Regulation of telomerase and telomeres: Human tumor viruses take control

Journal of the National Cancer Institute

Volumn 100, Issue 2, 2008, Pages 98-108

  Bellon, Marcia ^a   Nicot, Christophe ^a  

^a UNIVERSITY OF KANSAS SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ONCOPROTEIN; TELOMERASE; TELOMERASE REVERSE TRANSCRIPTASE; VIRUS PROTEIN; TERT PROTEIN, HUMAN; UNCLASSIFIED DRUG;

CARCINOGENESIS; CELL TRANSFORMATION; DNA TUMOR VIRUS; ENZYME ACTIVITY; ENZYME REGULATION; EPIGENETICS; EPSTEIN BARR VIRUS; HEPATITIS B VIRUS; HEPATITIS C VIRUS; HUMAN HERPESVIRUS 8; HUMAN T CELL LEUKEMIA VIRUS 1; PRIORITY JOURNAL; REVIEW; RNA TUMOR VIRUS; SARCOMA; TELOMERE; TUMOR VIRUS; VIRUS INFECTION; WART VIRUS; CELL AGING; CELL DIVISION; CELL PROLIFERATION; DNA VIRUS; ENZYMOLOGY; GENE EXPRESSION REGULATION; GENETIC TRANSCRIPTION; GENETICS; HUMAN; METABOLISM; NEOPLASM; PAPILLOMA VIRUS; RETROVIRUS; RNA VIRUS; VIROLOGY;

CELL AGING; CELL DIVISION; CELL PROLIFERATION; CELL TRANSFORMATION, NEOPLASTIC; DELTARETROVIRUS; DNA VIRUSES; GENE EXPRESSION REGULATION, ENZYMOLOGIC; GENE EXPRESSION REGULATION, NEOPLASTIC; HEPACIVIRUS; HEPATITIS B VIRUS; HERPESVIRUS 4, HUMAN; HERPESVIRUS 8, HUMAN; HUMANS; NEOPLASMS; ONCOGENE PROTEINS; PAPILLOMAVIRIDAE; RNA VIRUSES; TELOMERASE; TELOMERE; TRANSCRIPTION, GENETIC; TUMOR VIRUS INFECTIONS; VIRAL PROTEINS;

EID: 38449104105     PISSN: 00278874     EISSN: 14602105     Source Type: Journal    
DOI: 10.1093/jnci/djm269     Document Type: Review

References (128)

1. Cong YS, Wright WE, Shay JW. Human telomerase and its regulation. Microbiol Mol Biol Rev. 2002;66:407-425.
2. de Lange T. Telomere-related genome instability in cancer. Cold Spring Harb Symp Quant Biol. 2005;70:197-204.
3. Meyerson M, Counter CM, Eaton EN, et al. hEST2, the putative human telomerase catalytic subunit gene, is up-regulated in tumor cells and during immortalization. Cell. 1997;90:785-795.
4. Nakamura TM, Morin GB, Chapman KB, et al. Telomerase catalytic subunit homologs from fission yeast and human. Science. 1997;277:955-959.
5. Herbert B, Pitts AE, Baker SI, et al. Inhibition of human telomerase in immortal human cells leads to progressive telomere shortening and cell death. Proc Natl Acad Sci USA. 1999;96:14276-14281.
6. Bryan TM, Englezou A, Dalla-Pozza L, Dunham MA, Reddel RR. Evidence for an alternative mechanism for maintaining telomere length in human tumors and tumor-derived cell lines. Nat Med. 1997;3:1271-1274.
7. Wang RC, Smogorzewska A, de Lange T. Homologous recombination generates T-loop-sized deletions at human telomeres. Cell. 2004;119:355-368.
8. Dunham MA, Neumann AA, Fasching CL, Reddel RR. Telomere maintenance by recombination in human cells. Nat Genet. 2000;26:447-450.
9. Chen LY, Liu D, Songyang Z. Telomere maintenance through spatial control of telomeric proteins. Mol Cell Biol. 2007;27:5898-5909.
10. de Lange T. Shelterin:the protein complex that shapes and safeguards human telomeres. Genes Dev. 2005;19:2100-2110.
11. Jiang XR, Jimenez G, Chang E, et al. Telomerase expression in human somatic cells does not induce changes associated with a transformed phenotype . Nat Genet. 1999;21:111-114.
12. Hahn WC, Counter CM, Lundberg AS, Beijersbergen RL, Brooks MW, Weinberg RA. Creation of human tumour cells with defined genetic elements. Nature. 1999;400:464-468.
13. Kendall SD, Linardic CM, Adam SJ, Counter CM. A network of genetic events sufficient to convert normal human cells to a tumorigenic state. Cancer Res. 2005;65:9824-9828.
14. Young LS, Murray PG. Epstein-Barr virus and oncogenesis: from latent genes to tumours. Oncogene. 2003;22:5108-5121.
15. Kerekhanjanarong V, Sitawarin S, Sakdikul S, et al. Telomerase assay and nested polymerase chain reaction from nasopharyngeal swabs for early noninvasive detection of nasopharyngeal carcinoma. Otolaryngol Head Neck Surg. 2000;123:624-629.
16. Kataoka H, Tahara H, Watanabe T, et al. Immortalization of immunologically committed Epstein-Barr virus-transformed human B-lymphoblastoid cell lines accompanied by a strong telomerase activity. Differentiation. 1997;62:203-211.
17. Zheng H, Li LL, Hu DS, Deng XY, Cao Y. Role of Epstein-Barr virus encoded latent membrane protein 1 in the carcinogenesis of nasopharyngeal carcinoma. Cell Mol Immunol. 2007;4:185-196.
18. Yang J, Deng X, Deng L, Gu H, Fan W, Cao Y. Telomerase activation by Epstein-Barr virus latent membrane protein 1 is associated with c-Myc expression in human nasopharyngeal epithelial cells. J Exp Clin Cancer Res. 2004;23:495-506.
19. Mei YP, Zhu XF, Zhou JM, Huang H, Deng R, Zeng YX. siRNA targeting LMP1-induced apoptosis in EBV-positive lymphoma cells is associated with inhibition of telomerase activity and expression. Cancer Lett. 2006;232:189-198.
20. Terrin L, Dolcetti R, Corradini I, et al. hTERT inhibits the Epstein-Barr virus lytic cycle and promotes the proliferation of primary B lymphocytes: implications for EBV-driven lymphomagenesis. Int J Cancer. 2007;121:576-587.
21. Sugimoto M, Tahara H, Ide T, Furuichi Y. Steps involved in immortalization and tumorigenesis in human B-lymphoblastoid cell lines transformed by Epstein-Barr virus. Cancer Res. 2004;64:3361-3364.
22. Okubo M, Tsurukubo Y, Higaki T, et al. Clonal chromosomal aberrations accompanied by strong telomerase activity in immortalization of human B-lymphoblastoid cell lines transformed by Epstein-Barr virus. Cancer Genet Cytogenet. 2001;129:30-34.
23. Young LS, Rickinson AB. Epstein-Barr virus: 40 years on. Nat Rev Cancer. 2004;4:757-768.
24. Chen F, Liu C, Lindvall C, Xu D, Ernberg I. Epstein-Barr virus latent membrane 2A (LMP2A) down-regulates telomerase reverse transcriptase (hTERT) in epithelial cell lines. Int J Cancer. 2005;113:284-289.
25. Mochida A, Gotoh E, Senpuku H, et al. Telomere size and telomerase activity in Epstein-Barr virus (EBV)-positive and EBV-negative Burkitt's lymphoma cell lines. Arch Virol. 2005;150:2139-2150.
26. Kamranvar SA, Gruhne B, Szeles A, Masucci MG. Epstein-Barr virus promotes genomic instability in Burkitt's lymphoma. Oncogene. 2007;26:5115-5123.
27. Schulz TF. The pleiotropic effects of Kaposi's sarcoma herpesvirus. J Pathol. 2006;208:187-198.
28. Flore O, Rafii S, Ely S, O'Leary JJ, Hyjek EM, Cesarman E. Transformation of primary human endothelial cells by Kaposi's sarcoma-associated herpesvirus. Nature. 1998;394:588-592.
29. Ballestas ME, Chatis PA, Kaye KM. Efficient persistence of extrachromosomal KSHV DNA mediated by latency-associated nuclear antigen. Science. 1999;284:641-644
30. Hu J, Garber AC, Renne R. The latency-associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus supports latent DNA replication in dividing cells. J Virol. 2002;76:11677-11687.
31. Knight JS, Cotter MA, Robertson ES. The latency-associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus transactivates the telomerase reverse transcriptase promoter. J Biol Chem. 276:22971-22978.
32. Verma SC, Borah S, Robertson ES. Latency-associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus up-regulates transcription of human telomerase reverse transcriptase promoter through interaction with transcription factor Sp1. J Virol. 2004;78:10348-10359.
33. Bais C, Van Geelen A, Eroles P, et al. Kaposi's sarcoma associated herpes-virus G protein-coupled receptor immortalizes human endothelial cells by activation of the VEGF receptor-2/KDR. Cancer Cell. 2003;3:131-143.
34. Dunne EF, Markowitz LE. Genital human papillomavirus infection. Clin Infect Dis. 2006;43:624-629.
35. Ferenczy A, Franco E. Persistent human papillomavirus infection and cervical neoplasia. Lancet Oncol. 2002;3:11-16.
36. Schiller JT, Lowy DR. Prospects for cervical cancer prevention by human papillomavirus vaccination. Cancer Res. 2006;66:10229-10232.
37. Klingelhutz AJ, Foster SA, McDougall JK. Telomerase activation by the E6 gene product of human papillomavirus type 16. Nature. 1996;380:79-82.
38. zur HH. Papillomaviruses and cancer:from basic studies to clinical application. Nat Rev Cancer. 2002;2:342-350.
39. Gewin L, Myers H, Kiyono T, Galloway DA. Identification of a novel telomerase repressor that interacts with the human papillomavirus type-16 E6/E6-AP complex. Genes Dev. 2004;18:2269-2282.
40. Sekaric P, Cherry JJ, Androphy EJ. Binding of HPV 16 E6 to E6AP is not required for activation of hTERT. J Virol. 2008;82:71-76.
41. Filatov L, Golubovskaya V, Hurt JC, Byrd LL, Phillips JM, Kaufmann WK. Chromosomal instability is correlated with telomere erosion and inactivation of G2 checkpoint function in human fibroblasts expressing human papillomavirus type 16 E6 oncoprotein. Oncogene. 1998;16:1825-1838.
42. Zhang A, Wang J, Zheng B, et al. Telomere attrition predominantly occurs in precursor lesions during in vivo carcinogenic process of the uterine cervix. Oncogene. 2004;23:7441-7447.
43. Hegde RS. The papillomavirus E2 proteins:structure, function, and biology. Annu Rev Biophys Biomol Struct. 2002;31:343-360.
44. Cripe TP, Haugen TH, Turk JP, et al. Transcriptional regulation of the human papillomavirus-16 E6-E7 promoter by a keratinocyte-dependent enhancer, and by viral E2 trans-activator and repressor gene products: implications for cervical carcinogenesis. EMBO J. 1987;6:3745-3753.
45. Block TM, Mehta AS, Fimmel CJ, Jordan R. Molecular viral oncology of hepatocellular carcinoma. Oncogene. 2003;22:5093-5107.
46. Tahara H, Nakanishi T, Kitamoto M, et al. Telomerase activity in human liver tissues: comparison between chronic liver disease and hepatocellular carcinomas. Cancer Res. 1995;55:2734-2736.
47. Miura N, Horikawa I, Nishimoto A, et al. Progressive telomere shortening and telomerase reactivation during hepatocellular carcinogenesis. Cancer Genet Cytogenet. 1997;93:56-62.
48. Ohashi K, Tsutsumi M, Nakajima Y, Kobitsu K, Nakano H, Konishi Y. Telomere changes in human hepatocellular carcinomas and hepatitis virus infected noncancerous livers. Cancer. 1996;77:1747-1751.
49. Yokota T, Suda T, Igarashi M, et al. Telomere length variation and maintenance in hepatocarcinogenesis. Cancer. 2003;98:110-118.
50. Kekule AS, Lauer U, Meyer M, Caselmann WH, Hofschneider PH, Koshy R. The preS2/S region of integrated hepatitis B virus DNA encodes a transcriptional transactivator. Nature. 1990;343:457-461.
51. 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.
52. Zhang X, Dong N, Zhang H, You J, Wang H, Ye L. Effects of hepatitis B virus X protein on human telomerase reverse transcriptase expression and activity in hepatoma cells. J Lab Clin Med. 2005;145:98-104.
53. Liu H, Luan F, Ju Y, et al. In vitro transfection of the hepatitis B virus PreS2 gene into the human hepatocarcinoma cell line HepG2 induces upregulation of human telomerase reverse transcriptase. Biochem Biophys Res Commun. 2007;355:379-384.
54. Franchini G, Nicot C, Johnson JM. Seizing of T cells by human T-cell leukemia/lymphoma virus type 1. Adv Cancer Res. 2003;89:69-132.
55. Bellon M, Datta A, Brown M, et al. Increased expression of telomere length regulating factors TRF1, TRF2 and TIN2 in patients with adult T-cell leukemia. Int J Cancer. 2006;119:2090-2097.
56. Kubuki Y, Suzuki M, Sasaki H, et al. Telomerase activity and telomere length as prognostic factors of adult T-cell leukemia. Leuk Lymphoma. 2005;46:393-399.
57. Uchida N, Otsuka T, Arima F, et al. Correlation of telomerase activity with development and progression of adult T-cell leukemia. Leuk Res. 1999;23:311-316.
58. Franzese O, Balestrieri E, Comandini A, Forte G, Macchi B, Bonmassar E. Telomerase activity of human peripheral blood mononuclear cells in the course of HTLV type 1 infection in vitro. AIDS Res Hum Retroviruses. 2002;18:249-251.
59. Datta A, Bellon M, Sinha-Datta U, et al. Persistent inhibition of telomerase reprograms adult T-cell leukemia to p53-dependent senescence. Blood. 2006;108:1021-1029.
60. Sinha-Datta U, Horikawa I, Michishita E, et al. Transcriptional activation of hTERT through the NF-kappaB pathway in HTLV-1-transformed cells. Blood. 2004;104:2523-2531.
61. Gabet AS, Mortreux F, Charneau P, et al. Inactivation of hTERT transcription by Tax. Oncogene. 2003;22:3734-3741.
62. Bellon M, Nicot C. Telomerase:a crucial player in HTLV-1-induced human T-cell leukemia. Cancer Genomics Proteomics. 2007;4:21-25.
63. Deville L, Hillion J, Lanotte M, Rousselot P, Segal-Bendirdjian E. Diagnostics, prognostic and therapeutic exploitation of telomeres and telomerase in leukemias. Curr Pharm Biotechnol. 2006;3:171-183.
64. Brummendorf TH, Holyoake TL, Rufer N, et al. Prognostic implications of differences in telomere length between normal and malignant cells from patients with chronic myeloid leukemia measured by flow cytometry. Blood. 2000;95:1883-1890.
65. Grabowski P, Hultdin M, Karlsson K, et al. Telomere length as a prognostic parameter in chronic lymphocytic leukemia with special reference to VH gene mutation status. Blood. 2005;105:4807-4812.
66. Bisoffi M, Heaphy CM, Griffith JK. Telomeres: prognostic markers for solid tumors. Int J Cancer. 2006;119:2255-2260.
67. Zhang DK, Ngan HY, Cheng RY, Cheung AN, Liu SS, Tsao SW. Clinical significance of telomerase activation and telomeric restriction fragment (TRF) in cervical cancer. Eur J Cancer. 1999;35:154-160.
68. Ducrest AL, Amacker M, Mathieu YD, et al. Regulation of human telomerase activity: repression by normal chromosome 3 abolishes nuclear telomerase reverse transcriptase transcripts but does not affect c-Myc activity. Cancer Res. 2001;61:7594-7602.
69. Horikawa I, Cable PL, Afshari C, Barrett JC. Cloning and characterization of the promoter region of human telomerase reverse transcriptase gene. Cancer Res. 1999;59:826-830.
70. Wang J, Xie LY, Allan S, Beach D, Hannon GJ. Myc activates telomerase. Genes Dev. 1998;12:1769-1774.
71. Wu KJ, Grandori C, Amacker M, et al. Direct activation of TERT transcription by c-MYC. Nat Genet. 1999;21:220-224.
72. Kyo S, Takakura M, Taira T, et al. Sp1 cooperates with c-Myc to activate transcription of the human telomerase reverse transcriptase gene (hTERT). Nucleic Acids Res. 2000;28:669-677.
73. Oh ST, Kyo S, Laimins LA. Telomerase activation by human papillomavirus type 16 E6 protein: induction of human telomerase reverse transcriptase expression through Myc and GC-rich Sp1 binding sites. J Virol. 2001;75:5559-5566.
74. Veldman T, Liu X, Yuan H, Schlegel R. Human papillomavirus E6 and Myc proteins associate in vivo and bind to and cooperatively activate the telomerase reverse transcriptase promoter. Proc Natl Acad Sci USA. 2003;100:8211-8216.
75. Liu X, Yuan H, Fu B, et al. The E6AP ubiquitin ligase is required for transactivation of the hTERT promoter by the human papillomavirus E6 oncoprotein. J Biol Chem. 2005;280:10807-10816.
76. Xiong J, Fan S, Meng Q, et al. BRCA1 inhibition of telomerase activity in cultured cells. Mol Cell Biol. 2003;23:8668-8690.
77. Gross-Mesilaty S, Reinstein E, Bercovich B, et al. Basal and human papillomavirus E6 oncoprotein-induced degradation of Myc proteins by the ubiquitin pathway. Proc Natl Acad Sci USA. 1998;95:8058-8063.
78. Nikiforov MA, Chandriani S, Park J, et al. TRRAP-dependent and TRRAP-independent transcriptional activation by Myc family oncoproteins. Mol Cell Biol. 2002;22:5054-5063.
79. Goueli BS, Janknecht R. Regulation of telomerase reverse transcriptase gene activity by upstream stimulatory factor. Oncogene. 2003;22:8042-8047.
80. McMurray HR, McCance DJ. Human papillomavirus type 16 E6 activates TERT gene transcription through induction of c-Myc and release of USF-mediated repression. J Virol. 2003;77:9852-9861.
81. Takakura M, Kyo S, Inoue M, Wright WE, Shay JW. Function of AP-1 in transcription of the telomerase reverse transcriptase gene (TERT) in human and mouse cells. Mol Cell Biol. 2005;25:8037-8043.
82. Alfonso-De Matte MY, Yang H, Evans MS, Cheng JQ, Kruk PA. Telomerase is regulated by c-Jun NH2-terminal kinase in ovarian surface epithelial cells. Cancer Res. 2002;62:4575-4578.
83. Mori N, Fujii M, Iwai K, et al. Constitutive activation of transcription factor AP-1 in primary adult T-cell leukemia cells. Blood. 2000;95:3915-3921.
84. Xu X, Heidenreich O, Kitajima I, et al. Constitutively activated JNK is associated with HTLV-1 mediated tumorigenesis. Oncogene. 1996;13:135-142.
85. Kieser A, Kilger E, Gires O, Ueffing M, Kolch W, Hammerschmidt W. Epstein-Barr virus latent membrane protein-1 triggers AP-1 activity via the c-Jun N-terminal kinase cascade. EMBO J. 1997;16:6478-6485.
86. Ding L, Li L, Yang J, et al. Latent membrane protein 1 encoded by Epstein-Barr virus induces telomerase activity via p16INK4A/Rb/E2F1 and JNK signaling pathways. J Med Virol. 2007;79:1153-1163.
87. Cong YS, Bacchetti S. Histone deacetylation is involved in the transcriptional repression of hTERT in normal human cells. J Biol Chem. 2000;275:35665-35668.
88. Hou M, Wang X, Popov N, et al. The histone deacetylase inhibitor trichostatin A derepresses the telomerase reverse transcriptase (hTERT) gene in human cells. Exp Cell Res. 2002;274:25-34.
89. James MA, Lee JH, Klingelhutz AJ. HPV16-E6 associated hTERT promoter acetylation is E6AP dependent, increased in later passage cells and enhanced by loss of p300. Int J Cancer. 2006;119:1878-1885.
90. Kirch HC, Ruschen S, Brockmann D, et al. Tumor-specific activation of hTERT-derived promoters by tumor suppressive E1A-mutants involves recruitment of p300/CBP/HAT and suppression of HDAC-1 and defines a combined tumor targeting and suppression system. Oncogene. 2002;21:7991-8000.
91. Ge Z, Liu C, Bjorkholm M, Gruber A, Xu D. Mitogen-activated protein kinase cascade-mediated histone H3 phosphorylation is critical for telomerase reverse transcriptase expression/telomerase activation induced by proliferation. Mol Cell Biol. 2006;26:230-237.
92. Eliopoulos AG, Young LS. Activation of the cJun N-terminal kinase (JNK) pathway by the Epstein-Barr virus-encoded latent membrane protein 1 (LMP1). Oncogene. 1998;16:1731-1742.
93. Hamza MS, Reyes RA, Izumiya Y, Wisdom R, Kung HJ, Luciw PA. ORF36 protein kinase of Kaposi's sarcoma herpesvirus activates the c-Jun N-terminal kinase signaling pathway. J Biol Chem. 2004;279:38325-38330.
94. Widschwendter A, Muller HM, Hubalek MM, et al. Methylation status and expression of human telomerase reverse transcriptase in ovarian and cervical cancer. Gynecol Oncol. 2004;93:407-416.
95. Devereux TR, Horikawa I, Anna CH, Annab LA, Afshari CA, Barrett JC. DNA methylation analysis of the promoter region of the human telomerase reverse transcriptase (hTERT) gene. Cancer Res. 1999;59:6087-6090.
96. Kitagawa Y, Kyo S, Takakura M, et al. Demethylating reagent 5-azacytidine inhibits telomerase activity in human prostate cancer cells through transcriptional repression of hTERT. Clin Cancer Res. 2000;6:2868-2875.
97. Guilleret I, Yan P, Grange F, Braunschweig R, Bosman FT, Benhattar J. Hypermethylation of the human telomerase catalytic subunit (hTERT) gene correlates with telomerase activity. Int J Cancer. 2002;101:335-341.
98. Ferber MJ, Montoya DP, Yu C, et al. Integrations of the hepatitis B virus (HBV) and human papillomavirus (HPV) into the human telomerase reverse transcriptase (hTERT) gene in liver and cervical cancers. Oncogene. 2003;22:3813-3820.
99. Paterlini-Brechot P, Saigo K, Murakami Y, et al. Hepatitis B virus-related insertional mutagenesis occurs frequently in human liver cancers and recurrently targets human telomerase gene. Oncogene. 2003;22:3911-3916.
100. Horikawa I, Barrett JC. Transcriptional regulation of the telomerase hTERT gene as a target for cellular and viral oncogenic mechanisms. Carcinogenesis. 2003;24:1167-1176.
101. Horikawa I, Barrett JC. cis-Activation of the human telomerase gene (hTERT) by the hepatitis B virus genome. J Natl Cancer Inst. 2001;93:1171-1173.
102. Heselmeyer K, Schrock E, du MS, et al. Gain of chromosome 3q defines the transition from severe dysplasia to invasive carcinoma of the uterine cervix. Proc Natl Acad Sci USA. 1996;93:479-484.
103. Hopman AH, Theelen W, Hommelberg PP, et al. Genomic integration of oncogenic HPV and gain of the human telomerase gene TERC at 3q26 are strongly associated events in the progression of uterine cervical dysplasia to invasive cancer. J Pathol. 2006;210:412-419.
104. Chang JT, Lu YC, Chen YJ, et al. hTERT phosphorylation by PKC is essential for telomerase holoprotein integrity and enzyme activity in head neck cancer cells. Br J Cancer. 2006;94:870-878.
105. Kim YW, Hur SY, Kim TE, et al. Protein kinase C modulates telomerase activity in human cervical cancer cells. Exp Mol Med. 2001;33:156-163.
106. Kang SS, Kwon T, Kwon DY, Do SI. Akt protein kinase enhances human telomerase activity through phosphorylation of telomerase reverse transcriptase subunit. J Biol Chem. 1999;274:13085-13090.
107. Akiyama M, Hideshima T, Hayashi T, et al. Nuclear factor-kappaB p65 mediates tumor necrosis factor alpha-induced nuclear translocation of telomerase reverse transcriptase protein. Cancer Res. 2003;63:18-21.
108. Li H, Zhao LL, Funder JW, Liu JP. Protein phosphatase 2A inhibits nuclear telomerase activity in human breast cancer cells. J Biol Chem. 1997;272:16729-16732.
109. Ding L, Li LL, Yang J, et al. Epstein-Barr virus encoded latent membrane protein 1 modulates nuclear translocation of telomerase reverse transcriptase protein by activating nuclear factor-kappaB p65 in human nasopharyngeal carcinoma cells. Int J Biochem Cell Biol. 2005;37:1881-1889.
110. Katzenellenbogen RA, Egelkrout EM, Vliet-Gregg P, Gewin LC, Gafken PR, Galloway DA. NFX1-123 and poly(A) binding proteins synergistically augment activation of telomerase in human papillomavirus type 16 E6-expressing cells. J Virol. 2007;81:3786-3796.
111. Evans SK, Lundblad V. Positive and negative regulation of telomerase access to the telomere. J Cell Sci. 2000;113:3357-3364.
112. Smogorzewska A, van Steensel B, Bianchi A, et al. Control of human telomere length by TRF1 and TRF2. Mol Cell Biol. 2000;20:1659-1668.
113. Karlseder J, Broccoli D, Dai Y, Hardy S, de Lange T. p53- and ATM-dependent apoptosis induced by telomeres lacking TRF2. Science. 1999;283:1321-1325.
114. Kim SH, Beausejour C, Davalos AR, Kaminker P, Heo SJ, Campisi J. TIN2 mediates functions of TRF2 at human telomeres. J Biol Chem. 2004;279:43799-43804.
115. Klapper W, Krams M, Qian W, Janssen D, Parwaresch R. Telomerase activity in B-cell non-Hodgkin lymphomas is regulated by hTERT transcription and correlated with telomere-binding protein expression but uncoupled from proliferation. Br J Cancer. 2003;89:713-719.
116. Zhou XZ, Lu KP. The Pin2/TRF1-interacting protein PinX1 is a potent telomerase inhibitor. Cell. 2001;107:347-359.
117. Oh BK, Chae KJ, Park C, Park YN. Molecular analysis of PinX1 in human hepatocellular carcinoma. Oncol Rep. 2004;12:861-866.
118. Lin SY, Elledge SJ. Multiple tumor suppressor pathways negatively regulate telomerase. Cell. 2003;113:881-889.
119. Romanczuk H, Thierry F, Howley PM. Mutational analysis of cis elements involved in E2 modulation of human papillomavirus type 16 P97 and type 18 P105 promoters. J Virol. 1990;64:2849-2859.
120. Demeret C, Desaintes C, Yaniv M, Thierry F. Different mechanisms contribute to the E2-mediated transcriptional repression of human papillomavirus type 18 viral oncogenes. J Virol. 1997;71:9343-9349.
121. Wells SI, Francis DA, Karpova AY, Dowhanick JJ, Benson JD, Howley PM. Papillomavirus E2 induces senescence in HPV-positive cells via pRB-and p21(CIP)-dependent pathways. EMBO J. 2000;19:5762-5771.
122. Lee D, Kim HZ, Jeong KW, et al. Human papillomavirus E2 down-regulates the human telomerase reverse transcriptase promoter. J Biol Chem. 2002;277:27748-27756.
123. Galloway DA, Gewin LC, Myers H, et al. Regulation of telomerase by human papillomaviruses. Cold Spring Harb Symp Quant Biol. 2005;70:209-215.
124. Gutsch DE, Holley-Guthrie EA, Zhang Q, et al. The bZIP transactivator of Epstein-Barr virus, BZLF1, functionally and physically interacts with the p65 subunit of NF-kappa B. Mol Cell Biol. 1994;14:1939-1948.
125. Sun Q, Zachariah S, Chaudhary PM. The human herpes virus 8-encoded viral FLICE-inhibitory protein induces cellular transformation via NF-kappaB activation. J Biol Chem. 2003;278:52437-52445.
126. Lin R, Genin P, Mamane Y, et al. HHV-8 encoded vIRF-1 represses the interferon antiviral response by blocking IRF-3 recruitment of the CBP/p300 coactivators. Oncogene. 2001;20:800-811.
127. Lundin M, Monne M, Widell A, Von Heijne G, Persson MA. Topology of the membrane-associated hepatitis C virus protein NS4B. J Virol. 2003;77:5428-5438.
128. Macdonald A, Harris M. Hepatitis C virus NS5A: tales of a promiscuous protein. J Gen Virol. 2004;85:2485-2502.