Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Paper
  • Published:

Chimaeric HPV E6 proteins allow dissection of the proteolytic pathways regulating different E6 cellular target proteins

Oncogene volume 21, pages 8140–8148 (2002)Cite this article

Abstract

The ability of HPV E6 oncoproteins to induce the degradation of PDZ domain-containing MAGUK proteins correlates with their malignant potential. We previously showed that the HPV-6 E6 protein, when provided with the PDZ-binding domain from HPV-18 E6, acquires the ability to bind the Discs Large (Dlg) tumour suppressor and target it for degradation. Based on this finding we have extended this analysis to E6 proteins from a variety of different papillomavirus types. Cloning a PDZ-binding sequence onto the C-terminus of E6 proteins derived from low-risk mucosal, and low and high-risk cutaneous papillomavirus types, enables them to bind Dlg and a second MAGUK family member, MAGI-1. This renders the mucosally-derived low-risk chimaeric HPV E6 proteins capable of targeting Dlg for degradation, but they are unable to induce significant levels of degradation of MAGI-1. In contrast, none of the E6 proteins derived from cutaneous papillomavirus types induce significant degradation of either MAGI-1 or Dlg when provided with a PDZ-binding domain. These results demonstrate significant differences, both between mucosal and cutaneous HPV E6 proteins and in the pathways required for Dlg and MAGI-1 degradation.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7

Similar content being viewed by others

References

  • Barnes W, Delgado G, Kurman RJ, Petrilli ES, Smith DM, Ahmed S, Lorincz AT, Temple GF, Jenson AB, Lancaster WD . 1988 Gynecol. Oncol. 29: 267–273

  • Be X, Hong Y, Wei J, Androphy EJ, Chen JJ, Baleja JD . 2001 Biochemistry 40: 1293–1299

  • Bilder D, Li M, Perrimon N . 2000 Science 289: 113–116

  • Burnett AF, Barnes WA, Johnson JC, Grendys E, Willett GD, Barter JF, Doniger J . 1992 Gynecol. Oncol. 47: 343–347

  • Craven SE, Bredt DS . 1998 Cell 93: 495–498

  • Das K, Bohl J, Vande Pol SB . 2000 J. Virol. 74: 812–816

  • Dobrosotskaya I, Guy RK, James GL . 1997 J. Biol. Chem. 272: 31589–31597

  • Elbel M, Carl S, Spaderna S, Iftner T . 1997 Virology 239: 132–149

  • Fanning AS, Anderson JM . 1999 J. Clin. Invest. 103: 767–772

  • Gao Q, Kumar A, Singh L, Huibregtse JM, Beaudenon S, Srinivasan S, Wazer DE, Band H, Band V . 2002 Cancer Res. 62: 3315–3321

  • Gardiol D, Banks L . 1998 J. Gen. Virol. 79: 1963–1970

  • Gardiol D, Kühne K, Glaunsinger B, Lee SS, Javier R, Banks L . 1999 Oncogene 18: 5487–5496

  • Glaunsinger BA, Lee SS, Thomas M, Banks L, Javier R . 2000 Oncogene 19: 5270–5280

  • Goode S, Perrimon N . 1997 Genes Dev. 11: 2532–2544

  • Huibregtse JM, Scheffner M, Howley PM . 1991 EMBO J. 10: 4129–4135

  • Huibregtse JM, Scheffner M, Howley PM . 1993 Mol. Cell Biol. 13: 775–784

  • Inoue T, Oka K, Yong-II H, Vousden KH, Kyo S, Jing P, Hakura A, Yutsoda M . 1998 Mol. Carcin. 21: 215–222

  • Ishiwatari H, Hayasaka N, Inoue H, Yutsudo M, Hakura A . 1994 J. Med. Virol. 44: 243–249

  • Jackson S, Harwood C, Thomas M, Banks L, Storey A . 2000 Genes Dev. 14: 3065–3073

  • Kiyono T, Hiraiwa A, Fujita M, Hayashi Y, Akiyama T, Ishibashi M . 1997 Proc. Natl. Acad. Sci. USA 94: 11612–11616

  • Kurman RJ, Schiffman MH, Lancaster WD, Reid R, Jenson AB, Temple GF, Lorincz AT . 1988 Am. J. Obstet. Gynecol. 159: 293–296

  • Lee S, Weiss R, Javier R . 1997 Proc. Natl. Acad. Sci. USA 94: 6670–6675

  • Lee S, Glaunisinger B, Mantovani F, Banks L, Javier R . 2000 J. Virol. 74: 9680–9693

  • Liu Y, Chen JJ, Gao Q, Dalal S, Hong Y, Mansur CP, Band V, Androphy E . 1999 J. Virol. 73: 7297–7307

  • Lue RL, Marfatia SM, Branton D, Chisti HA . 1994 Proc. Natl. Acad. Sci. USA 91: 9818–9822

  • Mantovani F, Banks L . 2001 Oncogene 20: 7874–7887

  • Nakagawa S, Watanabe S, Yoshikawa H, Taketani Y, Yoshiike K, Kanda T . 1995 Virology 212: 535–542

  • Nakagawa S, Huibregtse JM . 2000 Mol. Cell. Biol. 20: 8244–8253

  • Petersen B, Buchwald C, Gerstoft J, Bretlau P, Lindeberg H . 1998 J. Laryngol. Otol. 112: 1101–1104

  • Pim D, Thomas M, Javier R, Gardiol D, Banks L . 2000 Oncogene 19: 719–725

  • Pim D, Storey A, Thomas M, Massimi P, Banks L . 1994 Oncogene 9: 1869–1876

  • Ponting CP, Phillips C, Davies KE, Blake DJ . 1997 Bioessays 19: 469–479

  • Querido E, Blanchette P, Yan Q, Kamura T, Morrison M, Boivin D, Kaelin W, Conaway R, Weliky Conaway J, Branton P . 2001 Genes Dev. 15: 3104–3117

  • Rady P, Schnadig V, Weiss R, Hughes T, Tyring S . 1998 Laryngoscope 108: 735–740

  • Rabah R, Lancaster W, Thomas R, Gregoire L . 2001 Pediatr. Dev. Pathol. 4: 68–72

  • Saras J, Heldin CH . 1996 Trends Biochem. Sci. 21: 455–458

  • Scheffner M, Werness BA, Huibregste JM, Levine AJ, Howley PM . 1990 Cell 63: 1129–1136

  • Scheffner M, Münger K, Huibregtse JM, Howley PM . 1992 EMBO J. 11: 2425–2431

  • Scheffner M, Huibregtse JM, Viestra RD, Howley PM . 1993 Cell 75: 495–505

  • Smith DB, Johnson KS . 1988 Gene 67: 31–40

  • Thomas M, Pim D, Banks L . 1999 Oncogene 18: 7690–7700

  • Thomas M, Glaunsinger B, Pim D, Javier R, Banks L . 2001 Oncogene 20: 5431–5439

  • Thomas M, Laura R, Hepner K, Guccione E, Sawyers C, Lasky L, Banks L . 2002 Oncogene 21: 5088–5096

  • Werness BA, Levine AJ, Howley PM . 1990 Science 248: 76–79

  • Woods DF, Hough C, Peel D, Callaini G, Bryant PJ . 1996 J. Cell Biol. 134: 1469–1482

  • Zhang J, Rose BR, Thompson CH, Jarrett C, Russell P, Houghton RS, Cossart YE . 1995 Gynecol. Oncol. 57: 170–177

Download references

Acknowledgements

We thank the following for their kind gifts of papillomavirus E6 open reading frames: Janet Brandsma for CRPV, Elliot Androphy for BPV-1, John Doorbar for HPV-1, Herbert Pfister for HPV-8 and Lou Laimins for HPV-31. This work was supported in part by a research grant from the Associazione Italiana per la Ricerca sul Cancro.

Author information

Authors and Affiliations

  1. International Centre for Genetic Engineering and Biotechnology, Area Science Park, Padriciano-99, I-34012, Trieste, Italy

    David Pim, Miranda Thomas & Lawrence Banks

Authors
  1. David Pim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Miranda Thomas
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lawrence Banks
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to David Pim.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pim, D., Thomas, M. & Banks, L. Chimaeric HPV E6 proteins allow dissection of the proteolytic pathways regulating different E6 cellular target proteins. Oncogene 21, 8140–8148 (2002). https://doi.org/10.1038/sj.onc.1206026

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1206026

Keywords

This article is cited by

Search

Advanced search

Quick links