1887

Abstract

Human papillomavirus type 58 (HPV-58) is a very common HPV type in eastern Asia. Little is known about its biology and tumorigenesis. In this study, HPV-58 E2 protein (58E2) was found to interact with E7 protein (58E7), and the hinge domain of 58E2 was shown to be responsible for binding to the 58E7 protein. Interestingly, the E2–E7 interaction appears to be HPV type-specific, as we found that the HPV-16 E2 could not bind to the 58E7 protein, and neither did 58E2 interact with HPV-16 E7. The biological consequence(s) of the E2–E7 interaction in HPV-58, especially in viral tumorigenesis, was investigated. Results showed that, through interacting with 58E7, 58E2 prevented E7-induced retinoblastoma protein (pRb) degradation and prolonged the half-life of pRb in cells. Additionally, 58E2 abrogated 58E7-induced cell proliferation. These observations collectively suggest that direct interaction with 58E7 is another mechanism for 58E2 to inhibit 58E7-associated carcinogenesis in addition to regulating expression of the 58E7 gene.

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2012-07-01
2019-10-14
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References

  1. Androphy E. J., Lowy D. R., Schiller J. T.. ( 1987;). Bovine papillomavirus E2 trans-activating gene product binds to specific sites in papillomavirus DNA. . Nature 325:, 70–73. [CrossRef][PubMed]
    [Google Scholar]
  2. Blachon S., Bellanger S., Demeret C., Thierry F.. ( 2005;). Nucleo-cytoplasmic shuttling of high risk human papillomavirus E2 proteins induces apoptosis. . J Biol Chem 280:, 36088–36098. [CrossRef][PubMed]
    [Google Scholar]
  3. Boyer S. N., Wazer D. E., Band V.. ( 1996;). E7 protein of human papilloma virus-16 induces degradation of retinoblastoma protein through the ubiquitin-proteasome pathway. . Cancer Res 56:, 4620–4624.[PubMed]
    [Google Scholar]
  4. Breiding D. E., Sverdrup F., Grossel M. J., Moscufo N., Boonchai W., Androphy E. J.. ( 1997;). Functional interaction of a novel cellular protein with the papillomavirus E2 transactivation domain. . Mol Cell Biol 17:, 7208–7219.[PubMed]
    [Google Scholar]
  5. Chan P. K., Cheung J. L., Cheung T. H., Lo K. W., Yim S. F., Siu S. S., Tang J. W.. ( 2007;). Profile of viral load, integration, and E2 gene disruption of HPV58 in normal cervix and cervical neoplasia. . J Infect Dis 196:, 868–875. [CrossRef][PubMed]
    [Google Scholar]
  6. Chan P. K., Ho W. C., Yu M. Y., Pong W. M., Chan A. C., Chan A. K., Cheung T. H., Wong M. C., To K. F., Ng H. K.. ( 2009;). Distribution of human papillomavirus types in cervical cancers in Hong Kong: current situation and changes over the last decades. . Int J Cancer 125:, 1671–1677. [CrossRef][PubMed]
    [Google Scholar]
  7. Chao A., Jao M. S., Huang C. C., Huang H. J., Cheng H. H., Yang J. E., Hsueh S., Chen T. C., Qiu J. T.. & other authors ( 2011;). Human papillomavirus genotype in cervical intraepithelial neoplasia grades 2 and 3 of Taiwanese women. . Int J Cancer 128:, 653–659. [CrossRef][PubMed]
    [Google Scholar]
  8. Clifford G. M., Smith J. S., Aguado T., Franceschi S.. ( 2003;). Comparison of HPV type distribution in high-grade cervical lesions and cervical cancer: a meta-analysis. . Br J Cancer 89:, 101–105. [CrossRef][PubMed]
    [Google Scholar]
  9. Corden S. A., Sant-Cassia L. J., Easton A. J., Morris A. G.. ( 1999;). The integration of HPV-18 DNA in cervical carcinoma. . Mol Pathol 52:, 275–282. [CrossRef][PubMed]
    [Google Scholar]
  10. de Sanjose S., Quint W. G., Alemany L., Geraets D. T., Klaustermeier J. E., Lloveras B., Tous S., Felix A., Bravo L. E.. & other authors ( 2010;). Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross-sectional worldwide study. . Lancet Oncol 11:, 1048–1056. [CrossRef][PubMed]
    [Google Scholar]
  11. Demeret C., Yaniv M., Thierry F.. ( 1994;). The E2 transcriptional repressor can compensate for Sp1 activation of the human papillomavirus type 18 early promoter. . J Virol 68:, 7075–7082.[PubMed]
    [Google Scholar]
  12. Demeret C., Garcia-Carranca A., Thierry F.. ( 2003;). Transcription-independent triggering of the extrinsic pathway of apoptosis by human papillomavirus 18 E2 protein. . Oncogene 22:, 168–175. [CrossRef][PubMed]
    [Google Scholar]
  13. Doorbar J.. ( 2005;). The papillomavirus life cycle. . J Clin Virol 32: (Suppl. 1), S7–S15. [CrossRef][PubMed]
    [Google Scholar]
  14. Dowhanick J. J., McBride A. A., Howley P. M.. ( 1995;). Suppression of cellular proliferation by the papillomavirus E2 protein. . J Virol 69:, 7791–7799.[PubMed]
    [Google Scholar]
  15. Dyson N., Howley P. M., Münger K., Harlow E.. ( 1989;). The human papilloma virus-16 E7 oncoprotein is able to bind to the retinoblastoma gene product. . Science 243:, 934–937. [CrossRef][PubMed]
    [Google Scholar]
  16. Dyson N., Guida P., Münger K., Harlow E.. ( 1992;). Homologous sequences in adenovirus E1A and human papillomavirus E7 proteins mediate interaction with the same set of cellular proteins. . J Virol 66:, 6893–6902.[PubMed]
    [Google Scholar]
  17. Fiedler M., Müller-Holzner E., Viertler H. P., Widschwendter A., Laich A., Pfister G., Spoden G. A., Jansen-Dürr P., Zwerschke W.. ( 2004;). High level HPV-16 E7 oncoprotein expression correlates with reduced pRb-levels in cervical biopsies. . FASEB J 18:, 1120–1122.[PubMed]
    [Google Scholar]
  18. Gammoh N., Grm H. S., Massimi P., Banks L.. ( 2006;). Regulation of human papillomavirus type 16 E7 activity through direct protein interaction with the E2 transcriptional activator. . J Virol 80:, 1787–1797. [CrossRef][PubMed]
    [Google Scholar]
  19. Gammoh N., Isaacson E., Tomaić V., Jackson D. J., Doorbar J., Banks L.. ( 2009;). Inhibition of HPV-16 E7 oncogenic activity by HPV-16 E2. . Oncogene 28:, 2299–2304. [CrossRef][PubMed]
    [Google Scholar]
  20. Gauthier J. M., Dillner J., Yaniv M.. ( 1991;). Structural analysis of the human papillomavirus type 16-E2 transactivator with antipeptide antibodies reveals a high mobility region linking the transactivation and the DNA-binding domains. . Nucleic Acids Res 19:, 7073–7079. [CrossRef][PubMed]
    [Google Scholar]
  21. Giarrè M., Caldeira S., Malanchi I., Ciccolini F., Leão M. J., Tommasino M.. ( 2001;). Induction of pRb degradation by the human papillomavirus type 16 E7 protein is essential to efficiently overcome p16INK4a-imposed G1 cell cycle arrest. . J Virol 75:, 4705–4712. [CrossRef][PubMed]
    [Google Scholar]
  22. Gonzalez S. L., Stremlau M., He X., Basile J. R., Münger K.. ( 2001;). Degradation of the retinoblastoma tumor suppressor by the human papillomavirus type 16 E7 oncoprotein is important for functional inactivation and is separable from proteasomal degradation of E7. . J Virol 75:, 7583–7591. [CrossRef][PubMed]
    [Google Scholar]
  23. Goodwin E. C., DiMaio D.. ( 2000;). Repression of human papillomavirus oncogenes in HeLa cervical carcinoma cells causes the orderly reactivation of dormant tumor suppressor pathways. . Proc Natl Acad Sci U S A 97:, 12513–12518. [CrossRef][PubMed]
    [Google Scholar]
  24. Grm H. S., Massimi P., Gammoh N., Banks L.. ( 2005;). Crosstalk between the human papillomavirus E2 transcriptional activator and the E6 oncoprotein. . Oncogene 24:, 5149–5164. [CrossRef][PubMed]
    [Google Scholar]
  25. Harper D. M., Franco E. L., Wheeler C. M., Moscicki A. B., Romanowski B., Roteli-Martins C. M., Jenkins D., Schuind A., Costa Clemens S. A., Dubin G..HPV Vaccine Study group ( 2006;). Sustained efficacy up to 4.5 years of a bivalent L1 virus-like particle vaccine against human papillomavirus types 16 and 18: follow-up from a randomised control trial. . Lancet 367:, 1247–1255. [CrossRef][PubMed]
    [Google Scholar]
  26. Ho C. M., Cheng W. F., Chu T. Y., Chen C. A., Chuang M. H., Chang S. F., Hsieh C. Y.. ( 2006;). Human papillomaviral load changes in low-grade squamous intraepithelial lesions of the uterine cervix. . Br J Cancer 95:, 1384–1389. [CrossRef][PubMed]
    [Google Scholar]
  27. Howley P. M., Lowy D. R.. ( 2001;). Papillomaviruses and their replication. . In Fields Virology, , 4th edn., vol. 2, pp. 2197–2230. Edited by Knipe D. M., Howley P. M... Philadelphia, PA:: Lippincott Williams & Wilkins;.
    [Google Scholar]
  28. Li C., Wu M., Wang J., Zhang S., Zhu L., Pan J., Zhang W.. ( 2010;). A population-based study on the risks of cervical lesion and human papillomavirus infection among women in Beijing, People’s Republic of China. . Cancer Epidemiol Biomarkers Prev 19:, 2655–2664. [CrossRef][PubMed]
    [Google Scholar]
  29. Lusky M., Fontane E.. ( 1991;). Formation of the complex of bovine papillomavirus E1 and E2 proteins is modulated by E2 phosphorylation and depends upon sequences within the carboxyl terminus of E1. . Proc Natl Acad Sci U S A 88:, 6363–6367. [CrossRef][PubMed]
    [Google Scholar]
  30. McBride A. A., Howley P. M.. ( 1991;). Bovine papillomavirus with a mutation in the E2 serine 301 phosphorylation site replicates at a high copy number. . J Virol 65:, 6528–6534.[PubMed]
    [Google Scholar]
  31. Münger K., Werness B. A., Dyson N., Phelps W. C., Harlow E., Howley P. M.. ( 1989;). Complex formation of human papillomavirus E7 proteins with the retinoblastoma tumor suppressor gene product. . EMBO J 8:, 4099–4105.[PubMed]
    [Google Scholar]
  32. Onuki M., Matsumoto K., Satoh T., Oki A., Okada S., Minaguchi T., Ochi H., Nakao S., Someya K.. & other authors ( 2009;). Human papillomavirus infections among Japanese women: age-related prevalence and type-specific risk for cervical cancer. . Cancer Sci 100:, 1312–1316. [CrossRef][PubMed]
    [Google Scholar]
  33. Parkin D. M., Louie K. S., Clifford G.. ( 2008;). Burden and trends of type-specific human papillomavirus infections and related diseases in the Asia Pacific region. . Vaccine 26: (Suppl. 12), M1–M16. [CrossRef][PubMed]
    [Google Scholar]
  34. Riley R. R., Duensing S., Brake T., Münger K., Lambert P. F., Arbeit J. M.. ( 2003;). Dissection of human papillomavirus E6 and E7 function in transgenic mouse models of cervical carcinogenesis. . Cancer Res 63:, 4862–4871.
    [Google Scholar]
  35. Romanczuk H., Howley P. M.. ( 1992;). Disruption of either the E1 or the E2 regulatory gene of human papillomavirus type 16 increases viral immortalization capacity. . Proc Natl Acad Sci U S A 89:, 3159–3163. [CrossRef][PubMed]
    [Google Scholar]
  36. Rozen R., Sathish N., Li Y., Yuan Y.. ( 2008;). Virion-wide protein interactions of Kaposi’s sarcoma-associated herpesvirus. . J Virol 82:, 4742–4750. [CrossRef][PubMed]
    [Google Scholar]
  37. Saitoh T., Kuramochi K., Imai T., Takata K., Takehara M., Kobayashi S., Sakaguchi K., Sugawara F.. ( 2008;). Podophyllotoxin directly binds a hinge domain in E2 of HPV and inhibits an E2/E7 interaction in vitro. . Bioorg Med Chem 16:, 5815–5825. [CrossRef][PubMed]
    [Google Scholar]
  38. Sambrook J., Fritsch E. F., Maniatis T.. ( 1989;). Molecular Cloning: a Laboratory Manual, , 2nd edn.. Cold Spring Harbor, NY:: Cold Spring Harbor Laboratory;.
    [Google Scholar]
  39. 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][PubMed]
    [Google Scholar]
  40. Steger G., Ham J., Lefebvre O., Yaniv M.. ( 1995;). The bovine papillomavirus 1 E2 protein contains two activation domains: one that interacts with TBP and another that functions after TBP binding. . EMBO J 14:, 329–340.[PubMed]
    [Google Scholar]
  41. Tan S. H., Leong L. E., Walker P. A., Bernard H. U.. ( 1994;). The human papillomavirus type 16 E2 transcription factor binds with low cooperativity to two flanking sites and represses the E6 promoter through displacement of Sp1 and TFIID. . J Virol 68:, 6411–6420.[PubMed]
    [Google Scholar]
  42. von Knebel Doeberitz M.. ( 2002;). New markers for cervical dysplasia to visualise the genomic chaos created by aberrant oncogenic papillomavirus infections. . Eur J Cancer 38:, 2229–2242. [CrossRef][PubMed]
    [Google Scholar]
  43. You J., Croyle J. L., Nishimura A., Ozato K., Howley P. M.. ( 2004;). Interaction of the bovine papillomavirus E2 protein with Brd4 tethers the viral DNA to host mitotic chromosomes. . Cell 117:, 349–360. [CrossRef][PubMed]
    [Google Scholar]
  44. Zhang W. F., Li J., Kanginakudru S., Zhao W., Yu X., Chen J. J.. ( 2010;). The human papillomavirus type 58 E7 oncoprotein modulates cell cycle regulatory proteins and abrogates cell cycle checkpoints. . Virology 397:, 139–144. [CrossRef][PubMed]
    [Google Scholar]
  45. Zou N., Lin B. Y., Duan F., Lee K. Y., Jin G., Guan R., Yao G., Lefkowitz E. J., Broker T. R., Chow L. T.. ( 2000;). The hinge of the human papillomavirus type 11 E2 protein contains major determinants for nuclear localization and nuclear matrix association. . J Virol 74:, 3761–3770. [CrossRef][PubMed]
    [Google Scholar]
  46. zur Hausen H.. ( 2002;). Papillomaviruses and cancer: from basic studies to clinical application. . Nat Rev Cancer 2:, 342–350. [CrossRef][PubMed]
    [Google Scholar]
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