1887

Abstract

E5 is the smallest transforming protein encoded by the human papillomaviruses (HPVs). It has been shown to promote anchorage-independent growth in established NIH 3T3 cells, an activity that is enhanced in the presence of epidermal growth factor (EGF). It is thought that this activity of E5 is brought about by an increase in the half-life of stimulated EGF receptors, possibly through the perturbation of receptor processing. Recent studies have also shown that E5 can co-operate with HPV-16 E7 to stimulate proliferation of primary rodent cells. Using haemagglutinin I epitope-tagged E5 proteins, we have compared the mitogenic activity of HPV-6 and HPV-16 E5. Both tagged proteins retain the ability to bind to the cellular 16 kDa H-ATPase protein. In addition, both HPV-6 and HPV-16 E5 retain the ability to co-operate with E7 in primary rodent cells, although HPV-16 E5 is considerably more active than HPV-6 E5 in these mitogenic assays. Interestingly, transfection of a plasmid over-expressing c-Raf appears to be capable of functionally substituting for E5 in the co-mitogen assays. Polyclonal cell lines derived from baby rat kidney cells co-transfected with E7 and E5 genes continue to express both the E5 and E7 mRNA, although the level of E5 expression is very low and protein cannot be detected. These polyclonal lines appear to be immortal and in some cases demonstrate anchorage-independent growth, an activity which is enhanced by the addition of EGF.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-76-5-1239
1995-05-01
2024-03-28
Loading full text...

Full text loading...

/deliver/fulltext/jgv/76/5/JV0760051239.html?itemId=/content/journal/jgv/10.1099/0022-1317-76-5-1239&mimeType=html&fmt=ahah

References

  1. Androphy E. J., Hubbert N. L., Schiller J. T., Lowy D. R. 1987; Identification of the HPV-16 E6 protein from transformed mouse cells and human cervical carcinoma cell lines. EMBO Journal 6:989–992
    [Google Scholar]
  2. Banks L., Spence P., Androphy E., Hubbert N., Matlashewski G., Murray A., Crawford L. 1987; Identification of the human papillomavirus type 18 E6 polypeptide in cells derived from cervical carcinomas. Journal of General Virology 68:1351–1359
    [Google Scholar]
  3. Bouvard V., Matlashewski G., Gu Z.-M., Storey A., Banks L. 1994; The human papillomavirus type 16 E5 gene co-operates with the E7 gene to stimulate proliferation of primary cells and increases viral gene expression. Virology 203:73–80
    [Google Scholar]
  4. Cohen B. D., Goldstein D. J., Rutledge L., Vass W. C., Lowy D. R., Schlegel R., Schiller J. T. 1993; Transformation-specific interaction of bovine papillomavirus E5 oncoprotein with platelet-derived growth factor receptor transmembrane domain and the epidermal growth factor cytoplasmic domain. Journal of Virology 67:5303–5311
    [Google Scholar]
  5. Conrad M., Bubb V. J., Schlegel R. 1993; The human papillomavirus type 6 and 16 E5 proteins are membrane-associated proteins which associate with the 16-Kilodalton pore-forming protein. Journal of Virology 67:6170–6178
    [Google Scholar]
  6. Crook T., Storey A., Almond K., Crawford L. 1988; Human papillomavirus type 16 cooperates with activated ras and fos oncogenes in the hormone-dependent transformation of primary mouse cells. Proceedings of the National Academy of Sciences, USA 85:8820–8824
    [Google Scholar]
  7. DiMaio D., Guralski D., Schiller J. T. 1986; Translation of open reading frame E5 of bovine papillomavirus is required for its transforming activity. Proceedings of the National Academy of Sciences, USA 83:1797–1801
    [Google Scholar]
  8. Dürst M., Gissmann L., Ikenberg H., Zur Hausen H. 1983; A papillomavirus DNA from a cervical carcinoma and its prevalence in cancer biopsy samples from different geographic regions. Proceedings of the National Academy of Sciences, USA 80:3812–3815
    [Google Scholar]
  9. Gillespie G. A., Somolo S., Germino G. G., Weinstat-Saslow D., Reeders S. T. 1991; CpG island in the region of an autosomal dominant polycystic kidney disease locus defines the 5′ end of a gene encoding a putative proton channel. Proceedings of the National Academy of Sciences, USA 88:4289–4293
    [Google Scholar]
  10. Gissmann L., Wolnick L., Ikenberg H., Koldovsky V., Schnurch H. G., Zur Hausen H. 1983; Human papillomavirus types 6 and 11 DNA sequences in genital and laryngeal papillomas and in some cervical cancers. Proceedings of the National Academy of Sciences, USA 80:560–563
    [Google Scholar]
  11. Goldstein D. J., Schlegel R. 1990; The E5 oncoprotein of bovine papillomavirus binds to a 16 kd cellular protein. EMBO Journal 9:137–146
    [Google Scholar]
  12. Goldstein D. J., Finbow M. E., Andresson T., McLean P., Smith K., Bubb V., Schlegel R. 1991; Bovine papillomavirus E5 oncoprotein binds to the 16K component of vacuolar H+-ATPases. Nature 352:347–349
    [Google Scholar]
  13. Goldstein D. J., Andresson T., Sparkowski J. J., Schlegel R. 1992; The BPV-1 E5 protein, the 16 KDa membrane pore-forming protein and the PDGF receptor exist in a complex that is dependent on hydrophobic transmembrane interactions. EMBO Journal 11:4851–4859
    [Google Scholar]
  14. Leechanachai P., Banks L., Moreau F., Matlashewski G. 1992; The E5 gene from human papillomavirus type 16 is an oncogene which enhances growth factor-mediated signal transduction to the nucleus. Oncogene 1:19–25
    [Google Scholar]
  15. Martin P., Vass W. C., Schiller J. T., Lowy D. R., Velu T. J. 1989; The bovine papillomavirus E5 transforming protein can stimulate the transforming activity of EGF and CSF receptors. Cell 59:21–32
    [Google Scholar]
  16. Matlashewski G., Schneider J., Banks L., Jones N., Murray A., Crawford L. 1987; Fluman papillomavirus type 16 DNA cooperates with activated ras in transforming primary cells. EMBO Journal 6:1741–1746
    [Google Scholar]
  17. 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]
  18. Petti L., DiMaio D. 1994; Specific interaction between the bovine papillomavirus E5 transforming protein and the β receptor for platelet-derived growth factor in stably transformed and acutely transfected cells. Journal of Virology 68:3582–3592
    [Google Scholar]
  19. Petti L., Nilson N. A., DiMaio D. 1991; Activation of platelet-derived growth factor receptor by the bovine papillomavirus E5 transforming protein. EMBO Journal 10:845–855
    [Google Scholar]
  20. Phelps W. C., Yee C. L., Münger K., Howley P. M. 1988; The human papillomavirus type 16 E7 gene encodes transactivation and transformation functions similar to those of adenovirus E1A. Cell 53:539–547
    [Google Scholar]
  21. Pim D., Collins M., Banks L. 1992; Human papillomavirus type 16 E5 gene stimulates the transforming activity of the epidermal growth factor receptor. Oncogene 7:27–32
    [Google Scholar]
  22. Schiller J. T., Vass W. C., Lowy D. R. 1984; Identification of a second transforming region in bovine papillomavirus DNA. Proceedings of the National Academy of Sciences, USA 81:7880–7884
    [Google Scholar]
  23. Schiller J. T., Vass W. C., Vousden K. H., Lowy D. R. 1986; The E5 open reading frame of bovine papillomavirus type 1 encodes a transforming gene. Journal of Virology 57:1–6
    [Google Scholar]
  24. Schwarz E., Freese U. K., Gissmann L., Mayer W., Roggenbuck B., Stremlau A., Zur Hausen H. 1985; Structure and transcription of human papillomavirus sequences in cervical carcinoma cells. Nature 314:111–114
    [Google Scholar]
  25. Smith M. R., Degudicibus S. J., Stacey D. W. 1986; Requirement for c-ras proteins during viral oncogene transformation. Nature 320:540–543
    [Google Scholar]
  26. Smotkin D., Wettstein F. O. 1987; The major human papillomavirus protein in cervical cancers is a cytoplasmic phosphoprotein. Journal of Virology 61:1686–1689
    [Google Scholar]
  27. Southern E. M. 1975; Detection of specific sequences among DNA fragments separated by gel electrophoresis. Journal of Molecular Biology 98:503–517
    [Google Scholar]
  28. Storey A., Banks L. 1993; Human papillomavirus type 16 E6 gene co-operates with EJ-ras to immortalise primary mouse cells. Oncogene 8:919–924
    [Google Scholar]
  29. Storey A., Pim D., Murray A., Osborn K., Banks L., Crawford L. 1988; Comparison of the in vitro transforming activities of human papillomavirus types. EMBO Journal 7:1815–1820
    [Google Scholar]
  30. 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]
  31. Straight S. W., Hinkle P. M., Jewers R. I., McCance D. J. 1993; The E5 oncoprotein of human papillomavirus type 16 transforms fibroblasts and alfects the down regulation of the epidermal growth factor receptor in keratinocytes. Journal of Virology 67:4521–4532
    [Google Scholar]
  32. Wilkinson D., De Vries R. R. P., Madrigal J. A., Lock C. B., Morgenstern J. P., Trowsdale J., Altmann D. M. 1988; Analysis of HLA-DR glycoproteins by DNA-mediated gene transfer. Journal of Experimental Medicine 146:1442–1458
    [Google Scholar]
  33. Wilson I. A., Niman H. L., Houghten R. A., Cherenson A. R., Connolly M. L., Lerner R. A. 1984; The structure of an antigenic determinant in a protein. Cell 37:767–778
    [Google Scholar]
  34. Yang Y.-C., Okayama H., Howley P. M. 1985; Bovine papillomavirus contains multiple transforming genes. Proceedings of the National Academy of Sciences, USA 82:1030–1034
    [Google Scholar]
  35. Yee C., Hewlett I. K., Baker C. C., Schlegel R., Howley P. M. 1985; Presence and expression of human papillomavirus sequences in human cervical carcinoma cell lines. American Journal of Pathology 119361–366
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-76-5-1239
Loading
/content/journal/jgv/10.1099/0022-1317-76-5-1239
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