1887

Abstract

The E7 protein encoded by human papillomavirus type 16 shows transforming and immortalizing activities which are mediated, in part, through the interaction of the viral oncoprotein with the pRB protein family. This interaction is not solely responsible for E7 function, however, and other properties of E7, such as the interaction with basal transcription factors such as TBP, are likely to be of importance. We show here that three regions of the viral protein contribute to the interaction between E7 and TBP; the pRB-binding domain, the casein kinase II phosphorylation region and the C-terminal dimerization domain. Mutations within each region reduced the interaction of E7 with TBP , and simultaneous alterations within each of these regions completely abrogated binding. Unlike the pRB interaction, the association of E7 with TBP was enhanced following phosphorylation of E7 by casein kinase II, demonstrating a functional significance for phosphorylation of the viral protein.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-78-4-905
1997-04-01
2024-12-08
Loading full text...

Full text loading...

/deliver/fulltext/jgv/78/4/9129664.html?itemId=/content/journal/jgv/10.1099/0022-1317-78-4-905&mimeType=html&fmt=ahah

References

  1. Arany Z., Sellers W. R., Livingston D. M., Eckner R. 1994; E1A-associated p300 and CREB-associated CBP belong to a conserved family of coactivators. Cell 77:799–800
    [Google Scholar]
  2. Banks L., Edmonds C., Vousden K. 1990; Ability of the HPV16 E7 protein to bind RB and induce DNA synthesis is not sufficient for efficient transforming activity in NIH 3T3 cells. Oncogene 5:1383–1389
    [Google Scholar]
  3. Bannister A. J., Cook A., Kouzarides T. 1991; In vitro DNA binding activity of Fos/Jun and BZLF1 but not C/EBP is affected by redox changes. Oncogene 6:1243–1250
    [Google Scholar]
  4. Barbosa M. S., Edmonds C., Fisher C., Schiller J. T., Lowy D. R., Vousden K. H. 1990; The region of the HPV E7 oncoprotein homologous to adenovirus E1a and SV40 large T antigen contains separate domains for Rb binding and casein kinase II. EMBO Journal 9:153–160
    [Google Scholar]
  5. Clemens K. E., Brent R., Gyuris J., Münger K. 1995; Dimerization of the human papillomavirus E7 oncoprotein in vivo. Virology 214:289–293
    [Google Scholar]
  6. Edmonds C., Vousden K. H. 1989; A point mutational analysis of human papillomavirus type 16 E7 protein. Journal of Virology 63:2650–2656
    [Google Scholar]
  7. Geisberg J. V., Lee W. S., Berk A. J., Ricciardi R. P. 1994; The zinc finger region of the adenovirus E1A transactivating domain complexes with the TATA box binding protein. Proceedings ofthe National Academy of Sciences, USA 91:2488–2492
    [Google Scholar]
  8. Hagemeier C., Walker S., Caswell R., Kouzarides T., Sinclair J. 1992; The human cytomegalovirus 80-kilodalton but not the 72- kilodalton immediate-early protein transactivates heterologous promoters in a TATA box-dependent mechanism and interacts directly with TFIID. Journal of Virology 66:4452–4456
    [Google Scholar]
  9. Hagemeier C., Bannister A. J., Cook A., Kouzarides T. 1993; The activation domain of transcription factor PU.1 binds the retinoblastoma (RB) protein and the transcription factor TFIID in vitro: RB shows sequence similarity to TFIID and TFIIB. Proceedings of the National Academy of Sciences, USA 90:1580–1584
    [Google Scholar]
  10. Hagemeier C., Caswell R., Hayhurst G., Sinclair J., Kouzarides T. 1994; Functional interaction between the HCMV IE2 transactivator and the retinoblastoma protein. EMBO Journal 13:2897–2903
    [Google Scholar]
  11. Kessis T. D., Slebos R. J., Nelson W. G., Kastan M. B., Plunkett B. S., Han S. M., Lorincz A. T., Hedrick L., Cho K. R. 1993; Human papillomavirus 16 E6 expression disrupts the p53-mediated cellular response to DNA damage. Proceedings of the National Academy of Sciences, USA 90:3988–3992
    [Google Scholar]
  12. Lam E. W. F., Morris J. D. H., Davies R., Crook T., Watson R. J., Vousden K. H. 1994; HPV16 E7 oncoprotein deregulates b-myb expression - correlation with targeting of p107/E2F complexes. EMBO Journal 13:871–878
    [Google Scholar]
  13. Lee W. S., Kao C. C., Bryant G. O., Liu X., Berk A. J. 1991; Adenovirus E1A activation domain binds the basic repeat in the TATA box transcription factor. Cell 67:365–376
    [Google Scholar]
  14. Lundblad J. R., Kwok R. P. S., Laurance M. E., Harter M. L., Goodman R. H. 1995; Adenoviral E1A-associated protein p300 as a functional homologue of the transcriptional co-activator CBP. Nature 374:85–88
    [Google Scholar]
  15. McIntyre M. C., Frattini M. G., Grossman S. R., Laimins L. A. 1993; Human papillomavirus type 18 E7 protein requires intact Cys-X- X-Cys motifs for zinc binding, dimerization, and transformation but not for Rb binding. Journal of Virology 67:3142–3150
    [Google Scholar]
  16. Massimi P., Pim D., Storey A., Banks L. 1996; HPV-16 E7 and adenovirus E1a complex formation with TATA box binding protein is enhanced by casein kinase II phosphorylation. Oncogene 12:2325–2330
    [Google Scholar]
  17. Mazzarelli J. M., Atkins G. B., Geisberg J. V., Ricciardi R. P. 1995; The viral oncoproteins Ad5 E1A, HPV16 E7 and SV40 TAg bind a common region of the TBP-associated factor-110. Oncogene 11:1859–1864
    [Google Scholar]
  18. Morris J. D., Crook T., Bandara L. R., Davies R., LaThangue N. B., Vousden K. H. 1993; Human papillomavirus type 16 E7 regulates E2F and contributes to mitogenic signalling. Oncogene 8:893–898
    [Google Scholar]
  19. Rawls J. A., Pusztai R., Green M. 1990; Chemical synthesis of human papillomavirus type 16 E7 oncoprotein: autonomous protein domains for induction of cellular DNA synthesis and for transactivation. Journal of Virology 64:6121–6129
    [Google Scholar]
  20. Scheffner M., Werness B. A., Huibregtse J. M., Leine A. J., Howley P. M. 1990; The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53. Cell 63:1129–1136
    [Google Scholar]
  21. Stirdivant S. M., Huber H. E., Patrick D. R., Defeo-Jones D., McAvoy E. M., Garsky V. M., Oliff A., Heimbrook D. C. 1992; Human papillomavirus type 16 E7 protein inhibits DNA binding by the retinoblastoma gene product. Molecular and Cellular Biology 12:1905–1914
    [Google Scholar]
  22. Vousden K. H. 1994; Interactions between papillomavirus proteins and tumor suppressor gene products. Advances in Cancer Research 64:1–24
    [Google Scholar]
  23. Vousden K. H. 1995; Regulat ion of the cell cycle by viral oncoproteins. Seminars in Cancer Biology 6:109–116
    [Google Scholar]
  24. Wong H. K., Ziff E. B. 1996; The human papillomavirus type 16 E7 protein complements adenovirus type 5 E1A amino-terminus-dependent transactivation of adenovirus type 5 early gene and increases ATF and Oct-1 DNA binding activity. Journal of Virology 70:332–340
    [Google Scholar]
  25. Zwerschke W., Joswig S., Jansen-Dürr P. 1996; Identification of domains required for transcriptional activation and protein dimerization in the human papillomavirus type-16 E7 protein. Oncogene 12:213–220
    [Google Scholar]
/content/journal/jgv/10.1099/0022-1317-78-4-905
Loading
/content/journal/jgv/10.1099/0022-1317-78-4-905
Loading

Data & Media loading...

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