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 Article
  • Published:

Molecular mechanisms of hyperplasia induction by human papillomavirus E7

Abstract

Infections of human papillomavirus (HPV) induce a variety of benign tumors, such as warts and condylomas. During the process of aberrant cell proliferation, genetic mutations are accumulated in the cells, from which malignant tumor cells arise. The viral oncoproteins E6 and E7 are known to help disrupt the cell cycle checkpoint machinery and accelerate chromosomal instability, events which are critical in malignant conversion. However, the mechanisms involved in the hyperplasia caused by HPV infection have remained unknown. We analysed the effects of regulatory genes of HPV18, a typical high-risk-type HPV, on the formation of the epithelial organ by using an organotypic culture system, and found that E7 had potent activity to induce hyperplasia, to which the disruption of the pRb pathway was well correlated. However, analysis with the E7 variants indicated that other pocket proteins are also involved in the activity.

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

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

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

Accession codes

Accessions

GenBank/EMBL/DDBJ

References

  • Baker CC, Phelps WC, Lindgren V, Braun MJ, Gonda MA, Howley PM . (1987). J Virol 61: 962–971.

  • Balsitis SJ, Sage J, Duensing S, Münger K, Jacks T, Lambert P . (2003). Mol Cell Biol 23: 9094–9103.

  • Basile JR, Zacny V, Münger K . (2001). J Biol Chem 276: 22522–22528.

  • Blanton RA, Coltrera MD, Gown AM, Halbert CL, McDougall JK . (1992). Cell Growth Differ 3: 791–802.

  • Boutwell RK . (1989). Prog Clin Biol Res 298: 3–15.

  • Boyer SN, Wazer DE, Band V . (1996). Cancer Res 56: 4620–4624.

  • Chellappan S, Kraus VB, Kroger B, Münger K, Howley PM, Phelps WC et al. (1992). Proc Natl Acad Sci USA 89: 4549–4553.

  • Cheng S, Schmidt-Grimminger D-C, Murant T, Broker TR, Chow LT . (1995). Genes Dev 9: 2335–2349.

  • Chien W-M, Parker JN, Schmidt-Grimminger D-C, Broker TR, Chow LT . (2000). Cell Growth Differ 11: 425–435.

  • Choo KB, Pan CC, Han SH . (1987). Virology 161: 259–261.

  • Classon M, Dyson N . (2001). Exp Cell Res 264: 135–147.

  • Classon M, Harlow E . (2002). Nat Rev Cancer 2: 910–917.

  • Cormack B . (1987) In: Ausubel FM, Brent R, Kingston RE, Moore DD, Seidman JG, Smith JA et al. (eds). Current Protocols in Molecular Biology. John Wiley & Sons, Inc.: New York, pp 8.5.1–8.5.9.

    Google Scholar 

  • Davy CE, Jackson DJ, Wang Q, Raj K, Masterson PJ, Fenner NF et al. (2002). J Virol 76: 9806–9818.

  • Desaintes C, Demeret C, Goyat S, Yaniv M, Thierry F . (1997). EMBO J 16: 504–514.

  • Dollard SC, Wilson JL, Demeter LM, Bonnez W, Reichmann RC, Broker TR et al. (1992). Genes Dev 6: 1131–1142.

  • Dowhanick JJ, McBride AA, Howley PM . (1995). J Virol 69: 7791–7799.

  • Duensing S, Duensing A, Crum CP, Münger K . (2001a). Cancer Res 61: 2356–2360.

  • Duensing S, Duensing A, Flores ER, Do A, Lambert PF, Münger K . (2001b). J Virol 75: 7712–7716.

  • Duensing S, Münger K . (2003). J Virol 77: 12331–12335.

  • Dyson N, Guida P, Münger K, Harlow E . (1992). J Virol 66: 934–937.

  • Dyson N, Howley PM, Münger K, Harlow E . (1989). Science 243: 934–937.

  • Frattini MG, Lim HB, Laimins LA . (1996). Proc Natl Acad Sci USA 93: 3062–3067.

  • Genther Williams SM, Disbrow GL, Schlegel R, Lee D, Threadgill DW, Lambert PF . (2005). Cancer Res 65: 6534–6542.

  • Gonzalez SL, Stremlau M, He X, Basile JR, Münger K . (2001). J Virol 75: 7583–7591.

  • Graña X, Garriga J, Mayol X . (1998). Oncogene 17: 3365–3383.

  • Gulliver GA, Herber RL, Liem A, Lambert PF . (1997). J Virol 71: 5905–5914.

  • Halbert CL, Demers GW, Galloway DA . (1992). J Virol 66: 2125–2134.

  • Heck DV, Yee CL, Howley PM, Münger K . (1992). Proc Natl Acad Sci USA 89: 4442–4446.

  • Helt AM, Funk JO, Galloway DA . (2002). J Virol 76: 10559–10568.

  • Herber R, Liem A, Pitot H, Lambert PF . (1996). J Virol 70: 1873–1881.

  • Howley PM, Lowy D . (2001) In: Knipe D, Howley PM (eds). Fields Virology, vol. 2. Lippincott Williams & Wilkins: Hagerstown, pp 2197–2229.

    Google Scholar 

  • 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.

  • Iwasa H, Han J, Ishikawa F . (2003). Genes Cells 8: 131–144.

  • Jeon S, Lambert PF . (1995). Proc Natl Acad Sci USA 92: 1654–1658.

  • Jones DL, Münger K . (1997). J Virol 71: 2905–2912.

  • Kiyono T, Foster SA, Koop JI, McDougall JK, Galloway DA . (1998). Nature 396: 84–88.

  • Klingelhutz AJ, Foster SA, McDougall JK . (1996). Nature 380: 79–82.

  • Lee JO, Russo AA, Pavletich NP . (1998). Nature 391: 859–865.

  • Lipinski MM, Jacks T . (1999). Oncogene 18: 7873–7882.

  • Majewski S, Jablonska S . (2003). Exp Dermatol 12: 721–728.

  • McCance DJ, Kopan R, Fuchs E, Laimins LA . (1988). Proc Natl Acad Sci USA 85: 7169–7173.

  • Meyers C, Frattini MG, Hudson JB, Laimins LA . (1992). Science 257: 2254–2260.

  • Münger K, Baldwin A, Edwards KM, Hayakawa H, Nguyen CL, Owens M et al. (2004). J Virol 78: 11451–11460.

  • Münger K, Basile J, Duensing S, Eichten A, Gonzalez SL, Grace M et al. (2001). Oncogene 20: 7888–7898.

  • Nakahara T, Nishimura A, Tanaka M, Ueno T, Ishimoto A, Sakai H . (2002). J Virol 76: 10914–10920.

  • Nguyen ML, Nguyen MM, Lee D, Griep AE, Lambert PF . (2003). J Virol 77: 6957–6964.

  • Nishimura A, Ono T, Ishimoto A, Dowhanick JJ, Frizzell MA, Howley PM et al. (2000). J Virol 74: 3752–3760.

  • Pan H, Griep A . (1995). Genes Dev 9: 2157–2169.

  • Pfister H . (2003). J Natl Cancer Inst Monogr 31: 52–56.

  • Ruzinova MB, Benezra R . (2003). Trends Cell Biol 13: 410–418.

  • Sambrool J, Fritsch EF, Maniatis T . (1989a). Molecular Cloning, vol. 3. Cold Spring Harbor Laboratory Press: New York, pp 18.30–18.33.

    Google Scholar 

  • Sambrool J, Fritsch EF, Maniatis T . (1989b). Molecular Cloning, vol. 3. Cold Spring Harbor Laboratory Press: New York, pp 16.33–16.36.

    Google Scholar 

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

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

  • Song S, Pitot HC, Lambert PF . (1999). J Virol 73: 5887–5893.

  • Steenbergen RDM, Parker JN, Isern S, Snijders PJF, Walboomers JMM, Meijer CJLM et al. (1998). J Virol 72: 749–757.

  • Thompsom DA, Zacny V, Belinsky GS, Classon M, Jones DL, Schlegel R et al. (2001). Oncogene 20: 3629–3640.

  • Tsunenaga M, Kohno T, Horii I, Yasumoto S, Huh NH, Tachikawa T et al. (1994). Jpn J Cancer Res 85: 238–244.

  • Zhang B, Chen W, Roman A . (2005). Proc Natl Acad Sci USA 103: 437–442.

  • Zhang JY, Green CL, Tao S, Khavari PA . (2004). Genes Dev 18: 17–22.

  • zur Hausen H . (1996). Biochim Biophys Acta 1288: F55–F78.

Download references

Acknowledgements

This work is supported by the Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan. TU is supported by Research Fellowships for Young Scientists of the Japanese Society for the Promotion of Science (JSPS). KS and SY are supported by the 21st Century COE Program of JSPS. Full-length clones for HPV18 and HPV11 were provided by Dr Peter M Howley. We thank Dr Akiko Nishimura, Dr Yasutoshi Suzuki, Dr Makoto Tsunenaga and Dr Toshio Kuroki for instructions regarding the organotypic raft culture.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to H Sakai.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ueno, T., Sasaki, K., Yoshida, S. et al. Molecular mechanisms of hyperplasia induction by human papillomavirus E7. Oncogene 25, 4155–4164 (2006). https://doi.org/10.1038/sj.onc.1209445

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1209445

Keywords

This article is cited by

Search

Quick links