105 promoters. Journal of Virology 64:2849–2859
    [Google Scholar]
  27. Sakai H., Yasugi T., Benson J. D., Dowhanick J. J., Howley P. M. 1996; Targeted mutagenesis of the human papillomavirus type-16 E2 transactivation domain reveals separable transcriptional activation and DNA-replication functions. Journal of Virology 70:1602–1611
    [Google Scholar]
  28. Sandler A. B., Baker C. C., Spalholz B. A. 1996; Sp1 is critical for basal and E2-transactivated transcription from the bovine papillomavirus type 1 P89 promoter. Journal of General Virology 77:189–198
    [Google Scholar]
  29. Sang B. C., Barbosa M. S. 1992; Increased E6/E7 transcription in HPV18-immortalized human keratinocytes results from inactivation of E2 and additional cellular events. Journal of Virology 189:448–455
    [Google Scholar]
  30. Schwarz E., Freeze U. K., Gissman L., Mayer W., Roggenback B., Stremlau A., zur Hausen H. 1985; Structure and transcription of human papillomavirus sequences in cervical carcinoma cells. Nature 314:111–114
    [Google Scholar]
  31. Sedman J., Stenlund A. 1995; Co-operative interaction between the initiator E1 and the transcriptional activator E2 is required for replicator specific DNA replication of bovine papillomavirus in vivo and in vitro . EMBO Journal 14:6218–6228
    [Google Scholar]
  32. Seo Y. S., Muller F., Lusky M., Gibbs E., Kim H. Y., Phillips B., Hurwitz J. 1993; Bovine papilloma virus (BPV)-encoded E2 protein enhances binding of E1 protein to the BPV replication origin. Proceedings of the National Academy of Sciences, USA 90:2865–2869
    [Google Scholar]
  33. Stanway C. A., Sowden M. P., Wilson L. E., Kingsman A. J., Kingsman S. M. 1989; Efficient activation of transcription in yeast by the BPV1 E2 protein. Nucleic Acids Research 17:2187–2196
    [Google Scholar]
  34. Steger G., Corbach S. 1997; Dose-dependent regulation of the early promoter of human papillomavirus type-18 by the viral E2 protein. Journal of Virology 71:50–58
    [Google Scholar]
  35. Steger G., Ham J., Lefebvre O., Yaniv M. 1995; The bovine papillomavirus 1 E2 protein contains two activation domains: one that interacts with TBP and another that functions after TBP binding. EMBO Journal 14:329–340
    [Google Scholar]
  36. Stenlund A., Botchan M. R. 1990; The E2-trans-activator can act as a repressor by interfering with a cellular transcription factor. Genes & Development 4:123–136
    [Google Scholar]
  37. Storey A., Greenfield I., Banks L., Pim D., Crook T., Crawford L., Stanley M. 1992; Lack of immortalising activity of a human papillomavirus type 16 variant DNA with a mutation in the E2 gene isolated from normal human cervical keratinocytes. Oncogene 7:459–465
    [Google Scholar]
  38. Sverdrup F., Khan S. A. 1994; Replication of human papillomavirus (HPV) DNAs supported by the HPV type 18 E1 and E2 proteins. Journal of Virology 68:505–509
    [Google Scholar]
  39. Tan S. H., Gloss B., Bernard H. U. 1992; During negative regulation of the human papillomavirus-16 E6 promoter, the viral E2 protein can displace Sp1 from a proximal promoter element. Nucleic Acids Research 20:251–256
    [Google Scholar]
  40. Tan S. H., Leong L. E. C., Walker P. A., Bernard H. U. 1994; The human papillomavirus type 16 E2 transcription factor binds with low cooperativity to two flanking sites and represses the E6 promoter through displacement of Sp1 and TFIID. Journal of Virology 68:6411–6420
    [Google Scholar]
  41. Thierry F. 1996; HPV proteins in the control of HPV transcription. In Papillomavirus Reviews pp 21–29 Lacey C. Edited by Leeds: Leeds University Press;
    [Google Scholar]
  42. Thierry F., Yaniv M. 1987; The BPV1-E2 trans-acting protein can be either an activator or a repressor of the HPV18 regulatory region. EMBO Journal 6:3391–3397
    [Google Scholar]
  43. Ustav M., Stenlund A. 1991; Transient replication ofBPV-1 requires two viral polypeptides encoded by the E1 and E2 open reading frames. EMBO Journal 10:449–457
    [Google Scholar]
  44. Winokur P. L., McBride A. A. 1992; Separation ofthe transcriptional activation and replication functions of the bovine papillomavirus-1 E2 protein. EMBO Journal 11:4111–4118
    [Google Scholar]
  45. Yang L., Li R., Mohr I. J., Clark R., Botchan M. R. 1991; Activation of BPV-1 replication in vitro by the transcription factor E2. ature 353:628–632
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-79-3-501
Loading
/content/journal/jgv/10.1099/0022-1317-79-3-501
Loading

Data & Media loading...

Most cited this month Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error