Differential effects on apoptosis induction in hepatocyte lines by stable expression of hepatitis B virus X protein

World Journal of Gastroenterology

Volumn 12, Issue 29, 2006, Pages 4673-4682

  Fiedler, Nicola ^a   Quant, Ellen ^b   Fink, Ludger ^a   Sun, Jianguang ^c,d   Schuster, Ralph ^a   Gerlich, Wolfram H ^a   Shaefer, Stephan ^a,c  

^a JUSTUS LIEBIG UNIVERSITY   (Germany)

^b UNIVERSITY OF KIEL   (Germany)

^c UNIVERSITY OF ROSTOCK   (Germany)

^d INSTITUTE OF PLANT PROTECTION   (China)

Author keywords

Apoptosis; Hepatitis B virus; Hepatocyte lines

Indexed keywords

CYCLIN DEPENDENT KINASE INHIBITOR 1; HEPATITIS B VIRUS X PROTEIN; PROTEIN P53;

ANIMAL CELL; APOPTOSIS; ARTICLE; CARCINOGENESIS; CELL CLONING; CELL IMMORTALIZATION; CELL LINE; CELL STRAIN HEPG2; CELL TRANSFORMATION; CELL TYPE; CONTROLLED STUDY; DISEASE ASSOCIATION; ENHANCER REGION; EXPRESSION VECTOR; GENETIC TRANSCRIPTION; GENETIC TRANSFECTION; HEPATITIS B; HEPATITIS B VIRUS; HUMAN; HUMAN CELL; IN VITRO STUDY; INHIBITION KINETICS; LIVER CELL; LIVER CELL CARCINOMA; MALIGNANT TRANSFORMATION; MOUSE; NONHUMAN; NUCLEOTIDE SEQUENCE; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN INDUCTION; TRANSCRIPTION REGULATION; ULTRAVIOLET RADIATION;

EID: 33747629842     PISSN: 10079327     EISSN: None     Source Type: Journal    
DOI: 10.3748/wjg.v12.i29.4673     Document Type: Article

References (111)

1. Brechot C, Jaffredo F, Lagorce D, Gerken G, Meyer zum Buschenfelde K, Papakonstontinou A, Hadziyannis S, Romeo R, Colombo M, Rodes J, Bruix J, Williams R, Naoumov N. Impact of HBV, HCV and GBV-C/HGV on hepatocellular carcinomas in Europe: results of a European concerted action. J Hepatol 1998; 29: 173-183
2. Seifer M, Hohne M, Schaefer S, Gerlich WH. In vitro tumorigenicity of hepatitis B virus DNA and HBx protein. J Hepatol 1991; 13 Suppl 4: S61-65
3. Oguey D, Dumenco LL, Pierce RH, Fausto N. Analysis of the tumorigenicity of the X gene of hepatitis B virus in a nontransformed hepatocyte cell line and the effects of cotransfection with a murine p53 mutant equivalent to human codon 249. Hepatology 1996; 24: 1024-1033
4. Schaefer S, Seifer M, Grimmsmann T, Fink L, Wenderhold S, Hohne MW, Gerlich WH. Properties of tumour suppressor p53 in murine hepatocyte lines transformed by hepatitis B virus X protein. J Gen Virol 1998; 79 ( Pt 4): 767-777
5. Tarn C, Bilodeau ML, Hullinger RL, Andrisani OM. Differential immediate early gene expression in conditional hepatitis B virus pX-transforming versus nontransforming hepatocyte cell lines. J Biol Chem 1999; 274: 2327-2336
6. Shirakata Y, Kawada M, Fujiki Y, Sano H, Oda M, Yaginuma K, Kobayashi M, Koike K. The X gene of hepatitis B virus induced growth stimulation and tumorigenic transformation of mouse NIH3T3 cells. Jpn J Cancer Res 1989; 80: 617-621
7. Seifer M, Höhne M, Schaefer S, Gerlich WH. Malignant transformation of immortalized cells by hepatitis B virus DNA. In: Hollinger F, Lemon S, Margolis H, editors. Viral Hepatitis-1990. New York: Williams and Wilkins, 1991: 586-588
8. Gottlob K, Pagano S, Levrero M, Graessmann A. Hepatitis B virus X protein transcription activation domains are neither required nor sufficient for cell transformation. Cancer Res 1998; 58: 3566-3570
9. Buendia MA, Paterlini P, Tiollais P, Bréchot C. Hepatocellular carcinoma: molecular aspects. In: Zuckerman AJ, Thomas CT, editors. Viral hepatitis. 2nd ed. London: Churchill Livingstone, 1998: 179-200
10. Brechot C, Gozuacik D, Murakami Y, Paterlini-Brechot P. Molecular bases for the development of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Semin Cancer Biol 2000; 10: 211-231
11. Schaefer S. Hepatitis B Virus in Experimental Carcinogenesis. In: Grand RJA, editor. Viruses, cell transformation and cancer. Greenwich: Elsevier, 2001: 193-228
12. Block TM, Mehta AS, Fimmel CJ, Jordan R. Molecular viral oncology of hepatocellular carcinoma. Oncogene 2003; 22: 5093-5107
13. Blum HE, Zhang ZS, Galun E, von Weizsacker F, Garner B, Liang TJ, Wands JR. Hepatitis B virus X protein is not central to the viral life cycle in vitro. J Virol 1992; 66: 1223-1227
14. Bouchard MJ, Puro RJ, Wang L, Schneider RJ. Activation and inhibition of cellular calcium and tyrosine kinase signaling pathways identify targets of the HBx protein involved in hepatitis B virus replication. J Virol 2003; 77: 7713-7719
15. Hafner A, Brandenburg B, Hildt E. Reconstitution of gene expression from a regulatory-protein-deficient hepatitis B virus genome by cell-permeable HBx protein. EMBO Rep 2003; 4: 767-773
16. Zhang Z, Protzer U, Hu Z, Jacob J, Liang TJ. Inhibition of cellular proteasome activities enhances hepadnavirus replication in an HBX-dependent manner. J Virol 2004; 78: 4566-4572
17. Burrell CJ, Chisari FV, Gerlich WH, Gowans EJ, Howard CR, Kann M. Hepadnaviridae. In: van Regenmortel MHV, Fauquet CM, Bishop DHL, editors. Virus Taxonomy. Seventh Report of the International Committee on Taxonomy of Viruses. San Diego: Academic Press, 2000: 325-334
18. Chen HS, Kaneko S, Girones R, Anderson RW, Hornbuckle WE, Tennant BC, Cote PJ, Gerin JL, Purcell RH, Miller RH. The woodchuck hepatitis virus X gene is important for establishment of virus infection in woodchucks. J Virol 1993; 67: 1218-1226
19. Zoulim F, Saputelli J, Seeger C. Woodchuck hepatitis virus X protein is required for viral infection in vivo. J Virol 1994; 68: 2026-2030
20. Yen TS. Hepadnaviral X Protein:Review of Recent Progress. J Biomed Sci 1996; 3: 20-30
21. Madden CR, Slagle BL. Stimulation of cellular proliferation by hepatitis B virus X protein. Dis Markers 2001; 17: 153-157
22. Murakami S. Hepatitis B virus X protein: a multifunctional viral regulator. J Gastroenterol 2001; 36: 651-660
23. Waris G, Siddiqui A. Regulatory mechanisms of viral hepatitis B and C. J Biosci 2003; 28: 311-321
24. Kanzler S, Galle PR. Apoptosis and the liver. Semin Cancer Biol 2000; 10: 173-184
25. Avantaggiati ML, Natoli G, Balsano C, Chirillo P, Artini M, De Marzio E, Collepardo D, Levrero M. The hepatitis B virus (HBV) pX transactivates the c-fos promoter through multiple cis-acting elements. Oncogene 1993; 8: 1567-1574
26. Kekule AS, Lauer U, Weiss L, Luber B, Hofschneider PH. Hepatitis B virus transactivator HBx uses a tumour promoter signalling pathway. Nature 1993; 361: 742-745
27. Twu JS, Lai MY, Chen DS, Robinson WS. Activation of protooncogene c-jun by the X protein of hepatitis B virus. Virology 1993; 192: 346-350
28. Koike K, Moriya K, Yotsuyanagi H, Iino S, Kurokawa K. Induction of cell cycle progression by hepatitis B virus HBx gene expression in quiescent mouse fibroblasts. J Clin Invest 1994; 94: 44-49
29. Benn J, Schneider RJ. Hepatitis B virus HBx protein deregulates cell cycle checkpoint controls. Proc Natl Acad Sci USA 1995; 92: 11215-11219
30. Roulston A, Marcellus RC, Branton PE. Viruses and apoptosis. Annu Rev Microbiol 1999; 53: 577-628
31. Butel JS. Viral carcinogenesis: revelation of molecular mechanisms and etiology of human disease. Carcinogenesis 2000; 21: 405-426
32. Lowe SW, Lin AW. Apoptosis in cancer. Carcinogenesis 2000; 21: 485-495
33. Schuster R, Gerlich WH, Schaefer S. Induction of apoptosis by the transactivating domains of the hepatitis B virus X gene leads to suppression of oncogenic transformation of primary rat embryo fibroblasts. Oncogene 2000; 19: 1173-1180
34. Su F, Schneider RJ. Hepatitis B virus HBx protein sensitizes cells to apoptotic killing by tumor necrosis factor alpha. Proc Natl Acad Sci USA 1997; 94: 8744-8749
35. Chirillo P, Pagano S, Natoli G, Puri PL, Burgio VL, Balsano C, Levrero M. The hepatitis B virus X gene induces p53-mediated programmed cell death. Proc Natl Acad Sci USA 1997; 94: 8162-8167
36. Kim H, Lee H, Yun Y. X-gene product of hepatitis B virus induces apoptosis in liver cells. J Biol Chem 1998; 273: 381-385
37. Terradillos O, Pollicino T, Lecoeur H, Tripodi M, Gougeon ML, Tiollais P, Buendia MA. p53-independent apoptotic effects of the hepatitis B virus HBx protein in vivo and in vitro. Oncogene 1998; 17: 2115-2123
38. Bergametti F, Prigent S, Luber B, Benoit A, Tiollais P, Sarasin A, Transy C. The proapoptotic effect of hepatitis B virus HBx protein correlates with its transactivation activity in stably transfected cell lines. Oncogene 1999; 18: 2860-2871
39. Shintani Y, Yotsuyanagi H, Moriya K, Fujie H, Tsutsumi T, Kanegae Y, Kimura S, Saito I, Koike K. Induction of apoptosis after switch-on of the hepatitis B virus X gene mediated by the Cre/loxP recombination system. J Gen Virol 1999; 80 ( Pt 12): 3257-3265
40. Chang SF, Netter HJ, Hildt E, Schuster R, Schaefer S, Hsu YC, Rang A, Will H. Duck hepatitis B virus expresses a regulatory HBx-like protein from a hidden open reading frame. J Virol 2001; 75: 161-170
41. Schuster R, Hildt E, Chang SF, Terradillos O, Pollicino T, Lanford R, Gerlich WH, Will H, Schaefer S. Conserved transactivating and pro-apoptotic functions of hepadnaviral X protein in ortho- and avihepadnaviruses. Oncogene 2002; 21: 6606-6613
42. Song CZ, Bai ZL, Song CC, Wang QW. Aggregate formation of hepatitis B virus X protein affects cell cycle and apoptosis. World J Gastroenterol 2003; 9: 1521-1524
43. Su F, Theodosis CN, Schneider RJ. Role of NF-kappaB and myc proteins in apoptosis induced by hepatitis B virus HBx protein. J Virol 2001; 75: 215-225
44. Chami M, Ferrari D, Nicotera P, Paterlini-Brechot P, Rizzuto R. Caspase-dependent alterations of Ca2+ signaling in the induction of apoptosis by hepatitis B virus X protein. J Biol Chem 2003; 278: 31745-31755
45. Kim KH, Seong BL. Pro-apoptotic function of HBV X protein is mediated by interaction with c-FLIP and enhancement of death-inducing signal. EMBO J 2003; 22: 2104-2116
46. Shirakata Y, Koike K. Hepatitis B virus X protein induces cell death by causing loss of mitochondrial membrane potential. J Biol Chem 2003; 278: 22071-22078
47. Chen HY, Tang NH, Li XJ, Zhang SJ, Chen ZX, Wang XZ. Transfection and expression of hepatitis B virus x gene and its effect on apoptosis in HL-7702 cells. World J Gastroenterol 2004; 10: 959-964
48. Tanaka Y, Kanai F, Kawakami T, Tateishi K, Ijichi H, Kawabe T, Arakawa Y, Kawakami T, Nishimura T, Shirakata Y, Koike K, Omata M. Interaction of the hepatitis B virus X protein (HBx) with heat shock protein 60 enhances HBx-mediated apoptosis. Biochem Biophys Res Commun 2004; 318: 461-469
49. Wang XW, Gibson MK, Vermeulen W, Yeh H, Forrester K, Sturzbecher HW, Hoeijmakers JH, Harris CC. Abrogation of p53-induced apoptosis by the hepatitis B virus X gene. Cancer Res 1995; 55: 6012-6016
50. Elmore LW, Hancock AR, Chang SF, Wang XW, Chang S, Callahan CP, Geller DA, Will H, Harris CC. Hepatitis B virus X protein and p53 tumor suppressor interactions in the modulation of apoptosis. Proc Natl Acad Sci USA 1997; 94: 14707-14712
51. Gottlob K, Fulco M, Levrero M, Graessmann A. The hepatitis B virus HBx protein inhibits caspase 3 activity. J Biol Chem 1998; 273: 33347-33353
52. Diao J, Khine AA, Sarangi F, Hsu E, Iorio C, Tibbles LA, Woodgett JR, Penninger J, Richardson CD. X protein of hepatitis B virus inhibits Fas-mediated apoptosis and is associated with up-regulation of the SAPK/ JNK pathway. J Biol Chem 2001; 276: 8328-8340
53. Shih WL, Kuo ML, Chuang SE, Cheng AL, Doong SL. Hepatitis B virus X protein inhibits transforming growth factor-beta -induced apoptosis through the activation of phosphatidylinositol 3-kinase pathway. J Biol Chem 2000; 275: 25858-25864
54. Huo TI, Wang XW, Forgues M, Wu CG, Spillare EA, Giannini C, Brechot C, Harris CC. Hepatitis B virus X mutants derived from human hepatocellular carcinoma retain the ability to abrogate p53-induced apoptosis. Oncogene 2001; 20: 3620-3628
55. Kim YC, Song KS, Yoon G, Nam MJ, Ryu WS. Activated ras oncogene collaborates with HBx gene of hepatitis B virus to transform cells by suppressing HBx-mediated apoptosis. Oncogene 2001; 20: 16-23
56. Lee YI, Kang-Park S, Do SI, Lee YI. The hepatitis B virus-X protein activates a phosphatidylinositol 3-kinase-dependent survival signaling cascade. J Biol Chem 2001; 276: 16969-16977
57. Li D, Chen X, Zhang W. The inhibition of apoptosis of hepatoma cells induced by HBx is mediated by up-regulation of survivin expression. J Huazhong Univ Sci Technolog Med Sci 2003; 23: 383-386
58. Shih WL, Kuo ML, Chuang SE, Cheng AL, Doong SL. Hepatitis B virus X protein activates a survival signaling by linking SRC to phosphatidylinositol 3-kinase. J Biol Chem 2003; 278: 31807-31813
59. Kalra N, Kumar V. c-Fos is a mediator of the c-myc-induced apoptotic signaling in serum-deprived hepatoma cells via the p38 mitogen-activated protein kinase pathway. J Biol Chem 2004; 279: 25313-25319
60. Rich T, Allen RL, Wyllie AH. Defying death after DNA damage. Nature 2000; 407: 777-783
61. Slee EA, O'Connor DJ, Lu X. To die or not to die: how does p53 decide? Oncogene 2004; 23: 2809-2818
62. Wang XW, Forrester K, Yeh H, Feitelson MA, Gu JR, Harris CC. Hepatitis B virus X protein inhibits p53 sequence-specific DNA binding, transcriptional activity, and association with transcription factor ERCC3. Proc Natl Acad Sci USA 1994; 91: 2230-2234
63. Truant R, Antunovic J, Greenblatt J, Prives C, Cromlish JA. Direct interaction of the hepatitis B virus HBx protein with p53 leads to inhibition by HBx of p53 response element-directed transactivation. J Virol 1995; 69: 1851-1859
64. Ueda H, Ullrich SJ, Gangemi JD, Kappel CA, Ngo L, Feitelson MA, Jay G. Functional inactivation but not structural mutation of p53 causes liver cancer. Nat Genet 1995; 9: 41-47
65. Takada S, Kaneniwa N, Tsuchida N, Koike K. Cytoplasmic retention of the p53 tumor suppressor gene product is observed in the hepatitis B virus X gene-transfected cells. Oncogene 1997; 15: 1895-1901
66. Prost S, Ford JM, Taylor C, Doig J, Harrison DJ. Hepatitis B x protein inhibits p53-dependent DNA repair in primary mouse hepatocytes. J Biol Chem 1998; 273: 33327-33332
67. Groisman IJ, Koshy R, Henkler F, Groopman JD, Alaoui-Jamali MA. Downregulation of DNA excision repair by the hepatitis B virus-x protein occurs in p53-proficient and p53-deficient cells. Carcinogenesis 1999; 20: 479-483
68. Jia L, Wang XW, Harris CC. Hepatitis B virus X protein inhibits nucleotide excision repair. Int J Cancer 1999; 80: 875-879
69. Sohn S, Jaitovitch-Groisman I, Benlimame N, Galipeau J, Batist G, Alaoui-Jamali MA. Retroviral expression of the hepatitis B virus x gene promotes liver cell susceptibility to carcinogen-induced site specific mutagenesis. Mutat Res 2000; 460: 17-28
70. Jaitovich-Groisman I, Benlimame N, Slagle BL, Perez MH, Alpert L, Song DJ, Fotouhi-Ardakani N, Galipeau J, Alaoui-Jamali MA. Transcriptional regulation of the TFIIH transcription repair components XPB and XPD by the hepatitis B virus x protein in liver cells and transgenic liver tissue. J Biol Chem 2001; 276: 14124-14132
71. Takada S, Kaneniwa N, Tsuchida N, Koike K. Hepatitis B virus X gene expression is activated by X protein but repressed by p53 tumor suppressor gene product in the transient expression system. Virology 1996; 216: 80-89
72. Doitsh G, Shaul Y. HBV transcription repression in response to genotoxic stress is p53-dependent and abrogated by pX. Oncogene 1999; 18: 7506-7513
73. Ogden SK, Lee KC, Barton MC. Hepatitis B viral transactivator HBx alleviates p53-mediated repression of alpha-fetoprotein gene expression. J Biol Chem 2000; 275: 27806-27814
74. Uchida T, Takahashi K, Tatsuno K, Dhingra U, Eliason JF. Inhibition of hepatitis-B-virus core promoter by p53: implications for carcinogenesis in hepatocytes. Int J Cancer 1996; 67: 892-897
75. Dandri M, Schirmacher P, Rogler CE. Woodchuck hepatitis virus X protein is present in chronically infected woodchuck liver and woodchuck hepatocellular carcinomas which are permissive for viral replication. J Virol 1996; 70: 5246-5254
76. Dandri M, Petersen J, Stockert RJ, Harris TM, Rogler CE. Metabolic labeling of woodchuck hepatitis B virus X protein in naturally infected hepatocytes reveals a bimodal half-life and association with the nuclear framework. J Virol 1998; 72: 9359-9364
77. Su Q, Schroder CH, Hofmann WJ, Otto G, Pichlmayr R, Bannasch P. Expression of hepatitis B virus X protein in HBV-infected human livers and hepatocellular carcinomas. Hepatology 1998; 27: 1109-1120
78. Wu JC, Merlino G, Fausto N. Establishment and characterization of differentiated, nontransformed hepatocyte cell lines derived from mice transgenic for transforming growth factor alpha. Proc Natl Acad Sci USA 1994; 91: 674-678
79. Aden DP, Fogel A, Plotkin S, Damjanov I, Knowles BB. Controlled synthesis of HBsAg in a differentiated human liver carcinoma-derived cell line. Nature 1979; 282: 615-616
80. Noda A, Ning Y, Venable SF, Pereira-Smith OM, Smith JR. Cloning of senescent cell-derived inhibitors of DNA synthesis using an expression screen. Exp Cell Res 1994; 211: 90-98
81. Luckow B, Schutz G. CAT constructions with multiple unique restriction sites for the functional analysis of eukaryotic promoters and regulatory elements. Nucleic Acids Res 1987; 15: 5490
82. Kern SE, Pietenpol JA, Thiagalingam S, Seymour A, Kinzler KW, Vogelstein B. Oncogenic forms of p53 inhibit p53-regulated gene expression. Science 1992; 256: 827-830
83. Hall PA, Lane DP. Tumor suppressors: a developing role for p53? Curr Biol 1997; 7: R144-147
84. Puisieux A, Ji J, Guillot C, Legros Y, Soussi T, Isselbacher K, Ozturk M. p53-mediated cellular response to DNA damage in cells with replicative hepatitis B virus. Proc Natl Acad Sci USA 1995; 92: 1342-1346
85. Lu X, Lane DP. Differential induction of transcriptionally active p53 following UV or ionizing radiation: defects in chromosome instability syndromes? Cell 1993; 75: 765-778
86. Poon RY, Jiang W, Toyoshima H, Hunter T. Cyclin-dependent kinases are inactivated by a combination of p21 and Thr-14/Tyr-15 phosphorylation after UV-induced DNA damage. J Biol Chem 1996; 271: 13283-13291
87. Petrocelli T, Poon R, Drucker DJ, Slingerland JM, Rosen CF. UVB radiation induces p21Cip1/WAF1 and mediates G1 and S phase checkpoints. Oncogene 1996; 12: 1387-1396
88. May P, May E. Twenty years of p53 research: structural and functional aspects of the p53 protein. Oncogene 1999; 18: 7621-7636
89. Lakin ND, Jackson SP, Regulation of p53 in response to DNA damage. Oncogene 1999; 18: 7644-7655
90. el-Deiry WS, Tokino T, Velculescu VE, Levy DB, Parsons R, Trent JM, Lin D, Mercer WE, Kinzler KW, Vogelstein B. WAF1, a potential mediator of p53 tumor suppression. Cell 1993; 75: 817-825
91. Lu X, Burbidge SA, Griffin S, Smith HM. Discordance between accumulated p53 protein level and its transcriptional activity in response to u.v. radiation. Oncogene 1996; 13: 413-418
92. Albrecht JH, Meyer AH, Hu MY. Regulation of cyclin-dependent kinase inhibitor p21(WAF1/Cip1/Sdi1) gene expression in hepatic regeneration. Hepatology 1997; 25: 557-563
93. Lane DP. Cancer. p53, guardian of the genome. Nature 1992; 358: 15-16
94. Lowe SW, Ruley HE. Stabilization of the p53 tumor suppressor is induced by adenovirus 5 E1A and accompanies apoptosis. Genes Dev 1993; 7: 535-545
95. Scheffner M, Huibregtse JM, Vierstra RD, Howley PM. The HPV-16 E6 and E6-AP complex functions as a ubiquitin-protein ligase in the ubiquitination of p53. Cell 1993; 75: 495-505
96. Park US, Park SK, Lee YI, Park JG, Lee YI. Hepatitis B virus-X protein upregulates the expression of p21waf1/cip1 and prolongs G1→S transition via a p53-independent pathway in human hepatoma cells. Oncogene 2000; 19: 3384-3394
97. Chen X, Ko LJ, Jayaraman L, Prives C. p53 levels, functional domains, and DNA damage determine the extent of the apoptotic response of tumor cells. Genes Dev 1996; 10: 2438-2451
98. Han J, Yoo HY, Choi BH, Rho HM. Selective transcriptional regulations in the human liver cell by hepatitis B viral X protein. Biochem Biophys Res Commun 2000; 272: 525-530
99. Livezey KW, Negorev D, Simon D. Hepatitis B virus-transfected Hep G2 cells demonstrate genetic alterations and de novo viral integration in cells replicating HBV. Mutat Res 2000; 452: 163-178
100. Kobayashi S, Matsushita K, Saigo K, Urashima T, Asano T, Hayashi H, Ochiai T. P21WAF1/CIP1 messenger RNA expression in hepatitis B, C virus-infected human hepatocellular carcinoma tissues. Cancer 2001; 91: 2096-2103
101. Wu CG, Salvay DM, Forgues M, Valerie K, Farnsworth J, Markin RS, Wang XW. Distinctive gene expression profiles associated with Hepatitis B virus x protein. Oncogene 2001; 20: 3674-3682
102. Haviv I, Vaizel D, Shaul Y. The X protein of hepatitis B virus coactivates potent activation domains. Mol Cell Biol 1995; 15: 1079-1085
103. Akagi T, Ono H, Shimotohno K. Expression of cell-cycle regulatory genes in HTLV-I infected T-cell lines: possible involvement of Tax1 in the altered expression of cyclin D2, p18Ink4 and p21Waf1/Cip1/Sdi1. Oncogene 1996; 12: 1645-1652
104. Cereseto A, Diella F, Mulloy JC, Cara A, Michieli P, Grassmann R, Franchini G, Klotman ME. p53 functional impairment and high p21waf1/cip1 expression in human T-cell lymphotropic/leukemia virus type I-transformed T cells. Blood 1996; 88: 1551-1560
105. Mesnard JM, Devaux C. Multiple control levels of cell proliferation by human T-cell leukemia virus type 1 Tax protein. Virology 1999; 257: 277-284
106. Faktor O, Shaul Y. The identification of hepatitis B virus X gene responsive elements reveals functional similarity of X and HTLV-I tax. Oncogene 1990; 5: 867-872
107. Morozov A, Shiyanov P, Barr E, Leiden JM, Raychaudhuri P. Accumulation of human papillomavirus type 16 E7 protein bypasses G1 arrest induced by serum deprivation and by the cell cycle inhibitor p21. J Virol 1997; 71: 3451-3457
108. Ruesch MN, Laimins LA. Initiation of DNA synthesis by human papillomavirus E7 oncoproteins is resistant to p21-mediated inhibition of cyclin E-cdk2 activity. J Virol 1997; 71: 5570-5578
109. Butz K, Geisen C, Ullmann A, Zentgraf H, Hoppe-Seyler F. Uncoupling of p21WAF1/CIP1/SDI1 mRNA and protein expression upon genotoxic stress. Oncogene 1998; 17: 781-787
110. Fiedler N. Kombinierter Effekt des Hepatitis B Virus X Proteins und des Tumorsuppressorproteins p53 auf virale und zelluläre Promotoren [Diplomarbeit]. Gießen: Justus-Liebig-Universität, 1996
111. Tarn C, Lee S, Hu Y, Ashendel C, Andrisani OM. Hepatitis B virus X protein differentially activates RAS-RAF-MAPK and JNK pathways in X-transforming versus non-transforming AML12 hepatocytes. J Biol Chem 2001; 276: 34671-34680