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2005 | 52 | 4 |

Tytuł artykułu

The HPV16 E2 transcriptional regulator mode of action depends on the physical state of the viral genome

Warianty tytułu

Języki publikacji

EN

Abstrakty

EN
Human papillomavirus (HPV) infection is a major risk factor for the development of cervical cancer. The HPV-induced immortalization of epithelial cell usually requires integration of the viral DNA into the host cell genome. The integration event causes disruption of the E2 gene and this is followed by overexpression of the E6 and E7 oncoproteins. The E2 protein is a transcription factor that regulates expression of the E6 and E7 oncoproteins by binding to four sites within the viral long control region. We used an in vitro cell culture model to explore the role of the E2 protein in the transcriptional control of the HPV16 long control region. Employing transient and stable transfection experiments we simulated the episomal and integrated states of the viral genome, respectively. We show that the E2 protein up-regulates E6/E7 transcription from episomal DNA but represses it in the case of integrated DNA. The activator function of the E2 protein seems to counteract the repressive chromatin structure formed over episomal DNA. Steroid hormones and retinol also modulate oncogene transcription differently depending on the physical structure of the viral DNA. Our data suggest regulatory mechanisms involving interactions between the E2 protein and nuclear hormone receptors.

Wydawca

-

Rocznik

Tom

52

Numer

4

Opis fizyczny

p.823-832,fig.,ref.

Twórcy

  • August Cieszkowski University of Agriculture, Poznan, Poland
autor

Bibliografia

  • Agarwal C, Hembree JR, Rorke EA, Eckert RL (1994) Interferon and retinoic acid suppress the growth of human papillomavirus type 16 immortalized cervical epithelial cells, but only interferon suppresses the level of the human papillomavirus transforming oncogenes. Cancer Res 54: 2108–2112.
  • Alloul N, Sherman L (1999) Transcription-modulatory activities of differentially spliced cDNAs encoding the E2 protein of human papillomavirus type 16. J Gen Virol 80: 2461–2470.
  • Antson AA, Burns JE, Moroz OV, Scott DJ, Sanders CM, Bronstein IB, Dodson GG, Wilson KS, Maitland NJ (2000) Structure of the intact transactivation domain of the human papillomavirus E2 protein. Nature 403: 805–809.
  • Badaracco G, Venuti A, Sedati A, Marcante ML (2002) HPV16 and HPV18 in genital tumors: Significantly different levels of viral integration and correlation to tumor invasiveness. J Med Virol 67: 574–582.
  • Barbosa MS, Schlegel R (1989) The E6 and E7 genes of HPV-18 are sufficient for inducing two-stage in vitro transformation of human keratinocytes. Oncogene 4: 1529–1532.
  • Bechtold V, Beard P, Raj K (2003) Human papillomavirus type 16 E2 protein has no effect on transcription from episomal viral DNA. J Virol 77: 2021–2028.
  • Berger SL (2002) Histone modifications in transcriptional regulation. Curr Opin Genet Dev 12: 142–148.
  • Bernard B, Bailly C, Lenoir MC, Darmon M, Thierry F, Yaniv M (1989) The papillomavirus type 18 (HPV18) E2 gene product is a repressor of the HPV18 regulatory region in human keratinocytes. J Virol 63: 4317–4324.
  • Bouvard V, Storey A, Pim D, Banks L (1994) Characterization of the human papillomavirus E2 protein: evidence of trans-activation and trans-repression in cervical keratinocytes. EMBO J 13: 5451–5459.
  • Chen CM, Shyu MP, Au LC, Chu HW, Cheng WT, Choo KB (1994) Analysis of deletion of the integrated human papillomavirus 16 sequence in cervical cancer: a rapid multiplex polymerase chain reaction approach. J Med Virol 44: 206–211.
  • Choo KB, Pan CC, Han SH (1987) Integration of human papillomavirus type 16 into cellular DNA of cervical carcinoma: preferential deletion of the E2 gene and invariable retention of the long control region and the E6/E7 open reading frames. Virology 161: 259–261.
  • Choo CK, Rorke EA, Eckert RL (1995) Retinoid regulation of cell differentiation in a series of human papillomavirus type 16-immortalized human cervical epithelial cell lines. Carcinogenesis 16: 375–381.
  • Choo KB, Chen CM, Han CP, Cheng WT, Au LC (1996) Molecular analysis of cellular loci disrupted by papillomavirus 16 integration in cervical cancer: frequent viral integration in topologically destabilized and transcriptionally active chromosomal regions. J Med Virol 49: 15–22.
  • Cripe TP, Haugen TH, Turk JP, Tabatabai F, Schmid PG 3rd, Durst M, Gissmann L, Roman A, Turek LP (1987) Transcriptional regulation of the human papillomavirus- 16 E6-E7 promoter by a keratinocyte-dependent enhancer, and by viral E2 transactivator and repressor gene products: implications for cervical carcinogenesis. EMBO J 6: 3745–3753.
  • Crum CP, Symbula M, Ward BE (1989) Topography of early HPV 16 transcription in high-grade genital precancers. Am J Pathol 134: 1183–1188.
  • Daniel B, Rangarajan A, Mukherjee G, Vallikad E, Krishna S (1997) The link between integration and expression of human papillomavirus type 16 genomes and cellular changes in the evolution of cervical intraepithelial neoplastic lesions. J Gen Virol 78: 1095–1101.
  • DeFilippis RA, Goodwin EC, Wu L, DiMaio D (2003) Endogenous human papillomavirus E6 and E7 proteins differentially regulate proliferation, senescence, and apoptosis in HeLa cervical carcinoma cells. J Virol 77: 1551–1563.
  • Demeret C, Yaniv M, Thierry F (1994) The E2 transcriptional repressor can compensate for Sp1 activation of the human papillomavirus type 18 early promoter. J Virol 68: 7075–7082.
  • Demeret C, Desaintes C, Yaniv M, Thierry F (1997) Different mechanisms contribute to the E2-mediated transcriptional repression of human papillomavirus type 18 viral oncogenes. J Virol 71: 9343–9349.
  • 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: 504–514.
  • de Villiers EM (2003) Relationship between steroid hormone contraceptives and HPV, cervical intraepithelial neoplasia and cervical carcinoma. Int J Cancer 103: 705–708.
  • Dowhanick JJ, McBride AA, Howley PM (1995) Suppression of cellular proliferation by the papillomavirus E2 protein. J Virol 69: 7791–7799.
  • Durst M, Glitz D, Schneider A, zur Hausen H (1992) Human papillomavirus type 16 (HPV 16) gene expression and DNA replication in cervical neoplasia: analysis by in situ hybridization. Virology 189: 132–140.
  • Eckert RL, Agarwal C, Hembree JR, Choo CK, Sizemore N, Andreatta-van Leyen S, Rorke EA (1995) Human cervical cancer. Retinoids, interferon and human papillomavirus. Adv Exp Med Biol 375: 31–44.
  • Favre M, Breitburd F, Croissant O, Orth G (1977) Chromatin- like structures obtained after alkaline disruption of bovine and human papillomaviruses. J Virol 21: 1205–1209.
  • Flores ER, Allen-Hoffmann BL, Lee D, Lambert PF (2000) The human papillomavirus type 16 E7 oncogene is required for the productive stage of the viral life cycle. J Virol 74: 6622–6631.
  • Francis DA, Schmid SI, Howley PM (2000) Repression of the integrated papillomavirus E6/E7 promoter is required for growth suppression of cervical cancer cells. J Virol 74: 2679–2686.
  • Fry CJ, Farnham PJ (1999) Context-dependent transcriptional regulation. J Biol Chem 274: 29583–29586.
  • 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 USA 97: 12513–12518.
  • Hadaschik D, Hinterkeuser K, Oldak M, Pfister HJ, Smola-Hess S (2003) The papillomavirus E2 protein binds to and synergizes with C/EBP factors involved in keratinocyte differentiation. J Virol 77: 5253–5265.
  • Hancock R (2000) A new look at the nuclear matrix. Chromosoma 109: 219–225.
  • Higgins GD, Uzelin DM, Phillips GE, McEvoy P, Marin R, Burrell CJ (1992) Transcription patterns of human papillomavirus type 16 in genital intraepithelial neoplasia: evidence for promoter usage within the E7 open reading frame during epithelial differentiation. J Gen Virol 73: 2047–2057.
  • Hou SY, Wu SY, Chiang CM (2002) Transcriptional activity among high and low risk human papillomavirus E2 proteins correlates with E2 DNA binding. J Biol Chem 277: 45619–45629.
  • Jeong S, Stein A (1994) Micrococcal nuclease digestion of nuclei reveals extended nucleosome ladders having anomalous DNA lengths for chromatin assembled on non-replicating plasmids in transfected cells. Nucleic Acids Res 22: 370–375.
  • 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: 2989–2997.
  • Kaur P, McDougall JK (1989) HPV-18 immortalization of human keratinocytes. Virology 173: 302–310.
  • Khan MA, Canhoto AJ, Housley PR, Creek KE, Pirisi L (1997) Glucocorticoids stimulate growth of human papillomavirus type 16 (HPV16)-immortalized human keratinocytes and support HPV16-mediated immortalization without affecting the levels of HPV16 E6/E7 mRNA. Exp Cell Res 236: 304–310.
  • Khare S, Kumar KU, Tang SC, Pater MM, Pater A (1996) Up-regulation of hormone response of human papillomavirus type 16 expression and increased DNA-protein binding by consensus mutations of viral glucocorticoid response elements. J Med Virol 50: 254–262.
  • Khare S, Pater MM, Tang SC, Pater A (1997) Effect of glucocorticoid hormones on viral gene expression, growth, and dysplastic differentiation in HPV16-immortalized ectocervical cells. Exp Cell Res 232: 353–360.
  • Klimov E, Vinokourova S, Moisjak E, Rakhmanaliev E, Kobseva V, Laimins L, Kisseljov F, Sulimova G (2002) Human papillomaviruses and cervical tumours: mapping of integration sites and analysis of adjacent cellular sequences. BMC Cancer 2: 24.
  • Kovelman R, Bilter GK, Glezer E, Tsou AY, Barbosa MS (1996) Enhanced transcriptional activation by E2 proteins from the oncogenic human papillomaviruses. J Virol 70: 7549–7560.
  • Lee D, Lee B, Kim J, Kim DW, Choe J (2000) cAMP response element-binding protein-binding protein binds to human papillomavirus E2 protein and activates E2-dependent transcription. J Biol Chem 275: 7045–7051.
  • Lees E, Osborn K, Banks L, Crawford L (1990) Transformation of primary BRK cells by human papillomavirus type 16 and EJ-ras is increased by overexpression of the viral E2 protein. J Gen Virol 71: 183–193.
  • Leppard KN (1997) E4 gene function in adenovirus, adenovirus vector and adenoassociated virus infections. J Gen Virol 78: 2131–2138.
  • Longworth MS, Laimins LA (2004) Pathogenesis of human papillomaviruses in differentiating epithelia. Microbiol Mol Biol Rev 68: 362–372.
  • Matzner I, Savelyeva L, Schwab M (2003) Preferential integration of a transfected marker gene into spontaneously expressed fragile sites of a breast cancer cell line. Cancer Lett 189: 207–219.
  • McBride A, Myers G (1997) The E2 Proteins. In: Human Papillomaviruses 1997 Compendium. Myers G, Bernard HU, Delius H, eds. III: 54–73, Los Alamos National Laboratory Press, Los Alamos USA.
  • McMurray HR, Nguyen D, Westbrook TF, McAnce DJ (2001) Biology of human papillomaviruses. Int J Exp Pathol 82: 15–33.
  • Mearini G, Nielsen PE, Fackelmayer FO (2004) Localization and dynamics of small circular DNA in live mammalian nuclei. Nucleic Acids Res 32: 2642–2651.
  • Nakagawa S, Yoshikawa H, Yasugi T, Kimura M, Kawana K, Matsumoto K, Yamada M, Onda T, Taketani Y (2000) Ubiquitous presence of E6 and E7 transcripts in human papillomavirus-positive cervical carcinomas regardless of its type. J Med Virol 62: 251–258.
  • Narayanan BA, Holladay EB, Nixon DW, Mauro CT (1998) The effect of all-trans and 9-cis retinoic acid on the steady state level of HPV16 E6/E7 mRNA and cell cycle in cervical carcinoma cells. Life Sci 63: 565–573.
  • Nishimura A, Ono T, Ishimoto A, Dowhanick JJ, Frizzell MA, Howley PM, Sakai H (2000) Mechanisms of human papillomavirus E2-mediated repression of viral oncogene expression and cervical cancer cell growth inhibition. J Virol 74: 3752–3760.
  • O’Connor M, Chan SY, Bernard HU (1995) Transcription factor binding sites in the long control region of genital HPVs. In: Human Papillomaviruses 1995 Compendium. Myers G, Bernard HU, Delius H, eds. III: 21–40, Los Alamos National Laboratory Press, Los Alamos USA.
  • Park JS, Hwang ES, Park SN, Ahn HK, Um SJ, Kim CJ, Kim SJ, Namkoong SE (1997) Physical status and expression of HPV genes in cervical cancers. Gynecol Oncol 65: 121–129.
  • Parton A, Grand RJ, Biggs P, Settleman J, DiMaio D, Gallimore PH (1990) Integrated HPV 1 genomes in a human keratinocyte cell line can be transactivated by a SV40/BPV1 recombinant virus which expresses BPV1 E2 proteins. Virology 175: 508–517.
  • Pei XF, Sherman L, Sun YH, Schlegel R (1998) HPV-16 E7 protein bypasses keratinocyte growth inhibition by serum and calcium. Carcinogenesis 19: 1481–1486.
  • Pett MR, Alazawi WO, Roberts I, Dowen S, Smith DI, Stanley MA, Coleman N (2004) Acquisition of high-level chromosomal instability is associated with integration of human papillomavirus type 16 in cervical keratinocytes. Cancer Res 64: 1359–1368.
  • Phelps WC, Howley PM (1987) Transcriptional trans-activation by the human papillomavirus type 16 E2 gene product. J Virol 61: 1630–1638.
  • Romanczuk H, Howley PM (1992) Disruption of either the E1 or the E2 regulatory gene of human papillomavirus type 16 increases viral immortalization capacity. Proc Natl Acad Sci USA 89: 3159–3163.
  • Romanczuk H, Thierry F, Howley PM (1990) Mutational analysis of cis elements involved in E2 modulation of human papillomavirus type 16 P97 and type 18 P105 promoters. J Virol 64: 2849–2859.
  • Sah JF, Eckert RL, Chandraratna RA, Rorke EA (2002) Retinoids suppress epidermal growth factor-associated cell proliferation by inhibiting epidermal growth factor receptor-dependent ERK1/2 activation. J Biol Chem 277: 9728–9735.
  • Sashiyama H, Shino Y, Kawamata Y, Tomita Y, Ogawa N, Shimada H, Kobayashi S, Asano T, Ochiai T, Shirasawa H (2001) Immortalization of human esophageal keratinocytes by E6 and E7 of human papillomavirus type 16. Int J Oncol 19: 97–103.
  • Schwarz E, Freese UK, Gissmann L, Mayer W, Roggenbuck B, Stremlau A, zur Hausen H (1985) Structure and transcription of human papillomavirus sequences in cervical carcinoma cells. Nature 314: 111–114.
  • Steinwaerder DS, Carlson CA, Lieber A (2001) Human papilloma virus E6 and E7 proteins support DNA replication of adenoviruses deleted for the E1A and E1B genes. Mol Ther 4: 211–216.
  • Stunkel W, Bernard HU (1999) The chromatin structure of the long control region of human papillomavirus type 16 represses viral oncoprotein expression. J Virol 73: 1918–1930.
  • Stunkel W, Huang Z, Tan SH, O’Connor MJ, Bernard HU (2000) Nuclear matrix attachment regions of human papillomavirus type 16 repress or activate the E6 promoter, depending on the physical state of the viral DNA. J Virol 74: 2489–2501.
  • Tan SH, Leong LE, Walker PA, Bernard HU (1994) The human papillomavirus type 16 E2 transcription factor binds with low cooperativity to two flanking sites and represses the E6 promoter through displacement of Sp1 and TFIID. J Virol 68: 6411–6420.
  • Tan SH, Bartsch D, Schwarz E, Bernard HU (1998) Nuclear matrix attachment regions of human papillomavirus type 16 point toward conservation of these genomic
  • elements in all genital papillomaviruses. J Virol 72: 3610–3622.
  • 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: 3391–3397.
  • Thierry F, Benotmane MA, Demeret C, Mori M, Teissier S, Desaintes C (2004) A genomic approach reveals a novel mitotic pathway in papillomavirus carcinogenesis. Cancer Res 64: 895–903.
  • Thorland EC, Myers SL, Persing DH, Sarkar G, McGovern RM, Gostout BS, Smith DI (2000) Human papillomavirus type 16 integrations in cervical tumors frequently occur in common fragile sites. Cancer Res 60: 5916–5921.
  • Thorland EC, Myers SL, Gostout BS, Smith DI (2003) Common fragile sites are preferential targets for HPV16 integrations in cervical tumors. Oncogene 22: 1225–1237.
  • Tonon SA, Picconi MA, Bos PD, Zinovich JB, Galuppo J, Alonio LV, Teyssie AR (2001) Physical status of the E2 human papilloma virus 16 viral gene in cervical preneoplastic and neoplastic lesions. J Clin Virol 21: 129–134.
  • van Driel R, Wansink DG, van Steensel B, Grande MA, Schul W, de Jong L (1995) Nuclear domains and the nuclear matrix. Int Rev Cytol 162A: 151–189.
  • van Holde K, Zlatanova J (1996) What determines the folding of the chromatin fiber? Proc Natl Acad Sci USA 93: 10548–10555.
  • Veress G, Szarka K, Dong XP, Gergely L, Pfister H (1999) Functional significance of sequence variation in the E2 gene and the long control region of human papillomavirus type 16. J Gen Virol 80: 1035–1043.
  • Vernon SD, Unger ER, Miller DL, Lee DR, Reeves WC (1997) Association of human papillomavirus type 16 integration in the E2 gene with poor disease-free survival from cervical cancer. Int J Cancer 74: 50–56.
  • Webster K, Taylor A, Gaston K (2001) Oestrogen and progesterone increase the levels of apoptosis induced by human papillomavirus type 16 E2 and E7 proteins. J Gen Virol 82: 201–213.
  • Wentzensen N, Vinokurova S, von Knebel Doeberitz M (2004) Systematic review of genomic integration sites of human papillomavirus genomes in epithelial dysplasia and invasive cancer of the female lower genital tract. Cancer Res 64: 3878–3884.
  • Yew P, Perricaudet M (1997) Advances in adenoviral vectors: from genetic engineering to their biology. FASEB J 11: 615–623.
  • Yokoyama M, Nakao Y, Iwasaka T, Pater A, Sugimori H (2001) Retinoic acid and interferon-alpha effects on cell growth and differentiation in cervical carcinoma cell lines. Obstet Gynecol 98: 332–340.
  • Yoshinouchi M, Hongo A, Nakamura K, Kodama J, Itoh S, Sakai H, Kudo T (1999) Analysis by multiplex PCR of the physical status of human papillomavirus type 16 DNA in cervical cancers. J Clin Microbiol 37: 3514–3517.
  • Yuan F, Auborn K, James C (1999) Altered growth and viral gene expression in human papillomavirus type 16-containing cancer cell lines treated with progesterone. Cancer Invest 17: 19–29.
  • Zhao W, Chow LT, Broker TR (1997) Transcription activities of human papillomavirus type 11 E6 promoterproximal elements in raft and submerged cultures of foreskin keratinocytes. J Virol 71: 8832–8840.
  • Zou N, Lin BY, Duan F, Lee KY, Jin G, Guan R, Yao G, Lefkowitz EJ, Broker TR, Chow LT (2000) The hinge of the human papillomavirus type 11 E2 protein contains major determinants for nuclear localization and nuclear matrix association. J Virol 74: 3761–3770.
  • zur Hausen H (1996) Papillomavirus infections — a major cause of human cancers. Biochim Biophys Acta 1288: F55–F78.
  • zur Hausen H (2000) Papillomaviruses causing cancer: evasion from host-cell control in early events in carcinogenesis. J Natl Cancer Inst 92: 690–698.

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