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E7 Protein

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Papillomaviruses in Human Cancer

Abstract

The first evidence for an involvement of the E7 protein in malignant transformation came from studies on HPV-infected cells. In several cervical carcinoma-derived cell lines, such as SiHa, CaSki and HeLa, the HPV DNA is integrated in the cellular genome as single or multiple copies. This viral DNA integration results in the disruption of several viral genes with consistent preservation of only the early E6 and E7 genes (for more detail see chapter 2). The involvement of the E7 protein in immortalization and transformation of the host cell was confirmed by a number of in vitro assays and by transgenic mouse models. Biochemical studies have provided further evidence that the E7 protein is directly involved in the induction of immortalization and malignant transformation of the host cells. E7 proteins from the “high risk” HPV types have the ability to interact with and alter the function of a number of cellular proteins which play a key role in controlling the proliferative program of the cell.

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References

  1. Smotkin D, Wettstein FO. The major human papillomavirus protein in cervical cancers is a cytoplasmic phosphoprotein. J Virol 1987; 61: 1686–9.

    PubMed  CAS  Google Scholar 

  2. Armstrong DJ, Roman A. Mutagenesis of human papillomavirus types 6 and 16 E7 open reading frames alters the electrophoretic mobility of the expressed proteins. J Gen Virol 1992; 73: 1275–9.

    Article  PubMed  CAS  Google Scholar 

  3. Armstrong DJ, Roman A. The anomalous electrophoretic behavior of the human papillomavirus type 16 E7 protein is due to the high content of acidic amino acid residues. Biochem Biophys Res Commun 1993; 192: 1380–7.

    Article  PubMed  CAS  Google Scholar 

  4. Sang BC, Barbosa MS. Single amino acid substitutions in “low-risk” human papillomavirus (HPV) type 6 E7 protein enhance features characteristic of the “high-risk” HPV E7 oncoproteins. Proc Natl Acad Sci USA 1992; 89: 8063–7.

    Article  PubMed  CAS  Google Scholar 

  5. Vousden KH, Jat PS. Functional similarity between HPV16E7, SV40 large T and adenovirus Ela proteins. Oncogene 1989; 4: 153–8.

    PubMed  CAS  Google Scholar 

  6. Phelps WC, Yee CL, Munger K et al. The human papillomavirus type 16 E7 gene encodes transactivation and transformation functions similar to those of adenovirus E1A. Cell 1988; 53: 539–547.

    Article  PubMed  CAS  Google Scholar 

  7. Davies RC, Vousden KH. Functional analysis of human papillomavirus type 16 E7 by complementation with adenovirus E1A mutants. J Gen Virol 1992; 73: 2135–9.

    Article  PubMed  CAS  Google Scholar 

  8. Ikeda MA, Nevins JR. Identification of distinct roles for separate E1A domains in disruption of E2F complexes. Mol and Cell Biol 1993; 13: 7029–7035.

    CAS  Google Scholar 

  9. Fattaey AR, Harlow E, Helin K. Independent regions of adenovirus E1A are required for binding to and dissociation of E2F-protein complexes. Mol and Cell Biol 1993; 13: 7267–7277.

    CAS  Google Scholar 

  10. Whyte P, Williamson NW, Harlow E. Cellular targets for transformation by the adenovirus E1A proteins. Cell 1989; 56: 67–75.

    Article  PubMed  CAS  Google Scholar 

  11. Banks L, Edmonds C, Vousden K. Ability of the HPV16 E7 protein to bind RB and induce DNA synthesis is not sufficient for efficient transforming activity in NIH3T3 cells. Oncogene 1990; 5: 1383–1389.

    PubMed  CAS  Google Scholar 

  12. Phelps WC, Munger K, Yee CL et al. Structure-function analysis of the human papillomavirus type 16 E7 oncoprotein. J Virol 1992; 66: 2418–2427.

    PubMed  CAS  Google Scholar 

  13. Watanabe S, Kanda T, Sato H et al. Mutational analysis of human papillomavirus type 16 E7 functions. J Virol 1990; 64: 207–214.

    PubMed  CAS  Google Scholar 

  14. Zerfass K, Schulze A, Spitkovsky D et al. Sequential activation of cyclin E and cyclin A gene expression by HPV-16 E7 through sequences necessary for transformation. J Virol 1995; 69: 6389–6399.

    CAS  Google Scholar 

  15. Demers WG, Espling E, Beth Harry J et al. Abrogation of growth arrest signals by human papillomavirus type 16 E7 is mediated by sequences required for transformation. J Virology 1996; 70: 6862–6869.

    PubMed  CAS  Google Scholar 

  16. Dyson N, Howley PM, Munger K et al. The human papilloma virus-16 E7 oncoprotein is able to bind to the retinoblastoma gene product. Science 1989; 243: 934–937.

    Article  PubMed  CAS  Google Scholar 

  17. Davies R, Hicks R, Crook T et al. Human papillomavirus type-16 E7 associates with a histone H1 kinase and with p107 through sequences necessary for transformation. J Virol 1993; 67: 2521–2528.

    PubMed  CAS  Google Scholar 

  18. Hu TH, Ferril SC, Snider AM et al. In vivo analysis of HPV E7 protein association with pRb, p107 and p130. Int J Oncol 1995; 6: 167–174.

    PubMed  CAS  Google Scholar 

  19. Woodworth CD, Doniger J, DiPaolo JA. Immortalisation of human foreskin keratinocytes by various human papillomavirus DNAs corresponds to their association with cervical carcinoma. J Virol 1989; 63: 159–64.

    PubMed  CAS  Google Scholar 

  20. Barbosa MS, Edmonds C, Fisher C et al. The region of the HPV E7 oncoprotein homologous to adenovirus Ela and Sv40 large T antigen contains separate domains for Rb binding and casein kinase II phosphorylation. Embo J 1990; 9: 153–60.

    PubMed  CAS  Google Scholar 

  21. Munger K, Werness BA, Dyson N et al. Complex formation of human papillomavirus E7 proteins with the retinoblastoma tumor suppressor gene product. Embo J 1989; 8: 4099–105.

    PubMed  CAS  Google Scholar 

  22. Heck DV, Yee CL, Howley PM et al. Efficiency of binding the retinoblastoma protein correlates with the transforming capacity of the E7 oncoproteins of the human papillomaviruses. Proc Natl Acad Sci USA 1992; 89: 4442–6.

    Article  PubMed  CAS  Google Scholar 

  23. Yamashita T, Segawa K, Fujinaga Y et al. Biological and biochemical activity of E7 genes of the cutaneous human papillomavirus type 5 and 8. Oncogene 1993; 8: 2433–41.

    PubMed  CAS  Google Scholar 

  24. Schmitt A, Harry JB, Rapp B et al. Comparison of the properties of the E6 and E7 genes of low-and high-risk cutaneous papillomaviruses reveals strongly transforming and high Rb-binding activity for the E7 protein of the low-risk human papillomavirus type 1. J Virol 1994; 68: 7051–7059.

    PubMed  CAS  Google Scholar 

  25. Jones RE, Wegrzyn RJ, Patrick DR et al. Identification of HPV-16 E7 peptides that are potent antagonists of E7 binding to the retino-blastoma suppressor protein. J Biol Chem 1990; 265: 12782–5.

    PubMed  CAS  Google Scholar 

  26. Patrick DR, Oliff A, Heimbrook DC. Identification of a novel retinoblastoma gene product binding site on human papillomavirus type 16 E7 protein. J Biol Chem 1994; 269: 6842–6850.

    PubMed  CAS  Google Scholar 

  27. Firzlaff JM, Galloway DA, Eisenman RN et al. The E7 protein of human papillomavirus type 16 is phosphorylated by casein kinase II. New Biol 1989; 1: 44–53.

    PubMed  CAS  Google Scholar 

  28. Firzlaff JM, Luscher B, Eisenman RN. Negative charge at the casein kinase II phosphorylation site is important for transformation but not for Rb protein binding by the E7 protein of human papillomavirus type 16. Proc Natl Acad Sci USA 1991; 88: 5187–91.

    Article  PubMed  CAS  Google Scholar 

  29. Massimi P, Pim D, Storey A et al. HPV-16 E7 and adenovirus Ela complex formation with TATA box binding protein is enhanced by casein kinase II phosphorylation. Oncogene 1996; 12: 2325–2330.

    PubMed  CAS  Google Scholar 

  30. Culp JS, Webster LC, Friedman DJ et al. The 289-amino acid E1A protein of adenovirus binds zinc in a region that is important for trans-activation. Proc Natl Acad Sci USA 1988; 85: 6450–4.

    Article  PubMed  CAS  Google Scholar 

  31. Barbosa MS, Lowy DR, Schiller JT. Papillomavirus polypeptides E6 and E7 are zinc-binding proteins. J Virol 1989; 63: 1404–7.

    PubMed  CAS  Google Scholar 

  32. Patrick DR, Zhang K, Defeo JD et al. Characterization of functional HPV-16 E7 protein produced in Escherichia coli. J Biol Chem 1992; 267: 6910–5.

    PubMed  CAS  Google Scholar 

  33. McIntyre MC, Frattini MG, Grossman SR et al. Human papillomavirus type-18 E7 protein requires intact Cys-X-X-Cys motifs for zinc binding, dimerization, and transformation but not for Rb binding. J Virol 1993; 67: 3142–3150.

    PubMed  CAS  Google Scholar 

  34. Clemens KE, Brent R, Gyuris J et al. Dimerization of the human papillomavirus E7 oncoprotein in vivo. Virology 1995; 214: 289–293.

    Article  PubMed  CAS  Google Scholar 

  35. Zwerschke W, Joswig S, Jansen-Dürr P. Identification of domains required for transcriptional activation and protein dimerization in the human papillomavirus type-16 E7 protein. Oncogene 1996; 12: 213–220.

    PubMed  CAS  Google Scholar 

  36. Watanabe S, Sato H, Furuno A et al. Changing the spacing between metal-binding motifs decreases stability and transforming activity of the human papillomavirus type 18 E7 oncoprotein. Virology 1992; 190: 872–5.

    Article  PubMed  CAS  Google Scholar 

  37. Sato H, Watanabe S, Furuno A et al. Human papillomavirus type 16 E7 protein expressed in Escherichia coli and monkey COS-1 cells: immunofluorescence detection of the nuclear E7 protein. Virology 1989; 170: 311–5.

    Article  PubMed  CAS  Google Scholar 

  38. Meneguzzi G, Cerni C, Kieny MP et al. Immunization against human papillomavirus type 16 tumor cells with recombinant vaccinia viruses expressing E6 and E7. Virology 1991; 181: 62–9.

    Article  PubMed  CAS  Google Scholar 

  39. Kanda T, Zanma S, Watanabe S et al. Two immunodominant regions of the human papillomavirus type 16 E7 protein are masked in the nuclei of monkey COS-1 cells. Virology 1991; 182: 723–31.

    Article  PubMed  CAS  Google Scholar 

  40. Fujikawa K, Furuse M, Uwabe KI et al. Nuclear localization and transforming activity of human papillomavirus type 16 E7–1-galactosidase fusion protein: Characterization of the nuclear localization sequence. Virology 1994; 204: 789–793.

    Article  PubMed  CAS  Google Scholar 

  41. Tommasino M, Contorni M, Scarlato V et al. Synthesis, phosphorylation, and nuclear localization of human papillomavirus E7 protein in Schizosaccharomyces pombe. Gene 1990; 93: 265–70.

    Article  PubMed  CAS  Google Scholar 

  42. Zatsepina O, Braspenning J, Robberson D et al. The human papillomavirus type E7 protein is associated with the nucleoulus in mammalian and yeast cells. Oncogene 1997; 14: 1137–1145.

    Article  PubMed  CAS  Google Scholar 

  43. Greenfield I, Nickerson J, Penman S et al. Human papillomavirus 16 E7 protein is associated with the nuclear matrix. Proc Natl Acad Sci USA 1991; 88: 11217–21.

    Article  PubMed  CAS  Google Scholar 

  44. Bedell MA, Jones KH, Grossman SR et al. Identification of human papillomavirus type 18 transforming genes in immortalized and primary cells. J Virol 1989; 63: 1247–55.

    PubMed  CAS  Google Scholar 

  45. Kanda T, Watanabe S, Yoshiike K. Immortalization of primary rat cells by human papillomavirus type 16 subgenomic DNA fragments controlled by the SV40 promoter. Virology 1988; 165: 321–5.

    Article  PubMed  CAS  Google Scholar 

  46. Barbosa MS, Vass WC, Lowy DR et al. In vitro biological activities of the E6 and E7 genes vary among human papillomaviruses of different oncogenic potential. J Virol 1991; 65: 292–8.

    PubMed  CAS  Google Scholar 

  47. Le JY, Defendi V. A viral-cellular junction fragment from a human papillomavirus type 16-positive tumor is competent in transformation of NIH 3T3 cells. J Virol 1988; 62: 4420–6.

    PubMed  CAS  Google Scholar 

  48. Yutsudo M, Okamoto Y, Hakura A. Functional dissociation of transforming genes of human papillomavirus type 16. Virology 1988; 166: 594–7.

    Article  PubMed  CAS  Google Scholar 

  49. Tsao YP, Chu TY, Chen TM et al. Effects of E5a and E7 genes of human papillomavirus type 11 on immortalized human epidermal keratinocytes and NIH 3T3 cells. Arch Virol 1994; 138: 177–85.

    Article  PubMed  CAS  Google Scholar 

  50. Ciccolini F, Di Pasquale G, Carlotti F et al. Functional studies of E7 proteins from different HPV types. Oncogene 1994; 9: 2342–2348.

    Google Scholar 

  51. Matlashewski G, Schneider J, Banks L et al. Human papillomavirus type 16 DNA cooperates with activated ras in transforming primary cells. Embo J 1987; 6: 1741–6.

    PubMed  CAS  Google Scholar 

  52. Storey A, Pim D, Murray A et al. Comparison of the in vitro transforming activities of human papillomavirus types. Embo J 1988; 7: 1815–20.

    PubMed  CAS  Google Scholar 

  53. Peacock JW, Matlashewski GJ, Benchimol S. Synergism between pairs of immortalizing genes in transformation assays of rat embryo fibroblasts. Oncogene 1990; 5: 1769–74.

    PubMed  CAS  Google Scholar 

  54. Crook T, Fisher C, Vousden KH. Modulation of immortalizing properties of human papillomavirus type 16 E7 by p53 expression. J Virol 1991; 65: 505–510.

    PubMed  CAS  Google Scholar 

  55. Crook T, Storey A, Almond N et al. Human papillomavirus type 16 cooperates with activated ras ans fos oncogenes in the hormone dependent transformation of primary mouse cells. Proc Natl Acad Sci USA 1988; 85: 8820–8824.

    Article  PubMed  CAS  Google Scholar 

  56. Storey A, Osborn K, Crawford L. Co-transformation by human papillomavirus types 6 and 11. J Gen Virol 1990; 71: 165–71.

    Article  PubMed  CAS  Google Scholar 

  57. Nishikawa T, Yamashita T, Yamada T et al. Tumorigenic transformation of primary rat embryonal fibroblasts by human papillomavirus type 8 E7 gene in collaboration with the activated H-ras gene. Jpn J Cancer Res 1991; 82: 1340–3.

    Article  PubMed  CAS  Google Scholar 

  58. Bouvard V, Matlashewski G, Gu ZM et al. The human papillomavirus type 16 E5 gene cooperates with the E7 gene to stimulate proliferation of primary cells and increases viral gene expression. Virology 1994; 203: 73–80.

    Article  PubMed  CAS  Google Scholar 

  59. Valle GF, Banks L. The human papillomavirus (HPV)-6 and HPV16 E5 proteins cooperate with HPV-16 E7 in the transformation of primary rodent cells. J Gen Virol 1995; 76: 1239–45.

    Article  PubMed  Google Scholar 

  60. Kaur P, McDougall JK. Characterization of primary human keratinocytes transformed by human papillomavirus type 18. J Virol 1988; 62: 1917–24.

    PubMed  CAS  Google Scholar 

  61. Hawley NP, Vousden KH, Hubbert NL et al. HPV16 E6 and E7 proteins cooperate to immortalize human foreskin keratinocytes. Embo J 1989; 8: 3905–10.

    Google Scholar 

  62. Munger K, Phelps WC, Bubb V et al. The E6 and E7 genes of the human papillomavirus type 16 together are necessary and sufficient for transformation of primary human keratinocytes. J Virol 1989; 63: 4417–21.

    PubMed  CAS  Google Scholar 

  63. Hudson JB, Bedell M A, McCance D J et al. Immortalization and altered differentiation of human keratinocytes in vitro by the E6 and E7 open reading frames of human papillomavirus type 18. J Virol 1990; 64: 519–526.

    PubMed  CAS  Google Scholar 

  64. Halbert CL, Demers GW, Galloway DA. The E7 gene of human papillomavirus type 16 is sufficient for immortalization of human epithelial cells. J Virol 1991; 65: 473–8.

    PubMed  CAS  Google Scholar 

  65. Barbosa MS, Schlegel R. The E6 and E7 genes of HPV-18 are sufficient for inducing two-stage in vitro transformation of human keratinocytes. Oncogene 1989; 4: 1529–32.

    PubMed  CAS  Google Scholar 

  66. von Knebel Doeberitz M, Rittmüller C, Aengenyndt F et al. Reversible repression of papillomavirus oncogene expression in cervical carcinoma cells: consequences for the phenotype and E6-p53 and E7pRB interactions. J Virol 1994; 68: 2811–2821.

    Google Scholar 

  67. Perez RN, Halbert CL, Smith PP et al. Immortalization of primary human smooth muscle cells. Proc Natl Acad Sci USA 1992; 89: 1224–8.

    Article  Google Scholar 

  68. Conroy SC, Hart CE, Perez RN et al. Characterization of human aortic smooth muscle cells expressing HPV16 E6 and E7 open reading frames. Am J Pathol 1995; 147: 753–62.

    PubMed  CAS  Google Scholar 

  69. Wazer DE, Liu XL, Chu Q et al. Immortalization of distinct human mammary epithelial cell types by human papillomavirus 16 E6 or E7. Proc Natl Acad Sci USA 1995; 92: 3687–91.

    Article  PubMed  CAS  Google Scholar 

  70. Tsao SW, Mok SC, Fey EG et al. Characterization of human ovarian surface epithelial cells immortalized by human papilloma viral oncogenes (HPV-E6E7 ORFs). Exp Cell Res 1995; 218: 499–507.

    Article  PubMed  CAS  Google Scholar 

  71. Foster SA, Galloway DA. Human papillomavirus type 16 E7 alleviates a proliferation block in early passage human mammary epithelial cells. Oncogene 1996; 12: 1773–9.

    PubMed  CAS  Google Scholar 

  72. Halbert CL, Demers GW, Galloway DA. The E6 and E7 genes of human papillomavirus type 6 have weak immortalizing activity in human epithelial cells. J Virol 1992; 66: 2125–34.

    PubMed  CAS  Google Scholar 

  73. Matsushime H, Roussel MF, Ashmun RA et al. Colony-stimulating factor 1 regulates novel cyclins during the G1 phase of the cell cycle. Cell 1991; 65: 701–713.

    Article  PubMed  CAS  Google Scholar 

  74. Won K-A, Xiong Y, Beach D et al. Growth-regulated expression of D-type cyclin genes in human diploid fibroblasts. Proc Natl Acad Sci USA 1992; 89: 9910–9914.

    Article  PubMed  CAS  Google Scholar 

  75. Johnson DG, Ohtani K, Nevins JR. Autoregulatory control of E2F1 expression in response to positive and negative regulators of cell cycle progression. Genes and Dev 1994; 8: 1514–1525.

    Article  PubMed  CAS  Google Scholar 

  76. Schulze A, Zerfaß K, Spitkovsky D et al. Activation of the E2F transcription factor by cyclin D1 is blocked by p16INK4, the product of the putative tumor suppressor gene MTS1. Oncogene 1994; 9: 3475–3482.

    PubMed  CAS  Google Scholar 

  77. Botz J, Zerfass-Thome K, Spitkovsky D et al. Cell cycle regulation of the murine cyclin E gene depends on an E2F binding site in the promoter. Mol Cell Biol 1996; 16: 3401–3409.

    CAS  Google Scholar 

  78. Ohtani K, Degregori J, Nevins JR. Regulation of the cyclin E gene by transcription factor E2F1. Proc Natl Acad Sci USA 1995; 92: 12146–12150.

    Article  CAS  Google Scholar 

  79. Schulze A, Zerfaß K, Spitkovsky D et al. Cell cycle regulation of cyclin A gene transcription is mediated by a variant E2F binding site. Proc Natl Acad Sci USA 1995; 92: 11264–11268.

    Article  PubMed  CAS  Google Scholar 

  80. Sherr CJ. Cancer cell cycles. Science 1996; 274: 1672–1677.

    Article  PubMed  CAS  Google Scholar 

  81. La Thangue NB. Drtfl/E2F-An expanding family of heterodimeric transcription factors implicated in cell-cycle control. Trends Biochem Sci 1994; 19: 108–114.

    Article  PubMed  Google Scholar 

  82. Lathangue NB. E2F and the molecular mechanisms of early cell-cycle control. Biochemical Society Transactions 1996; 24: 54–59.

    CAS  Google Scholar 

  83. Beijersbergen RL, Bernards R. Cell cycle regulation by the retino-blastoma family of growth inhibitory proteins. Biochimica et Biophysica Acta-Reviews on Cancer 1996; 1287: 103–120.

    Article  Google Scholar 

  84. Hunter T, Pines J. Cyclins and cancer 2. Cyclin D and CDK inhibitors come of age. Cell 1994; 79: 573–582.

    Article  PubMed  CAS  Google Scholar 

  85. El-Deiry WS, Tokino T, Velculescu VE et al. WAF1, a potential mediator of p53 tumor suppression. Cell 1993; 75: 817–825.

    Article  PubMed  CAS  Google Scholar 

  86. Banks L, Barnett SC, Crook T. HPV-16 E7 functions at the G1 to S phase transition in the cell cycle. Oncogene 1990; 5: 833–837.

    PubMed  CAS  Google Scholar 

  87. White AE, Livanos EM, Tlsty TD. Differential disruption of genomic integrity and cell cycle regulation in normal human fibroblasts by the HPV oncoproteins. Genes and Dev 1994; 8: 666–677.

    Article  PubMed  CAS  Google Scholar 

  88. Zerfaß K, Levy L, Cremonesi C et al. Cell cycle dependent disruption of E2F/p107 complexes by human papillomavirus type 16 E7. J Gen Virol 1995; 76: 1815–1820.

    Article  PubMed  Google Scholar 

  89. Hickman ES, Picksley SM, Vousden KH. Cells expressing HPV16 E7 continue cell cycle progression following DNA damage induced p53 activation. Oncogene 1994; 9: 2177–2181.

    PubMed  CAS  Google Scholar 

  90. Slebos RJC, Lee MH, Plunkett BS et al. p53-dependent G(1) arrest involves pRB-related proteins and is disrupted by the human papillomavirus 16 E7 oncoprotein. Proc Natl Acad Sci USA 1994; 91: 5320–5324.

    Article  PubMed  CAS  Google Scholar 

  91. Demers GW, Foster SA, Halbert CL et al. Growth arrest by induction of p53 in DNA damaged keratinocytes is bypassed by human papillomavirus 16 E7. Proc Natl Acad Sci USA 1994; 91: 4382–4386.

    Article  PubMed  CAS  Google Scholar 

  92. Vousden KH, Vojtisek B, Fisher C et al. HPV16 E7 or adenovirus E1A can overcome the growth arrest of cells immortalized with a temperature-sensitive p53. Oncogene 1993; 8: 1697–1702.

    PubMed  CAS  Google Scholar 

  93. Polyak K, Lee MH, Erdjumentbromage H et al. Cloning of p27(Kipl), a cyclin-dependent kinase inhibitor and a potential mediator of extracellular antimitogenic signals. Cell 1994; 78: 59–66.

    Article  PubMed  CAS  Google Scholar 

  94. Firpo EJ, Koff A, Solomon MJ et al. Inactivation of a Cdk2 inhibitor during interleukin 2-induced proliferation of human T lymphocytes. Mol and Cell Biol 1994; 14: 4889–4901.

    CAS  Google Scholar 

  95. Zerfass-Thome K, Zwerschke W, Mannhardt B et al. Inactivation of the cdk inhibitor p27KIP1 by the human papillomavirus type 16 E7 oncoprotein. Oncogene 1996; 13: 2323–2330.

    PubMed  CAS  Google Scholar 

  96. Pan H, Griep AE. Altered cell cycle regulation in the lens of HPV-16 E6 or E7 transgenic mice: implications for tumor suppressor gene function in development. Genes Dev 1994; 8: 1285–99.

    Article  PubMed  CAS  Google Scholar 

  97. Butz K, Shahabeddin L, Geisen C et al. Functional p53 protein in human papillomavirus-positive cancer cells. Oncogene 1995; 10: 927–936.

    PubMed  CAS  Google Scholar 

  98. Peacock JW, Chung S, Bristow RG et al. The p53-mediated G1 checkpoint is retained in tumorigenic rat embryo fibroblast clones transformed by the human papillomavirus type 16 E7 gene and EJ-ras. Mol Cell Biol 1995; 15: 1446–54.

    PubMed  CAS  Google Scholar 

  99. Spitkovsky D, Aengeneyndt F, Braspenning J et al. p53-independent growth regulation of cervical cancer cells by the papillomavirus E6 oncogene. Oncogene 1996; 13: 1027–1035.

    PubMed  CAS  Google Scholar 

  100. Boyer SN, Wazer DE, Band V. E7 protein of human papilloma virus-16 induces degradation of retinoblastoma protein through the ubiquitin-proteosome pathway. Cancer Res 1996; 56: 4620–4624.

    PubMed  CAS  Google Scholar 

  101. Stirdivant SM, Ahern JD, Oliff A et al. Retinoblastoma protein binding properties are dependent on 4 cysteine residues in the protein binding pocket. J Biol Chem 1992; 267: 14846–51.

    PubMed  CAS  Google Scholar 

  102. Wu EW, Clemens KE, Heck DV et al. The human papillomavirus E7 oncoprotein and the cellular transcription factor E2F bind to separate sites on the retinoblastoma tumor suppressor protein. J Virol 1993; 67: 2402–2407.

    PubMed  CAS  Google Scholar 

  103. Dyson N, Guida P, Munger K et al. Homologous sequences in adenovirus E1A and human papillomavirus E7 proteins mediate interactions with the same set of cellular proteins. J Virol 1992; 66: 6893–6902.

    PubMed  CAS  Google Scholar 

  104. Pagano M, Durst M, Joswig S et al. Binding of the human E2F transcription factor to the retinoblastoma protein but not to cyclin A is abolished in HPV-16-immortalized cells. Oncogene 1992; 7: 1681–1686.

    PubMed  CAS  Google Scholar 

  105. Chellappan S, Kraus V, Kroger B et al. Adenovirus E1A, simian virus 40 tumor antigen, and human papillomavirus E7 protein share the capacity to disrupt the interaction between transcription factor E2F and the retinoblastoma gene product. Proc Natl Acad Sci USA 1992; 89: 4549–4553.

    Article  PubMed  CAS  Google Scholar 

  106. Arroyo M, Bagchi S, Raychaudhuri P. Association of the human papillomavirus type-16 E7 protein with the S-phase-specific E2Fcyclin-A complex. Mol and Cell Biol 1993; 13: 6537–6546.

    CAS  Google Scholar 

  107. Phelps WC, Bagchi S, Barnes JA et al. Analysis of trans activation by human papillomavirus type 16 E7 and adenovirus 12S E1A suggests a common mechanism. J Virol 1991; 65: 6922–6930.

    PubMed  CAS  Google Scholar 

  108. Kovesdi I, Reichel R, Nevins JR. Identification of a cellular transcription factor involved in E1A trans-activation. Cell 1986; 45: 219–228.

    Article  PubMed  CAS  Google Scholar 

  109. Lam EWF, Morris JDH, Davies R et al. HPV16 E7 oncoprotein deregulates B-Myb expression-correlation with targeting of P107/E2F complexes. EMBO J 1994; 13: 871–878.

    PubMed  CAS  Google Scholar 

  110. Melillo RM, Helin K, Lowy DR et al. Positive and negative regulation of cell proliferation by E2F-1: Influence of protein level and human papillomavirus oncoproteins. Mol and Cell Biol 1994; 14: 8241–8249.

    CAS  Google Scholar 

  111. Lukas J, Müller H, Bartkova J et al. DNA tumor viruses oncoproteins and retinoblastoma gene mutations share the ability to relieve the cell’s requirement for cyclin D1 function in G1. J Cell Biol 1994; 125: 625–638.

    Article  PubMed  CAS  Google Scholar 

  112. Nichols GE, Williams ME, Gaffey MJ et al. Cyclin D1 gene expression in human cervical neoplasia. Modern Pathology 1996; 9: 418–425.

    PubMed  CAS  Google Scholar 

  113. Cavanaugh AH, Hempel WM, Taylor LJ et al. Activity of RNA polymerase I transcription factor UBF blocked by Rb gene product. Nature 1995; 374: 177–180.

    Article  PubMed  CAS  Google Scholar 

  114. White RJ, Trouche D, Martin K et al. Repression of RNA polymerase III transcription by the retinoblastoma protein [see comments]. Nature 1996; 382: 88–90.

    Article  PubMed  CAS  Google Scholar 

  115. Antinore MJ, Birrer MJ, Patel D et al. The human papillomavirus type 16 E7 gene product interacts with and trans-activates the AP1 family of transcription factors. EMBO J 1996; 15: 1950–1960.

    PubMed  CAS  Google Scholar 

  116. Wong HK, Ziff EB. The human papillomavirus type 16 E7 protein complements adenovirus type 5 E1A amino-terminus-dependent transactivation of adenovirus type 5 early genes and increases ATF and Oct-1 DNA binding activity. J Virol 1996; 70: 332–340.

    PubMed  CAS  Google Scholar 

  117. Mazzarelli JM, Atkins GB, Geisberg JV et al. The viral oncoproteins Ad5 E1A, HPV16 E7 and SV40 TAg bind a common region of the TBP-associated factor-110. Oncogene 1995; 11: 1859–1864.

    PubMed  CAS  Google Scholar 

  118. Münger K, Yee C, Phelps W et al. Biochemical and biological differences between the E7 oncoproteins of the high-and low-risk human papillomavirus types are determined by amino-terminal sequences. J Virol 1991; 65: 3943–3948.

    PubMed  Google Scholar 

  119. Ibaraki T, Satake M, Kurai N et al. Transacting activities of the E7 genes of several types of human papillomavirus. Virus Genes 1993; 7: 187–196.

    Article  PubMed  CAS  Google Scholar 

  120. Zajchowski DA, Boeuf H, Kedinger C. Ela inducibility of the adenoviral early E2a promoter is determined by specific combinations of sequence elements. Gene 1987; 58: 243–256.

    Article  PubMed  CAS  Google Scholar 

  121. Rawls JA, Pusztai R, Green M. Chemical synthesis of human papillomavirus type 16 E7 oncoprotein: autonomous protein domains for induction of cellular DNA synthesis and for trans activation. J Virol 1990; 64: 6121–9.

    PubMed  CAS  Google Scholar 

  122. Morosov A, Phelps WC, Raychaudhuri P. Activation of the c-fos gene by the HPV16 oncoproteins depends upon the cAMP-response element at -60. J Biol Chem 1994; 269: 18434–18440.

    PubMed  CAS  Google Scholar 

  123. Morozov A, Subjeck J, Raychaudhuri P. HPV16 E7 oncoprotein induces expression of a 110 kDa heat shock protein. FEBS Letters 1995; 371: 214–218.

    Article  PubMed  CAS  Google Scholar 

  124. Nishida M, Miyamoto S, Kato H et al. Transcriptional repression of smooth-muscle a-actin gene associated with human papillomavirus type 16 E7 expression. Molecular Carcinogenesis 1995; 13: 157–165.

    Article  PubMed  CAS  Google Scholar 

  125. Tommasino M, Adamczewski JP, Carlotti F et al. HPV16 E7 protein associates with the protein kinase p33CDK2 and cyclin A. Oncogene 1993; 8: 195–202.

    PubMed  CAS  Google Scholar 

  126. Mcintyre MC, Ruesch MN, Laimins LA. Human papillomavirus E7 oncoproteins bind a single form of cyclin E in a complex with cdk2 and p107. Virology 1996; 215: 73–82.

    CAS  Google Scholar 

  127. Shirodkar S, Ewen M, DeCaprio JA et al. The transcription factor E2F interacts with the retinoblastoma product and a p107-cyclin A complex in a cell cycle-regulated manner. Cell 1992; 68: 157–166.

    Article  PubMed  CAS  Google Scholar 

  128. Xiong Y, Kuppuswamy D, Li Y et al. Alteration of cell cycle kinase complexes in human papillomavirus E6- and E7-expressing fibroblasts precedes neoplastic transformation. J Virol 1996; 70: 999–1008.

    PubMed  CAS  Google Scholar 

  129. Khleif SN, DeGregori J, Yee CL et al. Inhibition of cyclin D-CDK4/ CDK6 activity is associated with an E2F-mediated induction of cyclin kinase inhibitor activity. Proc Natl Acad Sci USA 1996; 93: 4350–4.

    Article  PubMed  CAS  Google Scholar 

  130. Jewers R, Hildebrandt P, Ludlow J et al. Regions of HPV 16 E7 oncoprotein required for immortalization of human keratinocytes. J Virol 1992; 66: 1329–1335.

    PubMed  CAS  Google Scholar 

  131. Ohtsubo M, Theodoras AM, Schumacher J et al. Human cyclin E, a nuclear protein essential for the G(1)-to-S phase transition. Mol and Cell Biol 1995; 15: 2612–2624.

    CAS  Google Scholar 

  132. Howes KA, Ransom N, Papermaster DS et al. Apoptosis or retino-blastoma: alternative fates of photoreceptors expressing the HPV-16 E7 gene in the presence or absence of p53. Genes Dev 1994; 8: 1300–10.

    Article  PubMed  CAS  Google Scholar 

  133. Pan HC, Griep AE. Temporally distinct patterns of p53-dependent and p53-independent apoptosis during mouse lens development. Genes and Dev 1995; 9: 2157–2169.

    Article  PubMed  CAS  Google Scholar 

  134. Puthenveettil JA, Frederickson SM, Reznikoff CA. Apoptosis in human papillomavirus 16 E7, but not E6-immortalized human urorpithelial cells. Oncogene 1996; 13: 1123–1131.

    PubMed  CAS  Google Scholar 

  135. Isacson C, Kessis TD, Hedrick L et al. Both cell proliferation and apoptosis increase with lesion grade in cervical neoplasia but do not correlate with human papillomavirus type. Cancer Res 1996; 56: 669–74.

    PubMed  CAS  Google Scholar 

  136. Lees E. Cyclin dependent kinase regulation. Curr Opin Cell Biol 1995; 7: 773–780.

    Article  PubMed  CAS  Google Scholar 

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Authors
  1. Massimo Tommasino
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  2. Pidder Jansen-Dürr
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© 1997 Springer-Verlag Berlin Heidelberg

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Tommasino, M., Jansen-Dürr, P. (1997). E7 Protein. In: Papillomaviruses in Human Cancer. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-6127-6_4

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  • DOI: https://doi.org/10.1007/978-1-4757-6127-6_4

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