1887

Abstract

The E6 protein of cancer-associated human papillomavirus type 16 (16E6) binds to p53 and, in association with E6AP, promotes its degradation through the ubiquitin–proteasome pathway. The aim of this work was to develop monoclonal antibodies against 16E6 and to test their effect on the binding of 16E6 to p53 and E6AP, and on the degradation of p53. It was shown that an antibody directed against the N terminus of 16E6 inhibited E6AP-dependent binding to p53 and degradation of p53, whereas two different antibodies directed to the second zinc-binding domain of 16E6 reduced 16E6 E6AP-independent binding to p53 and binding to E6AP but not degradation of p53.

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2005-04-01
2019-12-09
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References

  1. Banks, L., Matlashewski, G. & Crawford, L. ( 1986; ). Isolation of human-p53-specific monoclonal antibodies and their use in the studies of human p53 expression. Eur J Biochem 159, 529–534.[CrossRef]
    [Google Scholar]
  2. Bedell, M. A., Jones, K. H. & Laimins, L. A. ( 1987; ). The E6-E7 region of human papillomavirus type 18 is sufficient for transformation of NIH 3T3 and rat-1 cells. J Virol 61, 3635–3640.
    [Google Scholar]
  3. Choulier, L., Orfanoudakis, G., Robinson, P., Laune, D., Ben Khalifa, M., Granier, C., Weiss, E. & Altschuh, D. ( 2002; ). Comparative properties of two peptide–antibody interactions as deduced from epitope delineation. J Immunol Methods 259, 77–86.[CrossRef]
    [Google Scholar]
  4. Clifford, G. M., Smith, J. S., Plummer, M., Munoz, N. & Franceschi, S. ( 2003; ). Human papillomavirus types in invasive cervical cancer worldwide: a meta-analysis. Br J Cancer 88, 63–73.[CrossRef]
    [Google Scholar]
  5. Cooper, B., Schneider, S., Bohl, J., Jiang, Y., Beaudet, A. & Vande Pol, S. ( 2003; ). Requirement of E6AP and the features of human papillomavirus E6 necessary to support degradation of p53. Virology 306, 87–99.[CrossRef]
    [Google Scholar]
  6. Crook, T., Tidy, J. A. & Vousden, K. H. ( 1991; ). Degradation of p53 can be targeted by HPV E6 sequences distinct from those required for p53 binding and trans-activation. Cell 67, 547–556.[CrossRef]
    [Google Scholar]
  7. Deryckere, F. & Burgert, H. G. ( 1996; ). Early region 3 of adenovirus type 19 (subgroup D) encodes an HLA-binding protein distinct from that of subgroups B and C. J Virol 70, 2832–2841.
    [Google Scholar]
  8. Foster, S. A., Demers, G. W., Etscheid, B. G. & Galloway, D. A. ( 1994; ). The ability of human papillomavirus E6 proteins to target p53 for degradation in vivo correlates with their ability to abrogate actinomycin D-induced growth arrest. J Virol 68, 5698–5705.
    [Google Scholar]
  9. Gewin, L. & Galloway, D. A. ( 2001; ). E box-dependent activation of telomerase by human papillomavirus type 16 E6 does not require induction of c-myc. J Virol 75, 7198–7201.[CrossRef]
    [Google Scholar]
  10. Giovane, C., Trav, G., Briones, A., Lutz, Y., Wasylyk, B. & Weiss, E. ( 1999; ). Targetting of the N-terminal domain of the human papillomavirus type 16 E6 oncoprotein with monomeric ScFvs blocks the E6-mediated degradation of cellular p53. J Mol Recognit 12, 141–152.[CrossRef]
    [Google Scholar]
  11. Green, S., Isseman, I. & Sheer, E. ( 1988; ). A versatile in vivo and in vitro eukaryotic expression vector for protein engineering. Nucleic Acids Res 16, 369.[CrossRef]
    [Google Scholar]
  12. Grm, H. S. & Banks, L. ( 2004; ). Degradation of hDlg and MAGIs by human papillomavirus E6 is E6-AP-independent. J Gen Virol 85, 2815–2819.[CrossRef]
    [Google Scholar]
  13. Herber, R., Liem, A., Pitot, H. & Lambert, P. F. ( 1996; ). Squamous epithelial hyperplasia and carcinoma in mice transgenic for the human papillomavirus type 16 E7 oncogene. J Virol 70, 1873–1881.
    [Google Scholar]
  14. Huibregtse, J. M., Scheffner, M. & Howley, P. M. ( 1993; ). Localization of the E6-AP regions that direct human papillomavirus E6 binding, association with p53, and ubiquitination of associated proteins. Mol Cell Biol 13, 4918–4927.
    [Google Scholar]
  15. Li, X. & Coffino, P. ( 1996; ). High-risk human papillomavirus E6 protein has two distinct binding sites within p53, of which only one determines degradation. J Virol 70, 4509–4516.
    [Google Scholar]
  16. Liu, Y., Chen, J. J., Gao, Q., Dalal, S., Hong, Y., Mansur, C. P., Band, V. & Androphy, E. J. ( 1999; ). Multiple functions of human papillomavirus type 16 E6 contribute to the immortalization of mammary epithelial cells. J Virol 73, 7297–7307.
    [Google Scholar]
  17. Mantovani, F. & Banks, L. ( 2001; ). The human papillomavirus E6 protein and its contribution to malignant progression. Oncogene 20, 7874–7887.[CrossRef]
    [Google Scholar]
  18. Masson, M., Hindelang, C., Sibler, A. P., Schwalbach, G., Trave, G. & Weiss, E. ( 2003; ). Preferential nuclear localization of the human papillomavirus type 16 E6 oncoprotein in cervical carcinoma cells. J Gen Virol 84, 2099–2104.[CrossRef]
    [Google Scholar]
  19. Matlashewski, G., Schneider, J., Banks, L., Jones, N., Murray, A. & Crawford, L. ( 1987; ). Human papillomavirus type 16 DNA cooperates with activated ras in transforming primary cells. EMBO J 6, 1741–1746.
    [Google Scholar]
  20. Pim, D. & Banks, L. ( 1999; ). HPV-18 E6*I protein modulates the E6-directed degradation of p53 by binding to full-length HPV-18 E6. Oncogene 18, 7403–7408.[CrossRef]
    [Google Scholar]
  21. Pim, D., Thomas, M., Javier, R., Gardiol, D. & Banks, L. ( 2000; ). HPV E6 targeted degradation of the discs large protein: evidence for the involvement of a novel ubiquitin ligase. Oncogene 19, 719–725.[CrossRef]
    [Google Scholar]
  22. Ristriani, T., Nomine, Y., Masson, M., Weiss, E. & Trave, G. ( 2001; ). Specific recognition of four-way DNA junctions by the C-terminal zinc-binding domain of HPV oncoprotein E6. J Mol Biol 305, 729–739.[CrossRef]
    [Google Scholar]
  23. Scheffner, M., Werness, B. A., Huibregtse, J. M., Levine, 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.[CrossRef]
    [Google Scholar]
  24. Schwalbach, G., Sibler, A. P., Choulier, L., Deryckere, F. & Weiss, E. ( 2000; ). Production of fluorescent single-chain antibody fragments in Escherichia coli. Protein Expr Purif 18, 121–132.[CrossRef]
    [Google Scholar]
  25. Sibler, A. P., Nordhammer, A., Masson, M., Martineau, P., Trave, G. & Weiss, E. ( 2003; ). Nucleocytoplasmic shuttling of antigen in mammalian cells conferred by a soluble versus insoluble single-chain antibody fragment equipped with import/export signals. Exp Cell Res 286, 276–287.[CrossRef]
    [Google Scholar]
  26. Song, S., Pitot, H. C. & Lambert, P. F. ( 1999; ). The human papillomavirus type 16 E6 gene alone is sufficient to induce carcinomas in transgenic animals. J Virol 73, 5887–5893.
    [Google Scholar]
  27. Vousden, K. H., Doniger, J., DiPaolo, J. A. & Lowy, D. R. ( 1988; ). The E7 open reading frame of human papillomavirus type 16 encodes a transforming gene. Oncogene Res 3, 167–175.
    [Google Scholar]
  28. Walboomers, J. M., Jacobs, M. V., Manos, M. M. & 7 other authors ( 1999; ). Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 189, 12–19.[CrossRef]
    [Google Scholar]
  29. Watanabe, S., Kanda, T. & Yoshiike, K. ( 1989; ). Human papillomavirus type 16 transformation of primary human embryonic fibroblasts requires expression of open reading frames E6 and E7. J Virol 63, 965–969.
    [Google Scholar]
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