Advertisement

HPV Virology: Cellular Targets of HPV Oncogenes and Transformation

  • Eric A. SmithEmail author
  • Marie C. Matrka
  • Susanne I. Wells
Chapter
  • 799 Downloads

Abstract

A subtype of head and neck cancer (HNC) characterized by infection with human papillomavirus (HPV) is clinically and molecularly distinct from classical HNC. In general these tumors arise in younger patients and respond better to therapy, while also expressing wild-type tumor suppressor proteins. Owing to these observations, efforts are currently being made to understand HPV+ HNC biology to improve clinical treatment regimens and develop novel therapeutic agents. To best predict which treatment strategies and novel therapeutics will have the most impact in patient care, a working understanding of how the HPV arsenal of oncogenes manipulates and transforms cells is crucial. This chapter will highlight the most important and clinically interesting cellular targets of the HPV oncogenes; the mechanisms by which the viral oncogenes subvert cell cycle checkpoints, DNA repair, immune surveillance, and cell death to promote malignant transformation; and promising future therapeutic options to target the functions of HPV oncogenes.

Keywords

HPV E2 E5 E6 E7 Head and neck cancer DNA repair Mitosis Immune evasion Transformation 

Notes

Acknowledgments

This work was funded by two NIH awards: RO1 CA116316 and CA102357. Special thanks are given to Timothy Chlon for his critical input and discussion of the manuscript.

References

  1. Abbate EA, Voitenleitner C, Botchan MR (2006) Structure of the papillomavirus DNA-tethering complex E2:Brd4 and a peptide that ablates HPV chromosomal association. Mol Cell 24:877–889PubMedGoogle Scholar
  2. Adey A, Burton JN, Kitzman JO, Hiatt JB, Lewis AP, Martin BK et al (2013) The haplotype-resolved genome and epigenome of the aneuploid HeLa cancer cell line. Nature 500:207–211PubMedCentralPubMedGoogle Scholar
  3. Agrawal N, Frederick MJ, Pickering CR, Bettegowda C, Chang K, Li RJ et al (2011) Exome sequencing of head and neck squamous cell carcinoma reveals inactivating mutations in NOTCH1. Science 333:1154–1157PubMedCentralPubMedGoogle Scholar
  4. Akagi K, Li J, Broutian TR, Padilla-Nash H, Xiao W, Jiang B et al (2014) Genome-wide analysis of HPV integration in human cancers reveals recurrent, focal genomic instability. Genome Res 24:185–199PubMedCentralPubMedGoogle Scholar
  5. Alter BP, Giri N, Savage SA, Quint WG, de Koning MN, Schiffman M (2013) Squamous cell carcinomas in patients with Fanconi anemia and dyskeratosis congenita: a search for human papillomavirus. Int J Cancer 133:1513–1515PubMedCentralPubMedGoogle Scholar
  6. Andreassen PR, D’Andrea AD, Taniguchi T (2004) ATR couples FANCD2 monoubiquitination to the DNA-damage response. Genes Dev 18:1958–1963PubMedCentralPubMedGoogle Scholar
  7. Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Tan PF et al (2010) Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med 363:24–35PubMedCentralPubMedGoogle Scholar
  8. Antonsson A, Payne E, Hengst K, McMillan NA (2006) The human papillomavirus type 16 E7 protein binds human interferon regulatory factor-9 via a novel PEST domain required for transformation. J Interferon Cytokine Res 26:455–461PubMedGoogle Scholar
  9. Arbeit JM, Howley PM, Hanahan D (1996) Chronic estrogen-induced cervical and vaginal squamous carcinogenesis in human papillomavirus type 16 transgenic mice. Proc Natl Acad Sci U S A 93:2930–2935PubMedCentralPubMedGoogle Scholar
  10. Ashrafi GH, Haghshenas M, Marchetti B, Campo MS (2006) E5 protein of human papillomavirus 16 downregulates HLA class I and interacts with the heavy chain via its first hydrophobic domain. Int J Cancer 119:2105–2112PubMedGoogle Scholar
  11. Asumalahti K, Veal C, Laitinen T, Suomela S, Allen M, Elomaa O et al (2002) Coding haplotype analysis supports HCR as the putative susceptibility gene for psoriasis at the MHC PSORS1 locus. Hum Mol Genet 11:589–597PubMedGoogle Scholar
  12. Avvakumov N, Torchia J, Mymryk JS (2003) Interaction of the HPV E7 proteins with the pCAF acetyltransferase. Oncogene 22:3833–3841PubMedGoogle Scholar
  13. Baker CC, Phelps WC, Lindgren V, Braun MJ, Gonda MA, Howley PM (1987) Structural and transcriptional analysis of human papillomavirus type 16 sequences in cervical carcinoma cell lines. J Virol 61:962–971PubMedCentralPubMedGoogle Scholar
  14. Barbaresi S, Cortese MS, Quinn J, Ashrafi GH, Graham SV, Campo MS (2010) Effects of human papillomavirus type 16 E5 deletion mutants on epithelial morphology: functional characterization of each transmembrane domain. J Gen Virol 91:521–530PubMedGoogle Scholar
  15. Bernard BA, Bailly C, Lenoir MC, Darmon M, Thierry F, Yaniv M (1989) The human papillomavirus type 18 (HPV18) E2 gene product is a repressor of the HPV18 regulatory region in human keratinocytes. J Virol 63:4317–4324PubMedCentralPubMedGoogle Scholar
  16. Bernat A, Avvakumov N, Mymryk JS, Banks L (2003) Interaction between the HPV E7 oncoprotein and the transcriptional coactivator p300. Oncogene 22:7871–7881PubMedGoogle Scholar
  17. Boon SS, Banks L (2013) High-risk human papillomavirus E6 oncoproteins interact with 14-3-3zeta in a PDZ binding motif-dependent manner. J Virol 87:1586–1595PubMedCentralPubMedGoogle Scholar
  18. Boulenouar S, Weyn C, Van Noppen M, Moussa Ali M, Favre M, Delvenne PO et al (2010) Effects of HPV-16 E5, E6 and E7 proteins on survival, adhesion, migration and invasion of trophoblastic cells. Carcinogenesis 31:473–480PubMedGoogle Scholar
  19. Boyer SN, Wazer DE, Band V (1996) E7 protein of human papilloma virus-16 induces degradation of retinoblastoma protein through the ubiquitin-proteasome pathway. Cancer Res 56:4620–4624PubMedGoogle Scholar
  20. Brake T, Lambert PF (2005) Estrogen contributes to the onset, persistence, and malignant progression of cervical cancer in a human papillomavirus-transgenic mouse model. Proc Natl Acad Sci U S A 102:2490–2495PubMedCentralPubMedGoogle Scholar
  21. Brehm A, Nielsen SJ, Miska EA, McCance DJ, Reid JL, Bannister AJ et al (1999) The E7 oncoprotein associates with Mi2 and histone deacetylase activity to promote cell growth. EMBO J 18:2449–2458PubMedCentralPubMedGoogle Scholar
  22. Byg LM, Vidlund J, Vasiljevic N, Clausen D, Forslund O, Norrild B (2012) NF-kappaB signalling is attenuated by the E7 protein from cutaneous human papillomaviruses. Virus Res 169:48–53PubMedGoogle Scholar
  23. Campo MS, Graham SV, Cortese MS, Ashrafi GH, Araibi EH, Dornan ES et al (2010) HPV-16 E5 down-regulates expression of surface HLA class I and reduces recognition by CD8 T cells. Virology 407:137–142PubMedGoogle Scholar
  24. Carro MS, Spiga FM, Quarto M, Di Ninni V, Volorio S, Alcalay M et al (2006) DEK Expression is controlled by E2F and deregulated in diverse tumor types. Cell Cycle 5:1202–1207PubMedGoogle Scholar
  25. Chaurushiya MS, Weitzman MD (2009) Viral manipulation of DNA repair and cell cycle checkpoints. DNA Repair (Amst) 8:1166–1176Google Scholar
  26. Chen SL, Lin ST, Tsai TC, Hsiao WC, Tsao YP (2007) ErbB4 (JM-b/CYT-1)-induced expression and phosphorylation of c-Jun is abrogated by human papillomavirus type 16 E5 protein. Oncogene 26:42–53PubMedGoogle Scholar
  27. Chen SL, Lin YK, Li LY, Tsao YP, Lo HY, Wang WB et al (1996) E5 proteins of human papillomavirus types 11 and 16 transactivate the c-fos promoter through the NF1 binding element. J Virol 70:8558–8563PubMedCentralPubMedGoogle Scholar
  28. Cheng L, Zhang J, Ahmad S, Rozier L, Yu H, Deng H et al (2011) Aurora B regulates formin mDia3 in achieving metaphase chromosome alignment. Dev Cell 20:342–352PubMedGoogle Scholar
  29. Cheng S, Schmidt-Grimminger DC, Murant T, Broker TR, Chow LT (1995) Differentiation-dependent up-regulation of the human papillomavirus E7 gene reactivates cellular DNA replication in suprabasal differentiated keratinocytes. Genes Dev 9:2335–2349PubMedGoogle Scholar
  30. Cho YS, Kang JW, Cho M, Cho CW, Lee S, Choe YK et al (2001) Down modulation of IL-18 expression by human papillomavirus type 16 E6 oncogene via binding to IL-18. FEBS Lett 501:139–145PubMedGoogle Scholar
  31. Conrad M, Bubb VJ, Schlegel R (1993) The human papillomavirus type 6 and 16 E5 proteins are membrane-associated proteins which associate with the 16-kilodalton pore-forming protein. J Virol 67:6170–6178PubMedCentralPubMedGoogle Scholar
  32. Conrad M, Goldstein D, Andresson T, Schlegel R (1994) The E5 protein of HPV-6, but not HPV-16, associates efficiently with cellular growth factor receptors. Virology 200:796–800PubMedGoogle Scholar
  33. Crusius K, Kaszkin M, Kinzel V, Alonso A (1999) The human papillomavirus type 16 E5 protein modulates phospholipase C-gamma-1 activity and phosphatidyl inositol turnover in mouse fibroblasts. Oncogene 18:6714–6718PubMedGoogle Scholar
  34. Crusius K, Rodriguez I, Alonso A (2000) The human papillomavirus type 16 E5 protein modulates ERK1/2 and p38 MAP kinase activation by an EGFR-independent process in stressed human keratinocytes. Virus Genes 20:65–69PubMedGoogle Scholar
  35. D’Andrea AD, Grompe M (2003) The Fanconi anaemia/BRCA pathway. Nat Rev Cancer 3:23–34PubMedGoogle Scholar
  36. Desaintes C, Demeret C, Goyat S, Yaniv M, Thierry F (1997) Expression of the papillomavirus E2 protein in HeLa cells leads to apoptosis. EMBO J 16:504–514PubMedCentralPubMedGoogle Scholar
  37. Desaintes C, Goyat S, Garbay S, Yaniv M, Thierry F (1999) Papillomavirus E2 induces p53-independent apoptosis in HeLa cells. Oncogene 18:4538–4545PubMedGoogle Scholar
  38. Deshpande A, Sicinski P, Hinds PW (2005) Cyclins and cdks in development and cancer: a perspective. Oncogene 24:2909–2915PubMedGoogle Scholar
  39. Di Domenico F, Foppoli C, Blarzino C, Perluigi M, Paolini F, Morici S et al (2009) Expression of human papilloma virus type 16 E5 protein in amelanotic melanoma cells regulates endo-cellular pH and restores tyrosinase activity. J Exp Clin Cancer Res 28:4PubMedCentralPubMedGoogle Scholar
  40. DiMaio D, Petti LM (2013) The E5 proteins. Virology 445:99–114PubMedCentralPubMedGoogle Scholar
  41. Dowhanick JJ, Mcbride AA, Howley PM (1995) Suppression of Cellular Proliferation by the Papillomavirus E2 Protein. J Virol 69:7791–7799PubMedCentralPubMedGoogle Scholar
  42. Du M, Fan X, Hong E, Chen JJ (2002) Interaction of oncogenic papillomavirus E6 proteins with fibulin-1. Biochem Biophys Res Commun 296:962–969PubMedGoogle Scholar
  43. Duensing A, Liu Y, Perdreau SA, Kleylein-Sohn J, Nigg EA, Duensing S (2007) Centriole overduplication through the concurrent formation of multiple daughter centrioles at single maternal templates. Oncogene 26:6280–6288PubMedCentralPubMedGoogle Scholar
  44. Duensing S, Duensing A, Crum CP, Munger K (2001a) Human papillomavirus type 16 E7 oncoprotein-induced abnormal centrosome synthesis is an early event in the evolving malignant phenotype. Cancer Res 61:2356–2360PubMedGoogle Scholar
  45. Duensing S, Duensing A, Flores ER, Do A, Lambert PF, Munger K (2001b) Centrosome abnormalities and genomic instability by episomal expression of human papillomavirus type 16 in raft cultures of human keratinocytes. J Virol 75:7712–7716PubMedCentralPubMedGoogle Scholar
  46. Duensing S, Lee LY, Duensing A, Basile J, Piboonniyom S, Gonzalez S et al (2000) The human papillomavirus type 16 E6 and E7 oncoproteins cooperate to induce mitotic defects and genomic instability by uncoupling centrosome duplication from the cell division cycle. Proc Natl Acad Sci U S A 97:10002–10007PubMedCentralPubMedGoogle Scholar
  47. Duensing S, Munger K (2002) The human papillomavirus type 16 E6 and E7 oncoproteins independently induce numerical and structural chromosome instability. Cancer Res 62:7075–7082PubMedGoogle Scholar
  48. Duensing S, Munger K (2003) Human papillomavirus type 16 E7 oncoprotein can induce abnormal centrosome duplication through a mechanism independent of inactivation of retinoblastoma protein family members. J Virol 77:12331–12335PubMedCentralPubMedGoogle Scholar
  49. Dyson N (1998) The regulation of E2F by pRB-family proteins. Genes Dev 12:2245–2262PubMedGoogle Scholar
  50. Dyson N, Howley PM, Munger K, Harlow E (1989) The human papilloma virus-16 E7 oncoprotein is able to bind to the retinoblastoma gene product. Science 243:934–937PubMedGoogle Scholar
  51. Espinosa AM, Alfaro A, Roman-Basaure E, Guardado-Estrada M, Palma I, Serralde C et al (2013) Mitosis is a source of potential markers for screening and survival and therapeutic targets in cervical cancer. PLoS ONE 8:e55975PubMedCentralPubMedGoogle Scholar
  52. Fan X, Liu Y, Heilman SA, Chen JJ (2013) Human papillomavirus E7 induces rereplication in response to DNA damage. J Virol 87:1200–1210PubMedCentralPubMedGoogle Scholar
  53. Filippova M, Parkhurst L, Duerksen-Hughes PJ (2004) The human papillomavirus 16 E6 protein binds to Fas-associated death domain and protects cells from Fas-triggered apoptosis. J Biol Chem 279:25729–25744PubMedGoogle Scholar
  54. Filippova M, Song H, Connolly JL, Dermody TS, Duerksen-Hughes PJ (2002) The human papillomavirus 16 E6 protein binds to tumor necrosis factor (TNF) R1 and protects cells from TNF-induced apoptosis. J Biol Chem 277:21730–21739PubMedGoogle Scholar
  55. Fischer M, Quaas M, Wintsche A, Muller GA, Engeland K (2014) Polo-like kinase 4 transcription is activated via CRE and NRF1 elements, repressed by DREAM through CDE/CHR sites and deregulated by HPV E7 protein. Nucleic Acids Res 42:163–180PubMedCentralPubMedGoogle Scholar
  56. Freire R, van Vugt MA, Mamely I, Medema RH (2006) Claspin: timing the cell cycle arrest when the genome is damaged. Cell Cycle 5:2831–2834PubMedGoogle Scholar
  57. French D, Belleudi F, Mauro MV, Mazzetta F, Raffa S, Fabiano V et al (2013) Expression of HPV16 E5 down-modulates the TGFbeta signaling pathway. Mol Cancer 12:38PubMedCentralPubMedGoogle Scholar
  58. Funk JO, Waga S, Harry JB, Espling E, Stillman B, Galloway DA (1997) Inhibition of CDK activity and PCNA-dependent DNA replication by p21 is blocked by interaction with the HPV-16 E7 oncoprotein. Genes Dev 11:2090–2100PubMedCentralPubMedGoogle Scholar
  59. Gao GF, Jakobsen BK (2000) Molecular interactions of coreceptor CD8 and MHC class I: the molecular basis for functional coordination with the T-cell receptor. Immunol Today 21:630–636PubMedGoogle Scholar
  60. Garnett TO, Duerksen-Hughes PJ (2006) Modulation of apoptosis by human papillomavirus (HPV) oncoproteins. Arch Virol 151:2321–2335PubMedCentralPubMedGoogle Scholar
  61. Garnett TO, Filippova M, Duerksen-Hughes PJ (2006) Accelerated degradation of FADD and procaspase 8 in cells expressing human papilloma virus 16 E6 impairs TRAIL-mediated apoptosis. Cell Death Differ 13:1915–1926PubMedCentralPubMedGoogle Scholar
  62. Genther Williams SM, Disbrow GL, Schlegel R, Lee D, Threadgill DW, Lambert PF (2005) Requirement of epidermal growth factor receptor for hyperplasia induced by E5, a high-risk human papillomavirus oncogene. Cancer Res 65:6534–6542PubMedGoogle Scholar
  63. Gewin L, Myers H, Kiyono T, Galloway DA (2004) Identification of a novel telomerase repressor that interacts with the human papillomavirus type-16 E6/E6-AP complex. Genes Dev 18:2269–2282PubMedCentralPubMedGoogle Scholar
  64. Gillespie KA, Mehta KP, Laimins LA, Moody CA (2012) Human papillomaviruses recruit cellular DNA repair and homologous recombination factors to viral replication centers. J Virol 86:9520–9526PubMedCentralPubMedGoogle Scholar
  65. Gillison ML, Koch WM, Capone RB, Spafford M, Westra WH, Wu L et al (2000) Evidence for a causal association between human papillomavirus and a subset of head and neck cancers. J Natl Cancer Inst 92:709–720PubMedGoogle Scholar
  66. Goel HL, Mercurio AM (2013) VEGF targets the tumour cell. Nat Rev Cancer 13:871–882PubMedCentralPubMedGoogle Scholar
  67. Goodwin EC, 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 97:12513–12518PubMedCentralPubMedGoogle Scholar
  68. Gross-Mesilaty S, Reinstein E, Bercovich B, Tobias KE, Schwartz AL, Kahana C et al (1998) Basal and human papillomavirus E6 oncoprotein-induced degradation of Myc proteins by the ubiquitin pathway. Proc Natl Acad Sci U S A 95:8058–8063PubMedCentralPubMedGoogle Scholar
  69. Gruener M, Bravo IG, Momburg F, Alonso A, Tomakidi P (2007) The E5 protein of the human papillomavirus type 16 down-regulates HLA-I surface expression in calnexin-expressing but not in calnexin-deficient cells. Virol J 4:116PubMedCentralPubMedGoogle Scholar
  70. Guarguaglini G, Duncan PI, Stierhof YD, Holmstrom T, Duensing S, Nigg EA (2005) The forkhead-associated domain protein Cep170 interacts with Polo-like kinase 1 and serves as a marker for mature centrioles. Mol Biol Cell 16:1095–1107PubMedCentralPubMedGoogle Scholar
  71. Halbert CL, Demers GW, Galloway DA (1991) The E7 gene of human papillomavirus type 16 is sufficient for immortalization of human epithelial cells. J Virol 65:473–478PubMedCentralPubMedGoogle Scholar
  72. Hanahan D, Weinberg Robert A (2011) Hallmarks of Cancer: The Next Generation. Cell 144:646–674PubMedGoogle Scholar
  73. Hawley-Nelson P, Vousden KH, Hubbert NL, Lowy DR, Schiller JT (1989) HPV16 E6 and E7 proteins cooperate to immortalize human foreskin keratinocytes. EMBO J 8:3905–3910PubMedCentralPubMedGoogle Scholar
  74. Hebner CM, Wilson R, Rader J, Bidder M, Laimins LA (2006) Human papillomaviruses target the double-stranded RNA protein kinase pathway. J Gen Virol 87:3183–3193PubMedGoogle Scholar
  75. Heilman SA, Nordberg JJ, Liu Y, Sluder G, Chen JJ (2009) Abrogation of the postmitotic checkpoint contributes to polyploidization in human papillomavirus E7-expressing cells. J Virol 83:2756–2764PubMedCentralPubMedGoogle Scholar
  76. Helfer CM, Wang R, You J (2013) Analysis of the papillomavirus E2 and bromodomain protein Brd4 interaction using bimolecular fluorescence complementation. PLoS ONE 8:e77994PubMedCentralPubMedGoogle Scholar
  77. Hellner K, Mar J, Fang F, Quackenbush J, Munger K (2009) HPV16 E7 oncogene expression in normal human epithelial cells causes molecular changes indicative of an epithelial to mesenchymal transition. Virology 391:57–63PubMedCentralPubMedGoogle Scholar
  78. Hong S, Laimins LA (2013) The JAK-STAT Transcriptional Regulator, STAT-5, Activates the ATM DNA Damage Pathway to Induce HPV 31 Genome Amplification upon Epithelial Differentiation. PLoS Pathog 9:e1003295PubMedCentralPubMedGoogle Scholar
  79. Hoskins EE, Gunawardena RW, Habash KB, Wise-Draper TM, Jansen M, Knudsen ES et al (2008) Coordinate regulation of Fanconi anemia gene expression occurs through the Rb/E2F pathway. Oncogene 27:4798–4808PubMedCentralPubMedGoogle Scholar
  80. Hoskins EE, Morreale RJ, Werner SP, Higginbotham JM, Laimins LA, Lambert PF et al (2012) The fanconi anemia pathway limits human papillomavirus replication. J Virol 86:8131–8138PubMedCentralPubMedGoogle Scholar
  81. Hoskins EE, Morris TA, Higginbotham JM, Spardy N, Cha E, Kelly P et al (2009) Fanconi anemia deficiency stimulates HPV-associated hyperplastic growth in organotypic epithelial raft culture. Oncogene 28:674–685PubMedCentralPubMedGoogle Scholar
  82. Hovest MG, Krieg T, Herrmann G (2011) Differential roles for Chk1 and FANCD2 in ATR-mediated signalling for psoralen photoactivation-induced senescence. Exp Dermatol 20:883–889PubMedGoogle Scholar
  83. Huang SM, McCance DJ (2002) Down regulation of the interleukin-8 promoter by human papillomavirus type 16 E6 and E7 through effects on CREB binding protein/p300 and P/CAF. J Virol 76:8710–8721PubMedCentralPubMedGoogle Scholar
  84. Huh KW, DeMasi J, Ogawa H, Nakatani Y, Howley PM, Munger K (2005) Association of the human papillomavirus type 16 E7 oncoprotein with the 600-kDa retinoblastoma protein-associated factor, p600. Proc Natl Acad Sci U S A 102:11492–11497PubMedCentralPubMedGoogle Scholar
  85. Hwang ES, Nottoli T, Dimaio D (1995) The HPV16 E5 protein: expression, detection, and stable complex formation with transmembrane proteins in COS cells. Virology 211:227–233PubMedGoogle Scholar
  86. Hwang SG, Lee D, Kim J, Seo T, Choe J (2002) Human papillomavirus type 16 E7 binds to E2F1 and activates E2F1-driven transcription in a retinoblastoma protein-independent manner. J Biol Chem 277:2923–2930PubMedGoogle Scholar
  87. Iftner T, Elbel M, Schopp B, Hiller T, Loizou JI, Caldecott KW et al (2002) Interference of papillomavirus E6 protein with single-strand break repair by interaction with XRCC1. EMBO J 21:4741–4748PubMedCentralPubMedGoogle Scholar
  88. Jeon S, Allen-Hoffmann BL, Lambert PF (1995) Integration of human papillomavirus type 16 into the human genome correlates with a selective growth advantage of cells. J Virol 69:2989–2997PubMedCentralPubMedGoogle Scholar
  89. Jones DL, Alani RM, Munger K (1997) The human papillomavirus E7 oncoprotein can uncouple cellular differentiation and proliferation in human keratinocytes by abrogating p21Cip1-mediated inhibition of cdk2. Genes Dev 11:2101–2111PubMedCentralPubMedGoogle Scholar
  90. Jung YS, Kato I, Kim HR (2013) A novel function of HPV16-E6/E7 in epithelial-mesenchymal transition. Biochem Biophys Res Commun 435:339–344PubMedGoogle Scholar
  91. Kanno T, Kanno Y, Siegel RM, Jang MK, Lenardo MJ, Ozato K (2004) Selective recognition of acetylated histones by bromodomain proteins visualized in living cells. Mol Cell 13:33–43PubMedGoogle Scholar
  92. Katich SC, Zerfass-Thome K, Hoffmann I (2001) Regulation of the Cdc25A gene by the human papillomavirus Type 16 E7 oncogene. Oncogene 20:543–550PubMedGoogle Scholar
  93. Katzenellenbogen RA, Vliet-Gregg P, Xu M, Galloway DA (2009) NFX1-123 increases hTERT expression and telomerase activity posttranscriptionally in human papillomavirus type 16 E6 keratinocytes. J Virol 83:6446–6456PubMedCentralPubMedGoogle Scholar
  94. Kaur P, McDougall JK (1988) Characterization of primary human keratinocytes transformed by human papillomavirus type 18. J Virol 62:1917–1924PubMedCentralPubMedGoogle Scholar
  95. Kavanaugh GM, Wise-Draper TM, Morreale RJ, Morrison MA, Gole B, Schwemberger S et al (2011) The human DEK oncogene regulates DNA damage response signaling and repair. Nucleic Acids Res 39:7465–7476PubMedCentralPubMedGoogle Scholar
  96. Kaverina I, Krylyshkina O, Small JV (2002) Regulation of substrate adhesion dynamics during cell motility. Int J Biochem Cell Biol 34:746–761PubMedGoogle Scholar
  97. Kim SH, Juhnn YS, Kang S, Park SW, Sung MW, Bang YJ et al (2006) Human papillomavirus 16 E5 up-regulates the expression of vascular endothelial growth factor through the activation of epidermal growth factor receptor, MEK/ ERK1,2 and PI3 K/Akt. Cell Mol Life Sci 63:930–938PubMedGoogle Scholar
  98. Kim SH, Oh JM, No JH, Bang YJ, Juhnn YS, Song YS (2009) Involvement of NF-kappaB and AP-1 in COX-2 upregulation by human papillomavirus 16 E5 oncoprotein. Carcinogenesis 30:753–757PubMedGoogle Scholar
  99. Kimple RJ, Smith MA, Blitzer GC, Torres AD, Martin JA, Yang RZ et al (2013) Enhanced radiation sensitivity in HPV-positive head and neck cancer. Cancer Res 73:4791–4800PubMedCentralPubMedGoogle Scholar
  100. Kivi N, Greco D, Auvinen P, Auvinen E (2008) Genes involved in cell adhesion, cell motility and mitogenic signaling are altered due to HPV 16 E5 protein expression. Oncogene 27:2532–2541PubMedGoogle Scholar
  101. Kleine-Lowinski K, Rheinwald JG, Fichorova RN, Anderson DJ, Basile J, Munger K et al (2003) Selective suppression of monocyte chemoattractant protein-1 expression by human papillomavirus E6 and E7 oncoproteins in human cervical epithelial and epidermal cells. Int J Cancer 107:407–415PubMedGoogle Scholar
  102. Klingelhutz AJ, Foster SA, McDougall JK (1996) Telomerase activation by the E6 gene product of human papillomavirus type 16. Nature 380:79–82PubMedGoogle Scholar
  103. Korzeniewski N, Spardy N, Duensing A, Duensing S (2011a) Genomic instability and cancer: lessons learned from human papillomaviruses. Cancer Lett 305:113–122PubMedCentralPubMedGoogle Scholar
  104. Korzeniewski N, Treat B, Duensing S (2011b) The HPV-16 E7 oncoprotein induces centriole multiplication through deregulation of Polo-like kinase 4 expression. Mol Cancer 10:61PubMedCentralPubMedGoogle Scholar
  105. Kottemann MC, Smogorzewska A (2013) Fanconi anaemia and the repair of Watson and Crick DNA crosslinks. Nature 493:356–363PubMedCentralPubMedGoogle Scholar
  106. Kreimer AR, Clifford GM, Boyle P, Franceschi S (2005) Human papillomavirus types in head and neck squamous cell carcinomas worldwide: a systematic review. Cancer Epidemiol Biomarkers Prev 14:467–475PubMedGoogle Scholar
  107. Kutler DI, Wreesmann VB, Goberdhan A, Ben-Porat L, Satagopan J, Ngai I et al (2003) Human papillomavirus DNA and p53 polymorphisms in squamous cell carcinomas from Fanconi anemia patients. J Natl Cancer Inst 95:1718–1721PubMedGoogle Scholar
  108. Lai D, Tan CL, Gunaratne J, Quek LS, Nei W, Thierry F et al (2013) Localization of HPV-18 E2 at mitochondrial membranes induces ROS release and modulates host cell metabolism. PLoS ONE 8:e75625PubMedCentralPubMedGoogle Scholar
  109. Lee AY, Chiang CM (2009) Chromatin adaptor Brd4 modulates E2 transcription activity and protein stability. J Biol Chem 284:2778–2786PubMedCentralPubMedGoogle Scholar
  110. Lee SS, Glaunsinger B, Mantovani F, Banks L, Javier RT (2000) Multi-PDZ domain protein MUPP1 is a cellular target for both adenovirus E4-ORF1 and high-risk papillomavirus type 18 E6 oncoproteins. J Virol 74:9680–9693PubMedCentralPubMedGoogle Scholar
  111. Leechanachai P, Banks L, Moreau F, Matlashewski G (1992) The E5 gene from human papillomavirus type 16 is an oncogene which enhances growth factor-mediated signal transduction to the nucleus. Oncogene 7:19–25PubMedGoogle Scholar
  112. Leptak C, Ramon y Cajal S, Kulke R, Kulke R, Horwitz BH, Riese DJ, Dotto GP et al (1991) Tumorigenic transformation of murine keratinocytes by the E5 genes of bovine papillomavirus type 1 and human papillomavirus type 16. J Virol 65:7078–7083PubMedCentralPubMedGoogle Scholar
  113. Liao S, Deng D, Hu X, Wang W, Li L, Li W et al (2013a) HPV16/18 E5, a promising candidate for cervical cancer vaccines, affects SCPs, cell proliferation and cell cycle, and forms a potential network with E6 and E7. Int J Mol Med 31:120–128PubMedGoogle Scholar
  114. Liao S, Deng D, Zhang W, Hu X, Wang W, Wang H et al (2013b) Human papillomavirus 16/18 E5 promotes cervical cancer cell proliferation, migration and invasion in vitro and accelerates tumor growth in vivo. Oncol Rep 29:95–102PubMedGoogle Scholar
  115. Liu X, Dakic A, Zhang Y, Dai Y, Chen R, Schlegel R (2009) HPV E6 protein interacts physically and functionally with the cellular telomerase complex. Proc Natl Acad Sci U S A 106:18780–18785PubMedCentralPubMedGoogle Scholar
  116. Liu Y, Heilman SA, Illanes D, Sluder G, Chen JJ (2007) p53-independent abrogation of a postmitotic checkpoint contributes to human papillomavirus E6-induced polyploidy. Cancer Res 67:2603–2610PubMedGoogle Scholar
  117. Loncarek J, Hergert P, Magidson V, Khodjakov A (2008) Control of daughter centriole formation by the pericentriolar material. Nat Cell Biol 10:322–328PubMedCentralPubMedGoogle Scholar
  118. Machida YJ, Dutta A (2007) The APC/C inhibitor, Emi1, is essential for prevention of rereplication. Genes Dev 21:184–194PubMedCentralPubMedGoogle Scholar
  119. Massimi P, Shai A, Lambert P, Banks L (2008) HPV E6 degradation of p53 and PDZ containing substrates in an E6AP null background. Oncogene 27:1800–1804PubMedGoogle Scholar
  120. Matsukura T, Koi S, Sugase M (1989) Both episomal and integrated forms of human papillomavirus type 16 are involved in invasive cervical cancers. Virology 172:63–72PubMedGoogle Scholar
  121. McKenna DJ, Patel D, McCance DJ (2014) miR-24 and miR-205 expression is dependent on HPV onco-protein expression in keratinocytes. Virology 448:210–216PubMedCentralPubMedGoogle Scholar
  122. McLaughlin-Drubin ME, Huh KW, Munger K (2008) Human papillomavirus type 16 E7 oncoprotein associates with E2F6. J Virol 82:8695–8705PubMedCentralPubMedGoogle Scholar
  123. McMurray HR, McCance DJ (2003) Human papillomavirus type 16 E6 activates TERT gene transcription through induction of c-Myc and release of USF-mediated repression. J Virol 77:9852–9861PubMedCentralPubMedGoogle Scholar
  124. Mihaylov IS, Kondo T, Jones L, Ryzhikov S, Tanaka J, Zheng J et al (2002) Control of DNA replication and chromosome ploidy by geminin and cyclin A. Mol Cell Biol 22:1868–1880PubMedCentralPubMedGoogle Scholar
  125. Mileo AM, Abbruzzese C, Vico C, Bellacchio E, Matarrese P, Ascione B et al (2013) The human papillomavirus-16 E7 oncoprotein exerts antiapoptotic effects via its physical interaction with the actin-binding protein gelsolin. Carcinogenesis 34:2424–2433PubMedGoogle Scholar
  126. Miura S, Kawana K, Schust DJ, Fujii T, Yokoyama T, Iwasawa Y et al (2010) CD1d, a sentinel molecule bridging innate and adaptive immunity, is downregulated by the human papillomavirus (HPV) E5 protein: a possible mechanism for immune evasion by HPV. J Virol 84:11614–11623PubMedCentralPubMedGoogle Scholar
  127. Moody CA, Laimins LA (2010) Human papillomavirus oncoproteins: pathways to transformation. Nat Rev Cancer 10:550–560PubMedGoogle Scholar
  128. Moody CA, Laimins LA (2009) Human papillomaviruses activate the ATM DNA damage pathway for viral genome amplification upon differentiation. PLoS Pathog 5:e1000605PubMedCentralPubMedGoogle Scholar
  129. Muller M, Demeret C (2014) CCHCR1 Interacts Specifically with the E2 Protein of Human Papillomavirus Type 16 on a Surface Overlapping BRD4 Binding. PLoS ONE 9:e92581PubMedCentralPubMedGoogle Scholar
  130. Munger K, Phelps WC, Bubb V, Howley PM, Schlegel R (1989) The E6 and E7 genes of the human papillomavirus type 16 together are necessary and sufficient for transformation of primary human keratinocytes. J Virol 63:4417–4421PubMedCentralPubMedGoogle Scholar
  131. Nguyen CL, Eichwald C, Nibert ML, Munger K (2007) Human papillomavirus type 16 E7 oncoprotein associates with the centrosomal component gamma-tubulin. J Virol 81:13533–13543PubMedCentralPubMedGoogle Scholar
  132. Nguyen CL, Munger K (2008) Direct association of the HPV16 E7 oncoprotein with cyclin A/CDK2 and cyclin E/CDK2 complexes. Virology 380:21–25PubMedCentralPubMedGoogle Scholar
  133. Nguyen DX, Westbrook TF, McCance DJ (2002) Human papillomavirus type 16 E7 maintains elevated levels of the cdc25A tyrosine phosphatase during deregulation of cell cycle arrest. J Virol 76:619–632PubMedCentralPubMedGoogle Scholar
  134. Niebler M, Qian X, Hofler D, Kogosov V, Kaewprag J, Kaufmann AM et al (2013) Post-translational control of IL-1beta via the human papillomavirus type 16 E6 oncoprotein: a novel mechanism of innate immune escape mediated by the E3-ubiquitin ligase E6-AP and p53. PLoS Pathog 9:e1003536PubMedCentralPubMedGoogle Scholar
  135. Nishimura A, Ono T, Ishimoto A, Dowhanick JJ, Frizzell MA, Howley PM et al (2000) Mechanisms of human papillomavirus E2-mediated repression of viral oncogene expression and cervical cancer cell growth inhibition. J Virol 74:3752–3760PubMedCentralPubMedGoogle Scholar
  136. Oh JM, Kim SH, Cho EA, Song YS, Kim WH, Juhnn YS (2010) Human papillomavirus type 16 E5 protein inhibits hydrogen-peroxide-induced apoptosis by stimulating ubiquitin-proteasome-mediated degradation of Bax in human cervical cancer cells. Carcinogenesis 31:402–410PubMedGoogle Scholar
  137. Oh JM, Kim SH, Lee YI, Seo M, Kim SY, Song YS et al (2009) Human papillomavirus E5 protein induces expression of the EP4 subtype of prostaglandin E2 receptor in cyclic AMP response element-dependent pathways in cervical cancer cells. Carcinogenesis 30:141–149PubMedGoogle Scholar
  138. Park JW, Shin MK, and Lambert PF (2013) High incidence of female reproductive tract cancers in FA-deficient HPV16-transgenic mice correlates with E7’s induction of DNA damage response, an activity mediated by E7’s inactivation of pocket proteins. Oncogene Google Scholar
  139. Patel D, Huang SM, Baglia LA, McCance DJ (1999) The E6 protein of human papillomavirus type 16 binds to and inhibits co-activation by CBP and p300. EMBO J 18:5061–5072PubMedCentralPubMedGoogle Scholar
  140. Patel D, McCance DJ (2010) Compromised spindle assembly checkpoint due to altered expression of Ubch10 and Cdc20 in human papillomavirus type 16 E6- and E7-expressing keratinocytes. J Virol 84:10956–10964PubMedCentralPubMedGoogle Scholar
  141. Paulsson K, Wang P (2003) Chaperones and folding of MHC class I molecules in the endoplasmic reticulum. Biochim Biophys Acta 1641:1–12PubMedGoogle Scholar
  142. Pedroza-Saavedra A, Lam EW, Esquivel-Guadarrama F, Gutierrez-Xicotencatl L (2010) The human papillomavirus type 16 E5 oncoprotein synergizes with EGF-receptor signaling to enhance cell cycle progression and the down-regulation of p27(Kip1). Virology 400:44–52PubMedGoogle Scholar
  143. Pim D, Collins M, Banks L (1992) Human papillomavirus type 16 E5 gene stimulates the transforming activity of the epidermal growth factor receptor. Oncogene 7:27–32PubMedGoogle Scholar
  144. Pim D, Thomas M, Javier R, Gardiol D, Banks L (2000) HPV E6 targeted degradation of the discs large protein: evidence for the involvement of a novel ubiquitin ligase. Oncogene 19:719–725PubMedGoogle Scholar
  145. Regan JA, Laimins LA (2008) Bap31 is a novel target of the human papillomavirus E5 protein. J Virol 82:10042–10051PubMedCentralPubMedGoogle Scholar
  146. Reuter S, Bartelmann M, Vogt M, Geisen C, Napierski I, Kahn T, Delius H, Lichter Pm Weitz S, Korn B, Schwarz E (1998) APM-1, a novel human gene, identified by aberrant co-transcription with papillomavirus oncogenes in a cervical carcinoma cell line, encodes a BTB/POZ-zinc finger protein with growth inhibitory activity. EMBO J 17(1):215−222Google Scholar
  147. Rey O, Lee S, Park NH (2000) Human papillomavirus type 16 E7 oncoprotein represses transcription of human fibronectin. J Virol 74:4912–4918PubMedCentralPubMedGoogle Scholar
  148. Riaz N, Sherman EJ, Fury M, Lee N (2013) Should cetuximab replace Cisplatin for definitive chemoradiotherapy in locally advanced head and neck cancer? J Clin Oncol 31:287–288PubMedGoogle Scholar
  149. Ricciotti E, FitzGerald GA (2011) Prostaglandins and inflammation. Arterioscler Thromb Vasc Biol 31:986–1000PubMedCentralPubMedGoogle Scholar
  150. Richards KH, Doble R, Wasson CW, Haider M, Blair GE, Wittmann M et al (2014) Human papillomavirus e7 oncoprotein increases production of the anti-inflammatory interleukin-18 binding protein in keratinocytes. J Virol 88:4173–4179PubMedCentralPubMedGoogle Scholar
  151. Rieckmann T, Tribius S, Grob TJ, Meyer F, Busch CJ, Petersen C et al. (2013) HNSCC cell lines positive for HPV and p16 possess higher cellular radiosensitivity due to an impaired DSB repair capacity. Radiother Oncol Google Scholar
  152. Riley RR, Duensing S, Brake T, Munger K, Lambert PF, Arbeit JM (2003) Dissection of human papillomavirus E6 and E7 function in transgenic mouse models of cervical carcinogenesis. Cancer Res 63:4862–4871PubMedGoogle Scholar
  153. Romick-Rosendale LE, Lui VW, Grandis JR, Wells SI (2013) The Fanconi anemia pathway: repairing the link between DNA damage and squamous cell carcinoma. Mutat Res 743–744:78–88PubMedGoogle Scholar
  154. Ronco LV, Karpova AY, Vidal M, Howley PM (1998) Human papillomavirus 16 E6 oncoprotein binds to interferon regulatory factor-3 and inhibits its transcriptional activity. Genes Dev 12:2061–2072PubMedCentralPubMedGoogle Scholar
  155. Rossjohn J, Pellicci DG, Patel O, Gapin L, Godfrey DI (2012) Recognition of CD1d-restricted antigens by natural killer T cells. Nat Rev Immunol 12:845–857PubMedCentralPubMedGoogle Scholar
  156. Sadasivam S, DeCaprio JA (2013) The DREAM complex: master coordinator of cell cycle-dependent gene expression. Nat Rev Cancer 13:585–595PubMedCentralPubMedGoogle Scholar
  157. Scheffner M, Huibregtse JM, Vierstra RD, Howley PM (1993) The HPV-16 E6 and E6-AP complex functions as a ubiquitin-protein ligase in the ubiquitination of p53. Cell 75:495–505PubMedGoogle Scholar
  158. Schiffman M, Castle PE, Jeronimo J, Rodriguez AC, Wacholder S (2007) Human papillomavirus and cervical cancer. Lancet 370:890–907PubMedGoogle Scholar
  159. Schmitz M, Driesch C, Beer-Grondke K, Jansen L, Runnebaum IB, Dürst M (2012) Loss of gene function as a consequence of human papillomavirus DNA integration. Int J Cancer 131:E593−E602Google Scholar
  160. Schvartzman JM, Sotillo R, Benezra R (2010) Mitotic chromosomal instability and cancer: mouse modelling of the human disease. Nat Rev Cancer 10:102–115PubMedGoogle Scholar
  161. Schwarz E, Freese UK, Gissmann L, Mayer W, Roggenbuck B, Stremlau A et al (1985) Structure and transcription of human papillomavirus sequences in cervical carcinoma cells. Nature 314:111–114PubMedGoogle Scholar
  162. Schweiger MR, Ottinger M, You J, Howley PM (2007) Brd4-independent transcriptional repression function of the papillomavirus e2 proteins. J Virol 81:9612–9622PubMedCentralPubMedGoogle Scholar
  163. Scully C (2002) Oral squamous cell carcinoma; from an hypothesis about a virus, to concern about possible sexual transmission. Oral Oncol 38:227–234PubMedGoogle Scholar
  164. Shin KH, Ahn JH, Kang MK, Lim PK, Yip FK, Baluda MA et al (2006) HPV-16 E6 oncoprotein impairs the fidelity of DNA end-joining via p53-dependent and -independent pathways. Int J Oncol 28:209–215PubMedGoogle Scholar
  165. Shirasawa H, Tomita Y, Sekiya S, Takamizawa H, Simizu B (1987) Integration and transcription of human papillomavirus type 16 and 18 sequences in cell lines derived from cervical carcinomas. J Gen Virol 68(Pt 2):583–591PubMedGoogle Scholar
  166. Sluder G, Thompson EA, Miller FJ, Hayes J, Rieder CL (1997) The checkpoint control for anaphase onset does not monitor excess numbers of spindle poles or bipolar spindle symmetry. J Cell Sci 110(Pt 4):421–429PubMedGoogle Scholar
  167. Smith J, Tho LM, Xu N, Gillespie DA (2010a) The ATM-Chk2 and ATR-Chk1 pathways in DNA damage signaling and cancer. Adv Cancer Res 108:73–112PubMedGoogle Scholar
  168. Smith JA, White EA, Sowa ME, Powell ML, Ottinger M, Harper JW et al (2010b) Genome-wide siRNA screen identifies SMCX, EP400, and Brd4 as E2-dependent regulators of human papillomavirus oncogene expression. Proc Natl Acad Sci U S A 107:3752–3757PubMedCentralPubMedGoogle Scholar
  169. Spanos WC, Hoover A, Harris GF, Wu S, Strand GL, Anderson ME et al (2008) The PDZ binding motif of human papillomavirus type 16 E6 induces PTPN13 loss, which allows anchorage-independent growth and synergizes with ras for invasive growth. J Virol 82:2493–2500PubMedCentralPubMedGoogle Scholar
  170. Spardy N, Covella K, Cha E, Hoskins EE, Wells SI, Duensing A et al (2009) Human papillomavirus 16 E7 oncoprotein attenuates DNA damage checkpoint control by increasing the proteolytic turnover of claspin. Cancer Res 69:7022–7029PubMedCentralPubMedGoogle Scholar
  171. Spardy N, Duensing A, Charles D, Haines N, Nakahara T, Lambert PF et al (2007) The human papillomavirus type 16 E7 oncoprotein activates the Fanconi anemia (FA) pathway and causes accelerated chromosomal instability in FA cells. J Virol 81:13265–13270PubMedCentralPubMedGoogle Scholar
  172. Spardy N, Duensing A, Hoskins EE, Wells SI, Duensing S (2008) HPV-16 E7 reveals a link between DNA replication stress, fanconi anemia D2 protein, and alternative lengthening of telomere-associated promyelocytic leukemia bodies. Cancer Res 68:9954–9963PubMedCentralPubMedGoogle Scholar
  173. Stevaux O, Dyson NJ (2002) A revised picture of the E2F transcriptional network and RB function. Curr Opin Cell Biol 14:684–691PubMedGoogle Scholar
  174. Stoppler MC, Straight SW, Tsao G, Schlegel R, McCance DJ (1996) The E5 gene of HPV-16 enhances keratinocyte immortalization by full-length DNA. Virology 223:251–254PubMedGoogle Scholar
  175. Straight SW, Herman B, McCance DJ (1995) The E5 oncoprotein of human papillomavirus type 16 inhibits the acidification of endosomes in human keratinocytes. J Virol 69:3185–3192PubMedCentralPubMedGoogle Scholar
  176. Stransky N, Egloff AM, Tward AD, Kostic AD, Cibulskis K, Sivachenko A et al (2011) The mutational landscape of head and neck squamous cell carcinoma. Science 333:1157–1160PubMedCentralPubMedGoogle Scholar
  177. Sunthamala N, Thierry F, Teissier S, Pientong C, Kongyingyoes B, Tangsiriwatthana T et al (2014) E2 proteins of high risk human papillomaviruses down-modulate STING and IFN-kappa transcription in keratinocytes. PLoS ONE 9:e91473PubMedCentralPubMedGoogle Scholar
  178. Suprynowicz FA, Disbrow GL, Krawczyk E, Simic V, Lantzky K, Schlegel R (2008) HPV-16 E5 oncoprotein upregulates lipid raft components caveolin-1 and ganglioside GM1 at the plasma membrane of cervical cells. Oncogene 27:1071–1078PubMedGoogle Scholar
  179. Suprynowicz FA, Krawczyk E, Hebert JD, Sudarshan SR, Simic V, Kamonjoh CM et al (2010) The human papillomavirus type 16 E5 oncoprotein inhibits epidermal growth factor trafficking independently of endosome acidification. J Virol 84:10619–10629PubMedCentralPubMedGoogle Scholar
  180. Szalmas A, Gyongyosi E, Ferenczi A, Laszlo B, Karosi T, Csomor P et al (2013) Activation of Src, Fyn and Yes non-receptor tyrosine kinases in keratinocytes expressing human papillomavirus (HPV) type 16 E7 oncoprotein. Virol J 10:79PubMedCentralPubMedGoogle Scholar
  181. Thierry F, Heard JM, Dartmann K, Yaniv M (1987) Characterization of a transcriptional promoter of human papillomavirus 18 and modulation of its expression by simian virus 40 and adenovirus early antigens. J Virol 61:134–142PubMedCentralPubMedGoogle Scholar
  182. Thierry F, Yaniv M (1987) The BPV1-E2 trans-acting protein can be either an activator or a repressor of the HPV18 regulatory region. EMBO J 6:3391–3397PubMedCentralPubMedGoogle Scholar
  183. Thomas JT, Laimins LA (1998) Human papillomavirus oncoproteins E6 and E7 independently abrogate the mitotic spindle checkpoint. J Virol 72:1131–1137PubMedCentralPubMedGoogle Scholar
  184. Thomas M, Banks L (1998) Inhibition of Bak-induced apoptosis by HPV-18 E6. Oncogene 17:2943–2954PubMedGoogle Scholar
  185. Thomas MC, Chiang CM (2005) E6 oncoprotein represses p53-dependent gene activation via inhibition of protein acetylation independently of inducing p53 degradation. Mol Cell 17:251–264PubMedGoogle Scholar
  186. Thompson DA, Belinsky G, Chang TH, Jones DL, Schlegel R, Munger K (1997) The human papillomavirus-16 E6 oncoprotein decreases the vigilance of mitotic checkpoints. Oncogene 15:3025–3035PubMedGoogle Scholar
  187. Thomsen P, van Deurs B, Norrild B, Kayser L (2000) The HPV16 E5 oncogene inhibits endocytic trafficking. Oncogene 19:6023–6032PubMedGoogle Scholar
  188. Tiala I, Wakkinen J, Suomela S, Puolakkainen P, Tammi R, Forsberg S et al (2008) The PSORS1 locus gene CCHCR1 affects keratinocyte proliferation in transgenic mice. Hum Mol Genet 17:1043–1051PubMedGoogle Scholar
  189. Todorovic B, Nichols AC, Chitilian JM, Myers MP, Shepherd TG, Parsons SJ et al (2014) The human papillomavirus E7 proteins associate with p190RhoGAP and alter its function. J Virol 88:3653–3663PubMedCentralPubMedGoogle Scholar
  190. Tomakidi P, Cheng H, Kohl A, Komposch G, Alonso A (2000) Connexin 43 expression is downregulated in raft cultures of human keratinocytes expressing the human papillomavirus type 16 E5 protein. Cell Tissue Res 301:323–327PubMedGoogle Scholar
  191. Tsao YP, Li LY, Tsai TC, Chen SL (1996) Human papillomavirus type 11 and 16 E5 represses p21(WafI/SdiI/CipI) gene expression in fibroblasts and keratinocytes. J Virol 70:7535–7539PubMedCentralPubMedGoogle Scholar
  192. van Zeeburg HJ, Snijders PJ, Pals G, Hermsen MA, Rooimans MA, Bagby G et al (2005) Generation and molecular characterization of head and neck squamous cell lines of fanconi anemia patients. Cancer Res 65:1271–1276PubMedGoogle Scholar
  193. van Zeeburg HJ, Snijders PJ, Wu T, Gluckman E, Soulier J, Surralles J et al (2008) Clinical and molecular characteristics of squamous cell carcinomas from Fanconi anemia patients. J Natl Cancer Inst 100:1649–1653PubMedCentralPubMedGoogle Scholar
  194. Vaziri C, Saxena S, Jeon Y, Lee C, Murata K, Machida Y et al (2003) A p53-dependent checkpoint pathway prevents rereplication. Mol Cell 11:997–1008PubMedGoogle Scholar
  195. Vidal L and Gillison ML (2008) Human papillomavirus in HNSCC: recognition of a distinct disease type. Hematol Oncol Clin North Am 22, 1125–42, viiGoogle Scholar
  196. Vinokurova S, Wentzensen N, Kraus I, Klaes R, Driesch C, Melsheimer P et al (2008) Type-dependent integration frequency of human papillomavirus genomes in cervical lesions. Cancer Res 68:307–313PubMedGoogle Scholar
  197. Vousden KH, Prives C (2009) Blinded by the Light: The Growing Complexity of p53. Cell 137:413–431PubMedGoogle Scholar
  198. Wallace NA and Galloway DA (2014) Manipulation of cellular DNA damage repair machinery facilitates propagation of human papillomaviruses. Semin Cancer Biol Google Scholar
  199. Wallace NA, Robinson K, Howie HL, Galloway DA (2012) HPV 5 and 8 E6 abrogate ATR activity resulting in increased persistence of UVB induced DNA damage. PLoS Pathog 8:e1002807PubMedCentralPubMedGoogle Scholar
  200. Wang X, Helfer CM, Pancholi N, Bradner JE, You J (2013) Recruitment of Brd4 to the human papillomavirus type 16 DNA replication complex is essential for replication of viral DNA. J Virol 87:3871–3884PubMedCentralPubMedGoogle Scholar
  201. Watson RA, Thomas M, Banks L, Roberts S (2003) Activity of the human papillomavirus E6 PDZ-binding motif correlates with an enhanced morphological transformation of immortalized human keratinocytes. J Cell Sci 116:4925–4934PubMedGoogle Scholar
  202. Wells SI, Francis DA, Karpova AY, Dowhanick JJ, Benson JD, Howley PM (2000) Papillomavirus E2 induces senescence in HPV-positive cells via pRB- and p21(CIP)-dependent pathways. EMBO J 19:5762–5771PubMedCentralPubMedGoogle Scholar
  203. Westra WH (2009) The changing face of head and neck cancer in the 21st century: the impact of HPV on the epidemiology and pathology of oral cancer. Head Neck Pathol 3:78–81PubMedCentralPubMedGoogle Scholar
  204. Wetherill LF, Holmes KK, Verow M, Muller M, Howell G, Harris M et al (2012) High-risk human papillomavirus E5 oncoprotein displays channel-forming activity sensitive to small-molecule inhibitors. J Virol 86:5341–5351PubMedCentralPubMedGoogle Scholar
  205. Winkler B, Crum CP, Fujii T, Ferenczy A, Boon M, Braun L et al (1984) Koilocytotic lesions of the cervix. The relationship of mitotic abnormalities to the presence of papillomavirus antigens and nuclear DNA content. Cancer 53:1081–1087PubMedGoogle Scholar
  206. Wise-Draper TM, Draper DJ, Gutkind JS, Molinolo AA, Wikenheiser-Brokamp KA, Wells SI (2012) Future directions and treatment strategies for head and neck squamous cell carcinomas. Transl Res 160:167–177PubMedCentralPubMedGoogle Scholar
  207. Wittekindt C, Wagner S, Mayer CS, and Klussmann JP (2012) [Basics of tumor development and importance of human papilloma virus (HPV) for head and neck cancer]. Laryngorhinootologie 91 Suppl 1, S1–26Google Scholar
  208. Wu SY, Lee AY, Hou SY, Kemper JK, Erdjument-Bromage H, Tempst P et al (2006) Brd4 links chromatin targeting to HPV transcriptional silencing. Genes Dev 20:2383–2396PubMedCentralPubMedGoogle Scholar
  209. Xie X, Piao L, Bullock BN, Smith A, Su T, Zhang M et al (2014) Targeting HPV16 E6-p300 interaction reactivates p53 and inhibits the tumorigenicity of HPV-positive head and neck squamous cell carcinoma. Oncogene 33:1037–1046PubMedCentralPubMedGoogle Scholar
  210. Xue Y, Lim D, Zhi L, He P, Abastado JP, Thierry F (2012) Loss of HPV16 E2 Protein Expression Without Disruption of the E2 ORF Correlates with Carcinogenic Progression. Open Virol J 6:163–172PubMedCentralPubMedGoogle Scholar
  211. Yaginuma Y, Eguchi A, Yoshimoto M, Ogawa K (2012) The PxDLLCxE sequence in conserved region 2 of human papilloma virus 18 protein E7 is required for E7 binding to centromere protein C. Oncology 83:210–217PubMedGoogle Scholar
  212. Yim EK, Lee KH, Myeong J, Tong SY, Um SJ, Park JS (2007) Novel interaction between HPV E6 and BARD1 (BRCA1-associated ring domain 1) and its biologic roles. DNA Cell Biol 26:753–761PubMedGoogle Scholar
  213. You J, Croyle JL, Nishimura A, Ozato K, Howley PM (2004) Interaction of the bovine papillomavirus E2 protein with Brd4 tethers the viral DNA to host mitotic chromosomes. Cell 117:349–360PubMedGoogle Scholar
  214. Zerfass-Thome K, Zwerschke W, Mannhardt B, Tindle R, Botz JW, Jansen-Durr P (1996) Inactivation of the cdk inhibitor p27KIP1 by the human papillomavirus type 16 E7 oncoprotein. Oncogene 13:2323–2330PubMedGoogle Scholar
  215. Zhang B, Srirangam A, Potter DA, Roman A (2005a) HPV16 E5 protein disrupts the c-Cbl-EGFR interaction and EGFR ubiquitination in human foreskin keratinocytes. Oncogene 24:2585–2588PubMedCentralPubMedGoogle Scholar
  216. Zhang Y, Fan S, Meng Q, Ma Y, Katiyar P, Schlegel R et al (2005b) BRCA1 interaction with human papillomavirus oncoproteins. J Biol Chem 280:33165–33177PubMedGoogle Scholar
  217. Zhong ZH, Jiang WQ, Cesare AJ, Neumann AA, Wadhwa R, Reddel RR (2007) Disruption of telomere maintenance by depletion of the MRE11/RAD50/NBS1 complex in cells that use alternative lengthening of telomeres. J Biol Chem 282:29314–29322PubMedGoogle Scholar
  218. zur Hausen H (1999) Immortalization of human cells and their malignant conversion by high risk human papillomavirus genotypes. Semin Cancer Biol 9:405–411PubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Eric A. Smith
    • 1
    Email author
  • Marie C. Matrka
    • 1
  • Susanne I. Wells
    • 1
  1. 1.Cincinnati Children’s Hospital Medical CenterCincinnatiUSA

Personalised recommendations