Oncogenic Human Papillomaviruses Activate the Tumor-Associated Lens Epithelial-Derived Growth Factor (LEDGF) Gene

PLoS Pathogens

Volumn 10, Issue 3, 2014, Pages

  Leitz, Jenny ^a   Reuschenbach, Miriam ^b   Lohrey, Claudia ^a   Honegger, Anja ^a   Accardi, Rosita ^c   Tommasino, Massimo ^c   Llano, Manuel ^d   von Knebel Doeberitz, Magnus ^b   Hoppe Seyler, Karin ^a   Hoppe Seyler, Felix ^a  

^a GERMAN CANCER RESEARCH CENTER DKFZ   (Germany)

^b UNIVERSITY OF HEIDELBERG   (Germany)

^c INTERNATIONAL AGENCY FOR RESEARCH ON CANCER   (France)

^d UNIVERSITY OF TEXAS AT EL PASO   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EPITHELIAL DERIVED GROWTH FACTOR; GROWTH FACTOR; UNCLASSIFIED DRUG;

ARTICLE; CARCINOGENESIS; CELL CYCLE; CELL SURVIVAL; COLONY FORMATION; CONTROLLED STUDY; DNA DAMAGE; E6 ONCOGENE; E7 ONCOGENE; GENE ACTIVATION; GENE EXPRESSION; GENE SILENCING; HISTOLOGY; HUMAN CELL; IMMUNOBLOTTING; IMMUNOHISTOCHEMISTRY; KERATINOCYTE; LUCIFERASE ASSAY; ONCOGENE; PROTEIN EXPRESSION; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; RNA INTERFERENCE; TUMOR CELL; UTERINE CERVIX EPITHELIUM; VIRAL GENE DELIVERY SYSTEM; WART VIRUS;

CELL LINE; CELL TRANSFORMATION, NEOPLASTIC; FEMALE; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; IMMUNOBLOTTING; IMMUNOHISTOCHEMISTRY; INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS; ONCOGENE PROTEINS, VIRAL; PAPILLOMAVIRUS E7 PROTEINS; PAPILLOMAVIRUS INFECTIONS; REPRESSOR PROTEINS; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; RNA, SMALL INTERFERING; TRANSFECTION; UTERINE CERVICAL NEOPLASMS;

EID: 84897414138     PISSN: 15537366     EISSN: 15537374     Source Type: Journal    
DOI: 10.1371/journal.ppat.1003957     Document Type: Article

References (80)

1. Zur Hausen H, (2009) The search for infectious causes of human cancers: where and why. Virology 392: 1-10.
2. Weinstein IB, Joe A, (2008) Oncogene addiction. Cancer Res 68: 3077-3080 discussion 3080.
3. zur Hausen H, (2002) Papillomaviruses and cancer: from basic studies to clinical application. Nat Rev Cancer 2: 342-350.
4. McLaughlin-Drubin ME, Munger K, (2009) Oncogenic activities of human papillomaviruses. Virus Res 143: 195-208.
5. Moody CA, Laimins LA, (2010) Human papillomavirus oncoproteins: pathways to transformation. Nat Rev Cancer 10: 550-560.
6. Hoppe-Seyler F, Hoppe-Seyler K, (2011) Emerging topics in human tumor virology. Int J Cancer 129: 1289-1299.
7. Butz K, Shahabeddin L, Geisen C, Spitkovsky D, Ullmann A, et al. (1995) Functional p53 protein in human papillomavirus-positive cancer cells. Oncogene 10: 927-936.
8. Butz K, Denk C, Ullmann A, Scheffner M, Hoppe-Seyler F, (2000) Induction of apoptosis in human papillomaviruspositive cancer cells by peptide aptamers targeting the viral E6 oncoprotein. Proc Natl Acad Sci U S A 97: 6693-6697.
9. 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: 12513-12518.
10. Wells SI, Francis DA, Karpova AY, Dowhanick JJ, Benson JD, et al. (2000) Papillomavirus E2 induces senescence in HPV-positive cells via pRB- and p21(CIP)-dependent pathways. EMBO J 19: 5762-5771.
11. Butz K, Ristriani T, Hengstermann A, Denk C, Scheffner M, et al. (2003) siRNA targeting of the viral E6 oncogene efficiently kills human papillomavirus-positive cancer cells. Oncogene 22: 5938-5945.
12. Hall AH, Alexander KA, (2003) RNA interference of human papillomavirus type 18 E6 and E7 induces senescence in HeLa cells. J Virol 77: 6066-6069.
13. Kuner R, Vogt M, Sultmann H, Buness A, Dymalla S, et al. (2007) Identification of cellular targets for the human papillomavirus E6 and E7 oncogenes by RNA interference and transcriptome analyses. J Mol Med (Berl) 85: 1253-1262.
14. Cherepanov P, Maertens G, Proost P, Devreese B, Van Beeumen J, et al. (2003) HIV-1 integrase forms stable tetramers and associates with LEDGF/p75 protein in human cells. J Biol Chem 278: 372-381.
15. Maertens G, Cherepanov P, Pluymers W, Busschots K, De Clercq E, et al. (2003) LEDGF/p75 is essential for nuclear and chromosomal targeting of HIV-1 integrase in human cells. J Biol Chem 278: 33528-33539.
16. Ciuffi A, Llano M, Poeschla E, Hoffmann C, Leipzig J, et al. (2005) A role for LEDGF/p75 in targeting HIV DNA integration. Nat Med 11: 1287-1289.
17. Llano M, Saenz DT, Meehan A, Wongthida P, Peretz M, et al. (2006) An essential role for LEDGF/p75 in HIV integration. Science 314: 461-464.
18. Daniels T, Zhang J, Gutierrez I, Elliot ML, Yamada B, et al. (2005) Antinuclear autoantibodies in prostate cancer: immunity to LEDGF/p75, a survival protein highly expressed in prostate tumors and cleaved during apoptosis. Prostate 62: 14-26.
19. Daugaard M, Kirkegaard-Sorensen T, Ostenfeld MS, Aaboe M, Hoyer-Hansen M, et al. (2007) Lens epithelium-derived growth factor is an Hsp70-2 regulated guardian of lysosomal stability in human cancer. Cancer Res 67: 2559-2567.
20. Basu A, Rojas H, Banerjee H, Cabrera IB, Perez KY, et al. (2012) Expression of the stress response oncoprotein LEDGF/p75 in human cancer: a study of 21 tumor types. PLoS One 7: e30132.
21. Ahuja HG, Hong J, Aplan PD, Tcheurekdjian L, Forman SJ, et al. (2000) t(9;11)(p22;p15) in acute myeloid leukemia results in a fusion between NUP98 and the gene encoding transcriptional coactivators p52 and p75-lens epithelium-derived growth factor (LEDGF). Cancer Res 60: 6227-6229.
22. Huang TS, Myklebust LM, Kjarland E, Gjertsen BT, Pendino F, et al. (2007) LEDGF/p75 has increased expression in blasts from chemotherapy-resistant human acute myelogenic leukemia patients and protects leukemia cells from apoptosis in vitro. Mol Cancer 6: 31.
23. Yokoyama A, Cleary ML, (2008) Menin critically links MLL proteins with LEDGF on cancer-associated target genes. Cancer Cell 14: 36-46.
24. Cohen B, Addadi Y, Sapoznik S, Meir G, Kalchenko V, et al. (2009) Transcriptional regulation of vascular endothelial growth factor C by oxidative and thermal stress is mediated by lens epithelium-derived growth factor/p75. Neoplasia 11: 921-933.
25. Bhargavan B, Fatma N, Chhunchha B, Singh V, Kubo E, et al. (2012) LEDGF gene silencing impairs the tumorigenicity of prostate cancer DU145 cells by abating the expression of Hsp27 and activation of the Akt/ERK signaling pathway. Cell Death Dis 3: e316.
26. Sapoznik S, Cohen B, Tzuman Y, Meir G, Ben-Dor S, et al. (2009) Gonadotropin-regulated lymphangiogenesis in ovarian cancer is mediated by LEDGF-induced expression of VEGF-C. Cancer Res 69: 9306-9314.
27. Singh DP, Ohguro N, Chylack LT Jr, Shinohara T, (1999) Lens epithelium-derived growth factor: increased resistance to thermal and oxidative stresses. Invest Ophthalmol Vis Sci 40: 1444-1451.
28. Singh DP, Ohguro N, Kikuchi T, Sueno T, Reddy VN, et al. (2000) Lens epithelium-derived growth factor: effects on growth and survival of lens epithelial cells, keratinocytes, and fibroblasts. Biochem Biophys Res Commun 267: 373-381.
29. Nakamura M, Singh DP, Kubo E, Chylack LT Jr, Shinohara T, (2000) LEDGF: survival of embryonic chick retinal photoreceptor cells. Invest Ophthalmol Vis Sci 41: 1168-1175.
30. Matsui H, Lin LR, Singh DP, Shinohara T, Reddy VN, (2001) Lens epithelium-derived growth factor: increased survival and decreased DNA breakage of human RPE cells induced by oxidative stress. Invest Ophthalmol Vis Sci 42: 2935-2941.
31. Wu X, Daniels T, Molinaro C, Lilly MB, Casiano CA, (2002) Caspase cleavage of the nuclear autoantigen LEDGF/p75 abrogates its pro-survival function: implications for autoimmunity in atopic disorders. Cell Death Differ 9: 915-925.
32. Fatma N, Kubo E, Chylack LT Jr, Shinohara T, Akagi Y, et al. (2004) LEDGF regulation of alcohol and aldehyde dehydrogenases in lens epithelial cells: stimulation of retinoic acid production and protection from ethanol toxicity. Am J Physiol Cell Physiol 287: C508-516.
33. Daugaard M, Baude A, Fugger K, Povlsen LK, Beck H, et al. (2012) LEDGF (p75) promotes DNA-end resection and homologous recombination. Nat Struct Mol Biol 19: 803-810.
34. Machida S, Chaudhry P, Shinohara T, Singh DP, Reddy VN, et al. (2001) Lens epithelium-derived growth factor promotes photoreceptor survival in light-damaged and RCS rats. Invest Ophthalmol Vis Sci 42: 1087-1095.
35. Scheffner M, Werness BA, Huibregtse JM, Levine AJ, Howley PM, (1990) The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53. Cell 63: 1129-1136.
36. Hwang ES, Riese DJ 2nd, Settleman J, Nilson LA, Honig J, et al. (1993) Inhibition of cervical carcinoma cell line proliferation by the introduction of a bovine papillomavirus regulatory gene. J Virol 67: 3720-3729.
37. Dowhanick JJ, McBride AA, Howley PM, (1995) Suppression of cellular proliferation by the papillomavirus E2 protein. J Virol 69: 7791-7799.
38. Holland D, Hoppe-Seyler K, Schuller B, Lohrey C, Maroldt J, et al. (2008) Activation of the enhancer of zeste homologue 2 gene by the human papillomavirus E7 oncoprotein. Cancer Res 68: 9964-9972.
39. Watson PA, Hanauske-Abel HH, Flint A, Lalande M, (1991) Mimosine reversibly arrests cell cycle progression at the G1-S phase border. Cytometry 12: 242-246.
40. Banfalvi G, (2011) Overview of cell synchronization. Methods Mol Biol 761: 1-23.
41. Ge H, Si Y, Roeder RG, (1998) Isolation of cDNAs encoding novel transcription coactivators p52 and p75 reveals an alternate regulatory mechanism of transcriptional activation. EMBO J 17: 6723-6729.
42. Becker B, Cooper MA, (2013) Aminoglycoside antibiotics in the 21st century. ACS Chem Biol 8: 105-115.
43. Gaggelli E, Gaggelli N, Molteni E, Valensin G, Balenci D, et al. (2010) Coordination pattern, solution structure and DNA damage studies of the copper(II) complex with the unusual aminoglycoside antibiotic hygromycin B. Dalton Trans 39: 9830-9837.
44. Bonner WM, Redon CE, Dickey JS, Nakamura AJ, Sedelnikova OA, et al. (2008) GammaH2AX and cancer. Nat Rev Cancer 8: 957-967.
45. Klaes R, Friedrich T, Spitkovsky D, Ridder R, Rudy W, et al. (2001) Overexpression of p16(INK4A) as a specific marker for dysplastic and neoplastic epithelial cells of the cervix uteri. Int J Cancer 92: 276-284.
46. Nakamura H, Izumoto Y, Kambe H, Kuroda T, Mori T, et al. (1994) Molecular cloning of complementary DNA for a novel human hepatoma-derived growth factor. Its homology with high mobility group-1 protein. J Biol Chem 269: 25143-25149.
47. Poeschla EM, (2008) Integrase, LEDGF/p75 and HIV replication. Cell Mol Life Sci 65: 1403-1424.
48. Maertens G, Cherepanov P, Debyser Z, Engelborghs Y, Engelman A, (2004) Identification and characterization of a functional nuclear localization signal in the HIV-1 integrase interactor LEDGF/p75. J Biol Chem 279: 33421-33429.
49. Llano M, Vanegas M, Hutchins N, Thompson D, Delgado S, et al. (2006) Identification and characterization of the chromatin-binding domains of the HIV-1 integrase interactor LEDGF/p75. J Mol Biol 360: 760-773.
50. Eidahl JO, Crowe BL, North JA, McKee CJ, Shkriabai N, et al. (2013) Structural basis for high-affinity binding of LEDGF PWWP to mononucleosomes. Nucleic Acids Res 41: 3924-3936.
51. Fatma N, Singh DP, Shinohara T, Chylack LT Jr, (2001) Transcriptional regulation of the antioxidant protein 2 gene, a thiol-specific antioxidant, by lens epithelium-derived growth factor to protect cells from oxidative stress. J Biol Chem 276: 48899-48907.
52. Singh DP, Fatma N, Kimura A, Chylack LT Jr, Shinohara T, (2001) LEDGF binds to heat shock and stress-related element to activate the expression of stress-related genes. Biochem Biophys Res Commun 283: 943-955.
53. Maertens GN, Cherepanov P, Engelman A, (2006) Transcriptional co-activator p75 binds and tethers the Myc-interacting protein JPO2 to chromatin. J Cell Sci 119: 2563-2571.
54. Huang A, Ho CS, Ponzielli R, Barsyte-Lovejoy D, Bouffet E, et al. (2005) Identification of a novel c-Myc protein interactor, JPO2, with transforming activity in medulloblastoma cells. Cancer Res 65: 5607-5619.
55. Wu G, Lee WH, (2006) CtIP, a multivalent adaptor connecting transcriptional regulation, checkpoint control and tumor suppression. Cell Cycle 5: 1592-1596.
56. Sartori AA, Lukas C, Coates J, Mistrik M, Fu S, et al. (2007) Human CtIP promotes DNA end resection. Nature 450: 509-514.
57. Szczepanik W, Dworniczek E, Ciesiolka J, Wrzesinski J, Skala J, et al. (2003) In vitro oxidative activity of cupric complexes of kanamycin A in comparison to in vivo bactericidal efficacy. J Inorg Biochem 94: 355-364.
58. Balenci D, Bonechi G, D'Amelio N, Gaggelli E, Gaggelli N, et al. (2009) Structural features and oxidative stress towards plasmid DNA of apramycin copper complex. Dalton Trans 7: 1123-1130.
59. Payne S, Kernohan NM, Walker F, (1996) Proliferation in the normal cervix and in preinvasive cervical lesions. J Clin Pathol 49: 667-671.
60. Desfarges S, Abderrahmani A, Hernandez-Novoa B, Munoz M, Ciuffi A, (2011) LEDGF/p75 TATA-less promoter is driven by the transcription factor Sp1. J Mol Biol 414: 177-193.
61. Singh DP, Bhargavan B, Chhunchha B, Kubo E, Kumar A, et al. (2012) Transcriptional protein Sp1 regulates LEDGF transcription by directly interacting with its cis-elements in GC-rich region of TATA-less gene promoter. PLoS One 7: e37012.
62. Bhargavan B, Chhunchha B, Fatma N, Kubo E, Kumar A, et al. (2013) Epigenetic repression of LEDGF during UVB exposure by recruitment of SUV39H1 and HDAC1 to the Sp1-responsive elements within LEDGF promoter CpG island. Epigenetics 8: 268-280.
63. Vanegas M, Llano M, Delgado S, Thompson D, Peretz M, et al. (2005) Identification of the LEDGF/p75 HIV-1 integrase-interaction domain and NLS reveals NLS-independent chromatin tethering. J Cell Sci 118: 1733-1743.
64. Nishizawa Y, Usukura J, Singh DP, Chylack LT Jr, Shinohara T, (2001) Spatial and temporal dynamics of two alternatively spliced regulatory factors, lens epithelium-derived growth factor (ledgf/p75) and p52, in the nucleus. Cell Tissue Res 305: 107-114.
65. Singh DP, Kubo E, Takamura Y, Shinohara T, Kumar A, et al. (2006) DNA binding domains and nuclear localization signal of LEDGF: contribution of two helix-turn-helix (HTH)-like domains and a stretch of 58 amino acids of the N-terminal to the trans-activation potential of LEDGF. J Mol Biol 355: 379-394.
66. Chylack LT Jr, Fu L, Mancini R, Martin-Rehrmann MD, Saunders AJ, et al. (2004) Lens epithelium-derived growth factor (LEDGF/p75) expression in fetal and adult human brain. Exp Eye Res 79: 941-948.
67. Sugiura K, Muro Y, Nishizawa Y, Okamoto M, Shinohara T, et al. (2007) LEDGF/DFS70, a major autoantigen of atopic dermatitis, is a component of keratohyalin granules. J Invest Dermatol 127: 75-80.
68. Crum CP, (2000) Contemporary theories of cervical carcinogenesis: the virus, the host, and the stem cell. Mod Pathol 13: 243-251.
69. Sharma P, Singh DP, Fatma N, Chylack LT Jr, Shinohara T, (2000) Activation of LEDGF gene by thermal-and oxidative-stresses. Biochem Biophys Res Commun 276: 1320-1324.
70. Caldeira S, Zehbe I, Accardi R, Malanchi I, Dong W, et al. (2003) The E6 and E7 proteins of the cutaneous human papillomavirus type 38 display transforming properties. J Virol 77: 2195-2206.
71. Cullmann C, Hoppe-Seyler K, Dymalla S, Lohrey C, Scheffner M, et al. (2009) Oncogenic human papillomaviruses block expression of the B-cell translocation gene-2 tumor suppressor gene. Int J Cancer 125: 2014-2020.
72. Basu A, Drame A, Munoz R, Gijsbers R, Debyser Z, et al. (2012) Pathway specific gene expression profiling reveals oxidative stress genes potentially regulated by transcription co-activator LEDGF/p75 in prostate cancer cells. Prostate 72: 597-611.
73. Honegger A, Leitz J, Bulkescher J, Hoppe-Seyler K, Hoppe-Seyler F, (2013) Silencing of human papillomavirus (HPV) E6/E7 oncogene expression affects both the contents and the amounts of extracellular microvesicles released from HPV-positive cancer cells. Int J Cancer 133: 1631-1642.
74. Hoppe-Seyler K, Sauer P, Lohrey C, Hoppe-Seyler F, (2012) The inhibitors of nucleotide biosynthesis leflunomide, FK778, and mycophenolic acid activate hepatitis B virus replication in vitro. Hepatology 56: 9-16.
75. Garcia-Rivera JA, Bueno MT, Morales E, Kugelman JR, Rodriguez DF, et al. (2010) Implication of serine residues 271, 273, and 275 in the human immunodeficiency virus type 1 cofactor activity of lens epithelium-derived growth factor/p75. J Virol 84: 740-752.
76. Spangle JM, Ghosh-Choudhury N, Munger K, (2012) Activation of cap-dependent translation by mucosal human papillomavirus E6 proteins is dependent on the integrity of the LXXLL binding motif. J Virol 86: 7466-7472.
77. Crnkovic-Mertens I, Muley T, Meister M, Hartenstein B, Semzow J, et al. (2006) The anti-apoptotic livin gene is an important determinant for the apoptotic resistance of non-small cell lung cancer cells. Lung Cancer 54: 135-142.
78. Livak KJ, Schmittgen TD, (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25: 402-408.
79. Watson JV, Chambers SH, Smith PJ, (1987) A pragmatic approach to the analysis of DNA histograms with a definable G1 peak. Cytometry 8: 1-8.
80. Wagener N, Bulkescher J, Macher-Goeppinger S, Karapanagiotou-Schenkel I, Hatiboglu G, et al. (2013) Endogenous BTG2 expression stimulates migration of bladder cancer cells and correlates with poor clinical prognosis for bladder cancer patients. Br J Cancer 108: 973-982.