HPV E6 oncoprotein as a potential therapeutic target in HPV related cancers

Expert Opinion on Therapeutic Targets

Volumn 17, Issue 11, 2013, Pages 1357-1368

  Manzo Merino, Joaquin ^b   Thomas, Miranda ^a   Fuentes Gonzalez, Alma M ^b   Lizano, Marcela ^b   Banks, Lawrence ^a  

^a INTERNATIONAL CENTRE FOR GENETIC ENGINEERING AND BIOTECHNOLOGY   (Italy)

^b UNIVERSIDAD NACIONAL AUTÓNOMA DE MÉXICO   (Mexico)

Author keywords

Cancer; E6; HPV; Therapy

Indexed keywords

HUMAN PAPILLOMAVIRUS E6 ONCOPROTEIN; PROTEASOME INHIBITOR; PROTEIN E6; UNCLASSIFIED DRUG; WART VIRUS VACCINE;

BIOLOGICAL ACTIVITY; DISEASE ASSOCIATION; EPITHELIUM HYPERPLASIA; HUMAN; HUMAN PAPILLOMAVIRUS TYPE 16; HUMAN PAPILLOMAVIRUS TYPE 18; IMMUNIZATION; MALIGNANT TRANSFORMATION; MELANOMA SKIN CANCER; NEOPLASM; NONHUMAN; PAPILLOMAVIRUS INFECTION; PDZ DOMAIN; REVIEW; UTERINE CERVIX CANCER; WART VIRUS;

ALPHAPAPILLOMAVIRUS; AMINO ACID SEQUENCE; HUMANS; NEOPLASMS; ONCOGENE PROTEINS, VIRAL; SEQUENCE HOMOLOGY, AMINO ACID;

EID: 84886887522     PISSN: 14728222     EISSN: 17447631     Source Type: Journal    
DOI: 10.1517/14728222.2013.832204     Document Type: Review

References (114)

1. de Villiers EM, Fauquet C, Broker TR, et al. Classification of papillomaviruses. Virology 2004;324:17-27
2. Bouvard V, Baan R, Straif K, et al. WHO International Agency for Research on Cancer Monograph Working Group. Lancet Oncol 2009;10:321-2
3. Doorbar J. The papillomavirus life cycle. J Clin Virol 2005;32(Suppl 1):S7-15
4. Joyce JG, Tung JS, Przysiecki CT, et al. The L1 major capsid protein of human papillomavirus type 11 recombinant virus-like particles interacts with heparin and cell-surface glycosaminoglycans on human keratinocytes. J Biol Chem 1999;274:5810-22
5. Giroglou T, Florin L, Schäfer F, et al. Human papillomavirus infection requires cell surface heparan sulfate. J Virol 2001;75:1565-70
6. Day PM, Lowy DR, Schiller JT. Papillomaviruses infect cells via a clathrin-dependent pathway. Virology 2003;307:1-11
7. Schelhaas M, Shah B, Holzer M, et al. Entry of human papillomavirus type 16 by actin-dependent, clathrin-and lipid raft-independent endocytosis. PLoS Pathog 2012;8:e1002657
8. Kämper N, Day PM, Nowak T, et al. A membrane-destabilizing peptide in capsid protein L2 is required for egress of papillomavirus genomes from endosomes. J Virol 2006;80:759-68
9. Pyeon D, Pearce SM, Lank SM, et al. Establishment of human papillomavirus infection requires cell cycle progression. PLoS Pathog 2009;5:e1000318
10. Stenlund A. Initiation of DNA replication: lessons from viral initiator proteins. Nat Rev Mol Cell Biol 2003;4:777-85
11. Oliveira JG, Colf LA, McBride AA. Variations in the association of papillomavirus E2 proteins with mitotic chromosomes. Proc Natl Acad Sci USA 2006;103:1047-52
12. McLaughlin-Drubin ME, Münger K. The human papillomavirus E7 oncoprotein. Virology 2009;384:335-44
13. Fan X, Chen JJ. Regulation of cell cycle progression and apoptosis by the papillomavirus E6 oncogene. Crit Rev Eukaryot Gene Expr 2004;14:183-202
14. Nakahara T, Peh WL, Doorbar J, et al. Human papillomavirus type 16 E1 E4 contributes to multiple facets of the papillomavirus life cycle. J Virol 2005;79:13150-65
15. Wilson R, Fehrmann F, Laimins LA. Role of the E1-E4 protein in the differentiation-dependent life cycle of human papillomavirus type 31. J Virol 2005;79:6732-40
16. Conway MJ, Meyers C. Replication and assembly of Human Papillomaviruses. J Dent Res 2009;88:307-17
17. Doorbar J, Quint W, Banks L, et al. The biology and life-cycle of human papillomaviruses. Vaccine 2012;30(Suppl 5):F55-70
18. Androphy EJ, Hubbert NL, Schiller JT, et al. Identification of the HPV-16 E6 protein from transformed mouse cells and human cervical carcinoma cell lines. EMBO J 1987;6:989-92
19. Banks L, Spence P, Androphy E, et al. Identification of human papillomavirus type 18 E6 polypeptide in cells derived from human cervical carcinomas. J Gen Virol 1987;68:1351-9
20. Smotkin D, Wettstein FO. Transcription of human papillomavirus type 16 early genes in a cervical cancer and a cancer-derived cell line and identification of the E7 protein. Proc Natl Acad Sci USA 1986;83:4680-4
21. Jabbar SF, Park S, Schweizer J, et al. Cervical cancers require the continuous expression of the human papillomavirus type 16 E7 oncoprotein even in the presence of the viral E6 oncoprotein. Cancer Res 2012;72:4008-16
22. Magaldi TG, Almstead LL, Bellone S, et al. Primary human cervical carcinoma cells require human papillomavirus E6 and E7 expression for ongoing proliferation. Virology 2012;422:114-24
23. Schwarz E, Freese UK, Gissmann L, et al. Structure and transcription of human papillomavirus sequences in cervical carcinoma cells. Nature 1985;314:111-14
24. Yee C, Krishnan-Hewlett I, Baker CC, et al. Presence and expression of human papillomavirus sequences in human cervical carcinoma cell lines. Am J Pathol 1985;119:361-6
25. Jeon S, Allen-Hoffmann BL, Lambert PF. Integration of human papillomavirus type 16 into the human genome correlates with a selective growth advantage of cells. J Virol 1995;69:2989-97
26. Jeon S, Lambert PF. Integration of human papillomavirus type 16 DNA into the human genome leads to increased stability of E6 and E7 mRNAs: implications for cervical carcinogenesis. Proc Natl Acad Sci USA 1995;92:1654-8
27. von Knebel Doeberitz M, Rittmüller C, zur Hausen H, et al. Inhibition of tumorigenicity of cervical cancer cells in nude mice by HPV E6-E7 anti-sense RNA. Int J Cancer 1992;51:831-4
28. Alvarez-Salas LM, Arpawong TE, DiPaolo JA. Growth inhibition of cervical tumor cells by antisense oligodeoxynucleotides directed to the human papillomavirus type 16 E6 gene. Antisense Nucleic Acid Drug Dev 1999;9:441-50
29. Butz K, Denk C, Ullmann A, et al. Induction of apoptosis in human papillomavirus positive cancer cells by peptide aptamers targeting the viral E6 oncoportein. Proc Natl Acad Sci USA 2000;97:6693-7
30. Nauenburg S, Zwerschke W, Jansen-Durr P. Induction of apoptosis in cervical carcinoma cells by peptide aptamers that bind to the HPV-16 E7 oncoprotein. FASEB J 2001;15:592-4
31. Butz K, Ristriani T, Hengstermann A, et al. siRNA targeting of the viral E6 oncogene efficiently kills human papillomavirus-positive cancer cells. Oncogene 2003;22:5938-45
32. Yoshinouchi M, Yamada T, Kizaki M, et al. In vitro and in vivo growth suppression of human papillomavirus 16-positive cervical cancer cells by E6 siRNA. Mol Ther 2003;8:762-8
33. Hall AH, Alexander KA. RNA interference of human papillomavirus type 18 E6 and E7 induces senescence in HeLa cells. J Virol 2003;77:6066-9
34. Nicol C, Cesur O, Forrest S, et al. An RNA aptamer provides a novel approach for the induction of apoptosis by targeting the HPV16 E7 oncoprotein. PLoS One 2013;8:e64781
35. Griffin H, Elston R, Jackson D, et al. Inhibition of papillomavirus protein function in cervical cancer cells by intrabody targeting. J Mol Biol 2006;355:360-78
36. Lin Z, Bazzaro M, Wang MC, et al. Combination of proteasome and HDAC inhibitors for uterine cervical cancer treatment. Clin Cancer Res 2009;15:570-7
37. Stern PL, van der Burg SH, Hampson IN, et al. Therapy of human papillomavirus-related disease. Vaccine 2012;30(Suppl F5):F71-82
38. Monie A, Hung CF, Roden R, et al. Cervarix: a vaccine for the prevention of HPV 16, 18-associated cervical cancer. Biologics 2008;2:97-105
39. Kjaer SK, Sigurdsson K, Iversen OE, et al. A pooled analysis of continued prophylactic efficacy of quadrivalent human papillomavirus (types 6/11/16/18) vaccine against high-grade cervical and external genital lesions. Cancer Prev Res 2009;2:868-78
40. Harper DM. Currently approved prophylactic HPV vaccines. Expert Rev Vaccines 2009;8:1663-79
41. Munoz N, Kjaer SK, Sigurdsson K, et al. Impact of Human papillomavirus (HPV)-6/11/16/18 vaccine on all HPV-associated genital diseases in young women. J Natl Cancer Inst 2010;102:325-39
42. Fisher H, Trotter CL, Audrey S, et al. Inequalities in the uptake of Human Papillomavirus Vaccination: a systematic review and meta-analysis. Int J Epidemiol 2013; In press
43. Moody CA, Laimins LA. Human papillomavirus oncoproteins: pathways to transformation. Nat Rev Cancer 2010; 10: 550-60
44. Vande Pol SB, Klingelhutz AJ. Papillomavirus E6 oncoproteins. Virology 2013; In press
45. Thomas M, Matlashewski G, Pim D, et al. Induction of apoptosis by p53 is independent of its oligomeric state and can be abolished by HPV-18 E6 through ubiquitin mediated degradation. Oncogene 1996;13:265-73
46. Thomas M, Banks L. Inhibition of Bak-induced apoptosis by HPV-18 E6. Oncogene 1998;17:2943-54
47. Hawley-Nelson P, Vousden KH, Hubbert NL, et al. HPV16 E6 and E7 proteins cooperate to immortalize human foreskin keratinocytes. EMBO J 1989;8:3905-10
48. 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
49. Duensing S, Munger K. The human papillomavirus type 16 E6 and E7 oncoproteins independently induce numerical and structural chromosome instability. Cancer Res 2002;62:7075-82
50. Melsheimer P, Vinokurova S, Wentzensen N, et al. DNA aneuploidy and integration of human papillomavirus type 16 E6/E7 oncogenes in intraepithelial neoplasia and invasive squamous cell carcinoma of the cervix uteri. Clin Cancer Res 2004;10:3059-63
51. Klingelhutz AJ, Foster SA, McDougall JK. Telomerase activation by the E6 gene product of human papillomavirus type 16. Nature 1996;380:79-82
52. Watson RA, Thomas M, Banks L, et al. Activity of the human papillomavirus E6 PDZ-binding motif correlates with an enhanced morphological transformation of immortalised human keratinocytes. J Cell Sci 2003;116:4925-34
53. D'Costa ZJ, Jolly C, Androphy EJ, et al. Transcriptional repression of E-cadherin by human papillomavirus type 16 E6. PLoS One 2012;7:e48954
54. Ronco LV, Karpova AY, Vidal M, et al. Human papillomavirus 16 E6 oncoprotein binds to interferon regulatory factor-3 and inhibits its transcriptional activity. Genes Dev 1998;12:2061-72
55. Hong S, Mehta KP, Laimins LA. Suppression of STAT-1 expression by human papillomaviruses is necessary for differentiation-dependent genome amplification and plasmid maintenance. J Virol 2011;85:9486-94
56. Lambert PF, Pan H, Pitot HC, et al. Epidermal cancer associated with expression of human papillomavirus type 16 E6 and E7 oncogenes in the skin of transgenic mice. Proc Natl Acad Sci USA 1993;90:5583-7
57. Shai A, Brake T, Somoza C, et al. The human papillomavirus E6 oncogene dysregulates the cell cycle and contributes to cervical carcinogenesis through two independent activities. Cancer Res 2007;67:1626-35
58. Jabbar S, Strat K, Shin et al. Human papillomavirus type 16 E6 and E7 oncoproteins act synergistically to cause head and neck cancer in mice. Virology 2010;407:60-70
59. Shai A, Pitot HC, Lambert PF. E6-associated protein is required for human papillomavirus type 16 E6 to cause cervical cancer in mice. Cancer Res 2010;70:5064-73
60. Song S, Liem A, Miller JA, et al. Human papillomavirus types 16 E6 and E7 contribute differently to carcinogenesis. Virology 2000;267:141-50
61. Chen JJ, Reid CE, Band V, et al. Interaction of papillomavirus E6 oncoproteins with a putative calcium-binding protein. Science 1995;269:529-31
62. Vande Pol SB, Brown MC, Turner CE. Association of Bovine Papillomavirus Type 1 E6 oncoprotein with the focal adhesion protein paxillin through a conserved protein interaction motif. Oncogene 1998;16:43-52
63. Elston RC, Napthine S, Doorbar J. The identification of a conserved binding motif within human papillomavirus type 16 E6 binding peptides, E6AP and E6BP. J Gen Virol 1998;79:371-4
64. Scheffner M, Werness BA, Huibregtse JM, et al. The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53. Cell 1990;63:1129-36
65. Huibregtse JM, Scheffner M, Howley PM. Cloning and expression of the cDNA for E6-AP, a protein that mediates the interaction of the human papillomavirus E6 oncoprotein with p53. Mol Cell Biol 1993;13:775-84
66. Scheffner M, Huibregtse JM, Vierstra RD, et al. The HPV-16 E6 and E6-AP complex functions as a ubiquitin-protein ligase in the ubiquitination of p53. Cell 1993;75:495-505
67. Scheffner M, Munger K, Byrne JC, et al. The state of p53 and retinoblastoma genes in human cervical carcinoma cell lines. Proc Natl Acad Sci USA 1991;88:5523-7
68. Denk C, Butz K, Schneider A, et al. p53 mutations are rare events in recurrent cervical cancer. J Mol Med 2001;79:283-8
69. Nawaz Z, Lonard DM, Smith CL, et al. The Angelman śindrome- associated protein, E6-AP, is a coactivator for the nuclear hormone receptor superfamily. Mol Cell Biol 1999;19:1182-9
70. Kishino T, Lalande M, Wagstaff J. UBE3A/E6-AP mutations cause Angelman syndrome. Nat Genet 1997;15:70-3
71. Matsuura T, Sutcliffe JS, Fang P, et al. De novo truncating mutations in E6-AP ubiquitin-protein ligase gene (UBE3A) in Angelman syndrome. Nat Genet 1997;15:74-7
72. Tomaić V, Pim D, Banks L. The stability of the human papillomavirus E6 oncoprotein is E6AP dependent. Virology 2009;393:7-10
73. Zanier K, Charbonnier S, Sidi AO, et al. Structural basis for hijacking of cellular LxxLL motifs by papillomavirus E6 oncoproteins. Science 2013;339:694-8
74. Baleja JD, Cherry JJ, Liu Z, et al. Identification of inhibitors to papillomavirus type 16 E6 protein based on three-dimensional structures of interacting proteins. Antiviral Res 2006;72:49-59
75. Sterlinko Grm H, Weber M, Elston R, et al. Inhibition of E6-induced degradation of its cellular substrates by novel blocking peptides. J Mol Biol 2004;335:971-85
76. Kho EY, Wang HK, Banerjee NS, et al. HPV-18 E6 mutants reveal p53 modulation of viral DNA amplication in organotypic cultures. Proc Natl Acad Sci USA 2013;110:7542-9
77. Liu Y, Chen J, Gao Q, et al. Multiple functions of human papillomavirus type 16 E6 contribute to immortalization of mammary epithelial cells. J Virol 1999;73:7297-307
78. Sherman L, Itzhaki H, Jackman A, et al. Inhibition of serum-and calcium-induced terminal differentiation of human keratinocytes by HPV 16 E6: study of the association with p53 degradation, inhibiton of p53 transactivation, and binding to E6BP. Virology 2002;292:309-20
79. Shai A, Nguyen ML, Wagstaff J, et al. HPV16 E6 confers p53-dependent and p53-independent phenotypes in the epidermis of mice deficient for E6AP. Oncogene 2007;26:3321-8
80. Nguyen M, Song S, Liem A, et al. A mutant of human papillomavirus type 16 E6 deficient in binding alpha-helix partners displays reduced oncogenic potential in vivo. J Virol 2002;76:13039-48
81. Thomas MC, Chiang CM. E6 oncoprotein represses p53-dependent gene activation via inhibition of protein acetylation independently of inducing p53 degradation. Mol Cell 2005;17:251-64
82. Walts AE, Koeffler HP, Said JW. Localisation of p53 protein and human papillomavirus in anogenital squamous lesions: immunohistochemical and in situ hybridization studies in benign, dysplastic and malignant epithelia. Hum Pathol 1993;24:1238-42
83. Ter Harmsel B, van Nelkum A, Quint W, et al. P53 and human papiloma virus type 16 in cervical intraepithelial neoplasia and carcinoma. Int J Gynecol Pathol 1995;14:125-33
84. Akasofu M, Oda Y. Immunohistochemical detection of p53 in cervical epithelial lesions with or without infection of human papillomavirus types 16 and 18. Virchows Arch 1995;425:593-602
85. Kurvinen K, Syrjanen K. Syrjanen S. p53 and Bcl-2 proteins as prognostic markers in human papillomavirus-associated cervical lesions. J Clin Oncol 1996;14:2120-30
86. Doyle DA, Lee A, Lewis J, et al. Crystal structures of a complexed and peptide-free membrane protein-binding domain: molecular basis of peptide recognition by PDZ. Cell 1996;85:1067-76
87. Songyang Z, Fanning AS, Fu C, et al. Recognition of unique carboxyl-terminal motifs by distinct PDZ domains. Science 1997;275:73-7
88. Lee HJ, Zheng JJ. PDZ domains and their binding partners: structure, specificity, and modification. Cell Commun Signal 2010;8:8
89. Kiyono T, Hiraiwa A, Ito S, et al. Binding of high-risk human papillomavirus E6 oncoproteins to a human homologue of the Drosophila discs large tumour suppressor protein. Proc Natl Acad Sci USA 1997;94:11612-16
90. Lee SS, Weiss R, Javier R. Binding of human virus oncoproteins to hDlg/SAP97, a mammalian homologue of the Drosophila discs large tumour suppressor protein. Proc Natl Acad Sci USA 1997;94:6670-5
91. Thomas M, Narayan N, Pim D, et al. Human papillomaviruses, cervical cancer and cell polarity. Oncogene 2008;27:7018-30
92. Gardiol D, Kühne C, Glaunsinger B, et al. Oncogenic human papillomavirus E6 proteins target the discs large tumour suppressor for proteasome-mediated degradation. Oncogene 1999;18:5487-96
93. Nakagawa S, Huibregtse JM. Human scribble (Vartul) is targeted for ubiquitin-mediated degradation by the high-risk papillomavirus E6 proteins and the E6AP ubiquitin-protein ligase. Mol Cell Biol 2000;20:8244-53
94. Bilder D, Schober M, Perrimon N. Integrated activity of PDZ protein complexes regulates epithelial polarity. Nat Cell Biol 2003;5:53-8
95. Watson RA, Rollason TP, Reynolds GM, et al. Changes in expression of the human homologue of the Drosophila discs large tumour suppressor protein in high-grade premalignant cervical lesions. Carcinogenesis 2002;23:1791-6
96. Navarro C, Nola S, Audebert S, et al. Juntional recruitment of mammalian Scribble relies on E-cadherin engagement. Oncogene 2005;24:4330-9
97. Cavatorta AL, Fumero G, Chouhy D, et al. Differential expression of the human homologue of drosophila discs large oncosuppressor in histologic samples from human papillomavirus-associated lesions as a marker for progression to malignancy. Int J Cancer 2004;111:373-80
98. Gardiol D, Zacchi A, Petrera F, et al. Human discs large and scrib are localized at the same regions in colon mucosa and changes in their expression patterns are correlated with loss of tissue architecture during malignant progression. Int J Cancer 2006;119:1285-90
99. Banks L, Pim D, Thomas M. Human tumour viruses and the deregulation of cell polarity in cancer. Nat Rev Cancer 2012;12:877-86
100. Thomas M, Massimi P, Navarro C, et al. The hScrib/Dlg apico-basal control complex is differentially targeted by HPV-16 and HPV-18 E6 proteins. Oncogene 2005;24:6222-30
101. Zhang Y, Dasgupta J, Ma RZ, et al. Structures of a human papillomavirus (HPV) E6 polypeptide bound to MAGUK proteins: mechanisms of targeting tumor suppressors by a high-risk HPV oncoprotein. J Virol 2007;81:3618-26
102. Thomas M, Dasgupta J, Zhang Y, et al. Analysis of specificity determinants in the interactions of different HPV E6 proteins with their PDZ domain-containing substrates. Virology 2008;376:371-8
103. Liu Y, Henry GD, Hedge RS, et al. Solution structure of the hDlg/SAP97 PDZ2 domain and its mechanism of interaction with HPV-18 papillomavirus E6 protein. Biochemistry 2007;46:10864-74
104. Fournane S, Charbonnier S, Chapelle A, et al. Surface plasmon resonance analysis of the binding of high-risk mucosal HPV E6 oncoprotein to the PDZ1 domain of the tight junction protein MAGI-1. J Mol Recogn 2011;24:511-23
105. Charbonnier S, Nomine Y, Ramirez J, et al. The strucutural and dynamic response of MAGI-1 PDZ1 with noncanonical domain bounderies to the binding of human papillomavirus E6. J Mol Biol 2011;406:745-63
106. Boon SS, Banks L. High-risk human papillomavirus E6 oncoproteins interact with 14-3-3z in a PDZ binding motif-dependent manner. J Virol 2013;87:1586-95
107. Lee C, Laimins LA. Role of the PDZ domain-binding motif of the oncoprotein E6 in the pathogenesis of human papillomavirus type 31. J Virol 2004;78:12366-77
108. Nicolaides L, Davy C, Raj K, et al. Stabilization of HPV16 E6 protein by PDZ proteins, and potential implications for genome maintenance. Virology 2011;414:137-45
109. Delury CP, Marsh E, James CD, et al. The role of protein kinase A regulation of the E6 PDZ-binding domain during the differentiation-dependent life cycle of human papillomavirus type 18. In press
110. Spanos WC, Hoover A, Harris GF, et al. The PDZ binding motif of human papillomavirus type 16 E6 induces PTPN13 loss, which allows anchorage- independent growth and synergises with ras for invasive growth. J Virol 2008;82:2493-500
111. White EA, Kramer RE, Tan MJ, et al. Comprehensive analysis of host cellular interactions with human papillomavirus E6 proteins identifies new E6 binding partners and reflects viral diversity. J Virol 2012;86:13174-86
112. Brimer N, Lyons C, Wallberg AE, et al. Cutaneous papillomavirus E6 oncoproteins associate with MAML1 to repress transactivation and NOTCH signaling. Oncogene 2012;31:4639-46
113. IARC report. A review of human carcinogens. Part B: Biological agents/IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, Lyon, France; 2009
114. Parkin DM. The global health burden of infection-associated cancers in the year 2002. Int J Cancer 2006;118:3030-44