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Nucleoside diphosphate kinase/Nm23 and Epstein–Barr virus

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Abstract

Nm23-H1 was discovered as the first metastasis suppressor gene about 20 years ago. Since then, extensive work has contributed to understanding its role in various cellular signaling pathways. Its association with a range of human cancers as well as its ability to regulate cell cycle and suppress metastasis has been explored. We have determined that the EBV-encoded nuclear antigens, EBNA3C and EBNA1, required for EBV-mediated lymphoproliferation and for maintenance EBV genome extrachromosomally in dividing mammalian cells, respectively, target and disrupt the physiological role of Nm23-H1 in the context of cell proliferation and cell migration. This review will focus on the interaction of Nm23-H1 with the Epstein–Barr virus nuclear antigens, EBNA3C and EBNA1 and the functional significance of this interaction as it relates to EBV pathogenesis.

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References

  1. Titus B, Schwartz MA, Theodorescu D (2005) Rho proteins in cell migration and metastasis. Crit Rev Eukaryot Gene Expr 15:103–114. doi:10.1615/CritRevEukaryotGeneExpr.v15.i2.20

    Article  PubMed  CAS  Google Scholar 

  2. Steeg PS (2004) Perspectives on classic article: metastasis suppressor genes. J Natl Cancer Inst 96:E4

    PubMed  Google Scholar 

  3. Lacombe ML, Milon L, Munier A, Mehus JG, Lambeth DO (2000) The human Nm23/nucleoside diphosphate kinases. J Bioenerg Biomembr 32:247–258. doi:10.1023/A:1005584929050

    Article  PubMed  CAS  Google Scholar 

  4. Russell RL, Pedersen AN, Kantor J, Geisinger K, Long R, Zbieranski N, Townsend A, Shelton B, Brunner N, Kute TE (1998) Relationship of nm23 to proteolytic factors, proliferation and motility in breast cancer tissues and cell lines. Br J Cancer 78:710–717

    PubMed  CAS  Google Scholar 

  5. Tee YT, Chen GD, Lin LY, Ko JL, Wang PH (2006) Nm23-H1: a metastasis-associated gene. Taiwan J Obstet Gynecol 45:107–113

    Article  PubMed  Google Scholar 

  6. Kieff E, Rickinson AB (2002) Epstein–Barr virus and its replication. In: Knipe DM, Howley PM, Griffin DE, Lamb RA, Martin MA, Roizman B, Straus SE (eds) Fundamental virology. Lippincott Williams and Wilkins, Philadelphia

  7. Burkitt D (1958) A sarcoma involving the jaws in African children. Br J Surg 46:218–223. doi:10.1002/bjs.18004619704

    Article  PubMed  CAS  Google Scholar 

  8. Epstein MA, Achong BG, Barr YM (1964) Virus particles in cultured lymphoblasts from Burkitt’s lymphoma. Lancet 1:702–703. doi:10.1016/S0140-6736(64)91524-7

    Article  PubMed  CAS  Google Scholar 

  9. Henle G, Henle W, Diehl V (1968) Relation of Burkitt’s tumor-associated herpes-type virus to infectious mononucleosis. Proc Natl Acad Sci USA 59:94–101. doi:10.1073/pnas.59.1.94

    Article  PubMed  CAS  Google Scholar 

  10. zur Hausen H, Schulte-Holthausen H, Klein G, Henle W, Henle G, Clifford P, Santesson L (1970) EBV DNA in biopsies of Burkitt tumours and anaplastic carcinomas of the nasopharynx. Nature 228:1056–1058. doi:10.1038/2281056a0

    Article  PubMed  CAS  Google Scholar 

  11. Hasserjian RP, Harris NL (2007) NK-cell lymphomas and leukemias: a spectrum of tumors with variable manifestations and immunophenotype. Am J Clin Pathol 127:860–868. doi:10.1309/2F39NX1AL3L54WU8

    Article  PubMed  CAS  Google Scholar 

  12. Said JW, Tasaka T, Takeuchi S, Asou H, de Vos S, Cesarman E, Knowles DM, Koeffler HP (1996) Primary effusion lymphoma in women: report of two cases of Kaposi’s sarcoma herpes virus-associated effusion-based lymphoma in human immunodeficiency virus-negative women. Blood 88:3124–3128

    PubMed  CAS  Google Scholar 

  13. Johansson B, Klein G, Henle W, Henle G (1970) Epstein–Barr virus (EBV)-associated antibody patterns in malignant lymphoma and leukemia. I. Hodgkin’s disease. Int J Cancer 6:450–462. doi:10.1002/ijc.2910060316

    Article  PubMed  CAS  Google Scholar 

  14. Purtilo DT, Yang JP, Allegra S, DeFlorio D, Hutt LM, Soltani M, Vawter G (1977) Hematopathology and pathogenesis of the X-linked recessive lymphoproliferative syndrome. Am J Med 62:225–233. doi:10.1016/0002-9343(77)90318-7

    Article  PubMed  CAS  Google Scholar 

  15. Bar RS, DeLor CJ, Clausen KP, Hurtubise P, Henle W, Hewetson JF (1974) Fatal infectious mononucleosis in a family. N Engl J Med 290:363–367

    Article  PubMed  CAS  Google Scholar 

  16. Alfieri C, Birkenbach M, Kieff E (1991) Early events in Epstein–Barr virus infection of human B lymphocytes. Virology 181:595–608. doi:10.1016/0042-6822(91)90893-G

    Article  PubMed  CAS  Google Scholar 

  17. Lee MA, Diamond ME, Yates JL (1999) Genetic evidence that EBNA-1 is needed for efficient, stable latent infection by Epstein–Barr virus. J Virol 73:2974–2982

    PubMed  CAS  Google Scholar 

  18. Yates JL, Camiolo SM, Bashaw JM (2000) The minimal replicator of Epstein–Barr virus oriP. J Virol 74:4512–4522. doi:10.1128/JVI.74.10.4512-4522.2000

    Article  PubMed  CAS  Google Scholar 

  19. Inman GJ, Farrell PJ (1995) Epstein–Barr virus EBNA-LP and transcription regulation properties of pRB, p107 and p53 in transfection assays. J Gen Virol 76(Pt 9):2141–2149. doi:10.1099/0022-1317-76-9-2141

    Article  PubMed  CAS  Google Scholar 

  20. Cohen JI, Wang F, Mannick J, Kieff E (1989) Epstein–Barr virus nuclear protein 2 is a key determinant of lymphocyte transformation. Proc Natl Acad Sci USA 86:9558–9562. doi:10.1073/pnas.86.23.9558

    Article  PubMed  CAS  Google Scholar 

  21. Hammerschmidt W, Sugden B (1989) Genetic analysis of immortalizing functions of Epstein–Barr virus in human B lymphocytes. Nature 340:393–397. doi:10.1038/340393a0

    Article  PubMed  CAS  Google Scholar 

  22. Kaye KM, Izumi KM, Kieff E (1993) Epstein–Barr virus latent membrane protein 1 is essential for B-lymphocyte growth transformation. Proc Natl Acad Sci USA 90:9150–9154. doi:10.1073/pnas.90.19.9150

    Article  PubMed  CAS  Google Scholar 

  23. Tomkinson B, Robertson E, Kieff E (1993) Epstein–Barr virus nuclear proteins EBNA-3A and EBNA-3C are essential for B-lymphocyte growth transformation. J Virol 67:2014–2025

    PubMed  CAS  Google Scholar 

  24. Silins SL, Sculley TB (1995) Burkitt’s lymphoma cells are resistant to programmed cell death in the presence of the Epstein–Barr virus latent antigen EBNA-4. Int J Cancer 60:65–72. doi:10.1002/ijc.2910600110

    Article  PubMed  CAS  Google Scholar 

  25. Fruehling S, Longnecker R (1997) The immunoreceptor tyrosine-based activation motif of Epstein–Barr virus LMP2A is essential for blocking BCR-mediated signal transduction. Virology 235:241–251. doi:10.1006/viro.1997.8690

    Article  PubMed  CAS  Google Scholar 

  26. Rickinson AB, Moss DJ (1997) Human cytotoxic T lymphocyte responses to Epstein–Barr virus infection. Annu Rev Immunol 15:405–431. doi:10.1146/annurev.immunol.15.1.405

    Article  PubMed  CAS  Google Scholar 

  27. Maruo S, Johannsen E, Illanes D, Cooper A, Zhao B, Kieff E (2005) Epstein–Barr virus nuclear protein 3A domains essential for growth of lymphoblasts: transcriptional regulation through RBP-Jkappa/CBF1 is critical. J Virol 79:10171–10179. doi:10.1128/JVI.79.16.10171-10179.2005

    Article  PubMed  CAS  Google Scholar 

  28. Zimber-Strobl U, Strobl LJ (2001) EBNA2 and Notch signalling in Epstein–Barr virus mediated immortalization of B lymphocytes. Semin Cancer Biol 11:423–434. doi:10.1006/scbi.2001.0409

    Article  PubMed  CAS  Google Scholar 

  29. Le Roux A, Kerdiles B, Walls D, Dedieu JF, Perricaudet M (1994) The Epstein–Barr virus determined nuclear antigens EBNA-3A, -3B, and -3C repress EBNA-2-mediated transactivation of the viral terminal protein 1 gene promoter. Virology 205:596–602. doi:10.1006/viro.1994.1687

    Article  PubMed  CAS  Google Scholar 

  30. Marshall D, Sample C (1995) Epstein–Barr virus nuclear antigen 3C is a transcriptional regulator. J Virol 69:3624–3630

    PubMed  CAS  Google Scholar 

  31. Kienzle N, Young D, Silins SL, Sculley TB (1996) Induction of pleckstrin by the Epstein–Barr virus nuclear antigen 3 family. Virology 224:167–174. doi:10.1006/viro.1996.0518

    Article  PubMed  CAS  Google Scholar 

  32. Robertson ES, Ooka T, Kieff ED (1996) Epstein–Barr virus vectors for gene delivery to B lymphocytes. Proc Natl Acad Sci USA 93:11334–11340. doi:10.1073/pnas.93.21.11334

    Article  PubMed  CAS  Google Scholar 

  33. Subramanian C, Robertson ES (2002) The metastatic suppressor Nm23–H1 interacts with EBNA3C at sequences located between the glutamine- and proline-rich domains and can cooperate in activation of transcription. J Virol 76:8702–8709. doi:10.1128/JVI.76.17.8702-8709.2002

    Article  PubMed  CAS  Google Scholar 

  34. Zhao B, Sample CE (2000) Epstein–Barr virus nuclear antigen 3C activates the latent membrane protein 1 promoter in the presence of Epstein–Barr virus nuclear antigen 2 through sequences encompassing an spi-1/Spi-B binding site. J Virol 74:5151–5160. doi:10.1128/JVI.74.11.5151-5160.2000

    Article  PubMed  CAS  Google Scholar 

  35. Knight JS, Lan K, Subramanian C, Robertson ES (2003) Epstein–Barr virus nuclear antigen 3C recruits histone deacetylase activity and associates with the corepressors mSin3A and NCoR in human B-cell lines. J Virol 77:4261–4272. doi:10.1128/JVI.77.7.4261-4272.2003

    Article  PubMed  CAS  Google Scholar 

  36. Touitou R, Hickabottom M, Parker G, Crook T, Allday MJ (2001) Physical and functional interactions between the corepressor CtBP and the Epstein–Barr virus nuclear antigen EBNA3C. J Virol 75:7749–7755. doi:10.1128/JVI.75.16.7749-7755.2001

    Article  PubMed  CAS  Google Scholar 

  37. Steeg PS, Bevilacqua G, Kopper L, Thorgeirsson UP, Talmadge JE, Liotta LA, Sobel ME (1988) Evidence for a novel gene associated with low tumor metastatic potential. J Natl Cancer Inst 80:200–204. doi:10.1093/jnci/80.3.200

    Article  PubMed  CAS  Google Scholar 

  38. Pinon VP, Millot G, Munier A, Vassy J, Linares-Cruz G, Capeau J, Calvo F, Lacombe ML (1999) Cytoskeletal association of the A and B nucleoside diphosphate kinases of interphasic but not mitotic human carcinoma cell lines: specific nuclear localization of the B subunit. Exp Cell Res 246:355–367. doi:10.1006/excr.1998.4318

    Article  PubMed  CAS  Google Scholar 

  39. Hirayama R, Sawai S, Takagi Y, Mishima Y, Kimura N, Shimada N, Esaki Y, Kurashima C, Utsuyama M, Hirokawa K (1991) Positive relationship between expression of anti-metastatic factor (nm23 gene product or nucleoside diphosphate kinase) and good prognosis in human breast cancer. J Natl Cancer Inst 83:1249–1250. doi:10.1093/jnci/83.17.1249

    Article  PubMed  CAS  Google Scholar 

  40. Royds JA, Stephenson TJ, Rees RC, Shorthouse AJ, Silcocks PB (1993) Nm23 protein expression in ductal in situ and invasive human breast carcinoma. J Natl Cancer Inst 85:727–731. doi:10.1093/jnci/85.9.727

    Article  PubMed  CAS  Google Scholar 

  41. Hartsough MT, Steeg PS (2000) Nm23/nucleoside diphosphate kinase in human cancers. J Bioenerg Biomembr 32:301–308. doi:10.1023/A:1005597231776

    Article  PubMed  CAS  Google Scholar 

  42. Niitsu N, Okamoto M, Okabe-Kado J, Takagi T, Yoshida T, Aoki S, Honma Y, Hirano M (2001) Serum nm23–H1 protein as a prognostic factor for indolent non-Hodgkin’s lymphoma. Leukemia 15:832–839. doi:10.1038/sj.leu.2402105

    Article  PubMed  CAS  Google Scholar 

  43. Hailat N, Keim DR, Melhem RF, Zhu XX, Eckerskorn C, Brodeur GM, Reynolds CP, Seeger RC, Lottspeich F, Strahler JR et al (1991) High levels of p19/nm23 protein in neuroblastoma are associated with advanced stage disease and with N-myc gene amplification. J Clin Invest 88:341–345. doi:10.1172/JCI115299

    Article  PubMed  CAS  Google Scholar 

  44. Leone A, Seeger RC, Hong CM, Hu YY, Arboleda MJ, Brodeur GM, Stram D, Slamon DJ, Steeg PS (1993) Evidence for nm23 RNA overexpression, DNA amplification and mutation in aggressive childhood neuroblastomas. Oncogene 8:855–865

    PubMed  CAS  Google Scholar 

  45. Nakamori S, Ishikawa O, Ohhigashi H, Kameyama M, Furukawa H, Sasaki Y, Inaji H, Higashiyama M, Imaoka S, Iwanaga T et al (1993) Expression of nucleoside diphosphate kinase/nm23 gene product in human pancreatic cancer: an association with lymph node metastasis and tumor invasion. Clin Exp Metastasis 11:151–158. doi:10.1007/BF00114973

    Article  PubMed  CAS  Google Scholar 

  46. Oda Y, Naka T, Takeshita M, Iwamoto Y, Tsuneyoshi M (2000) Comparison of histological changes and changes in nm23 and c-MET expression between primary and metastatic sites in osteosarcoma: a clinicopathologic and immunohistochemical study. Hum Pathol 31:709–716. doi:10.1053/hupa.2000.8230

    Article  PubMed  CAS  Google Scholar 

  47. Kraeft SK, Traincart F, Mesnildrey S, Bourdais J, Veron M, Chen LB (1996) Nuclear localization of nucleoside diphosphate kinase type B (nm23-H2) in cultured cells. Exp Cell Res 227:63–69. doi:10.1006/excr.1996.0250

    Article  PubMed  CAS  Google Scholar 

  48. Postel EH, Berberich SJ, Flint SJ, Ferrone CA (1993) Human c-myc transcription factor PuF identified as nm23-H2 nucleoside diphosphate kinase, a candidate suppressor of tumor metastasis. Science 261:478–480. doi:10.1126/science.8392752

    Article  PubMed  CAS  Google Scholar 

  49. Berberich SJ, Postel EH (1995) PuF/NM23-H2/NDPK-B transactivates a human c-myc promoter-CAT gene via a functional nuclease hypersensitive element. Oncogene 10:2343–2347

    PubMed  CAS  Google Scholar 

  50. Agou F, Raveh S, Mesnildrey S, Veron M (1999) Single strand DNA specificity analysis of human nucleoside diphosphate kinase B. J Biol Chem 274:19630–19638. doi:10.1074/jbc.274.28.19630

    Article  PubMed  CAS  Google Scholar 

  51. Raveh S, Vinh J, Rossier J, Agou F, Veron M (2001) Peptidic determinants and structural model of human NDP kinase B (Nm23-H2) bound to single-stranded DNA. Biochemistry 40:5882–5893. doi:10.1021/bi001085j

    Article  PubMed  CAS  Google Scholar 

  52. Cho SJ, Lee NS, Jung YS, Lee H, Lee KJ, Kim E, Chae SK (2001) Identification of structural domains affecting transactivation potential of Nm23. Biochem Biophys Res Commun 289:738–743. doi:10.1006/bbrc.2001.6042

    Article  PubMed  CAS  Google Scholar 

  53. Subramanian C, Cotter MAII, Robertson ES (2001) Epstein–Barr virus nuclear protein EBNA-3C interacts with the human metastatic suppressor Nm23-H1: a molecular link to cancer metastasis. Nat Med 7:350–355. doi:10.1038/85499

    Article  PubMed  CAS  Google Scholar 

  54. Kelly GL, Milner AE, Baldwin GS, Bell AI, Rickinson AB (2006) Three restricted forms of Epstein–Barr virus latency counteracting apoptosis in c-myc-expressing Burkitt lymphoma cells. Proc Natl Acad Sci USA 103:14935–14940. doi:10.1073/pnas.0509988103

    Article  PubMed  CAS  Google Scholar 

  55. Murakami M, Lan K, Subramanian C, Robertson ES (2005) Epstein–Barr virus nuclear antigen 1 interacts with Nm23-H1 in lymphoblastoid cell lines and inhibits its ability to suppress cell migration. J Virol 79:1559–1568. doi:10.1128/JVI.79.3.1559-1568.2005

    Article  PubMed  CAS  Google Scholar 

  56. Wagner PD, Vu ND (2000) Phosphorylation of geranyl and farnesyl pyrophosphates by Nm23 proteins/nucleoside diphosphate kinases. J Biol Chem 275:35570–35576. doi:10.1074/jbc.M006106200

    Article  PubMed  CAS  Google Scholar 

  57. Wagner PD, Vu ND (2000) Histidine to aspartate phosphotransferase activity of nm23 proteins: phosphorylation of aldolase C on Asp-319. Biochem J 346(Pt 3):623–630. doi:10.1042/0264-6021:3460623

    Article  PubMed  CAS  Google Scholar 

  58. Hartsough MT, Morrison DK, Salerno M, Palmieri D, Ouatas T, Mair M, Patrick J, Steeg PS (2002) Nm23-H1 metastasis suppressor phosphorylation of kinase suppressor of Ras via a histidine protein kinase pathway. J Biol Chem 277:32389–32399. doi:10.1074/jbc.M203115200

    Article  PubMed  CAS  Google Scholar 

  59. Flemington EK (2001) Herpesvirus lytic replication and the cell cycle: arresting new developments. J Virol 75:4475–4481. doi:10.1128/JVI.75.10.4475-4481.2001

    Article  PubMed  CAS  Google Scholar 

  60. Parker GA, Crook T, Bain M, Sara EA, Farrell PJ, Allday MJ (1996) Epstein–Barr virus nuclear antigen (EBNA)3C is an immortalizing oncoprotein with similar properties to adenovirus E1A and papillomavirus E7. Oncogene 13:2541–2549

    PubMed  CAS  Google Scholar 

  61. Maruo S, Wu Y, Ishikawa S, Kanda T, Iwakiri D, Takada K (2006) Epstein–Barr virus nuclear protein EBNA3C is required for cell cycle progression and growth maintenance of lymphoblastoid cells. Proc Natl Acad Sci USA 103:19500–19505. doi:10.1073/pnas.0604919104

    Article  PubMed  CAS  Google Scholar 

  62. Knight JS, Sharma N, Robertson ES (2005) Epstein–Barr virus latent antigen 3C can mediate the degradation of the retinoblastoma protein through an SCF cellular ubiquitin ligase. Proc Natl Acad Sci USA 102:18562–18566. doi:10.1073/pnas.0503886102

    Article  PubMed  CAS  Google Scholar 

  63. Knight JS, Sharma N, Robertson ES (2005) SCFSkp2 complex targeted by Epstein–Barr virus essential nuclear antigen. Mol Cell Biol 25:1749–1763. doi:10.1128/MCB.25.5.1749-1763.2005

    Article  PubMed  CAS  Google Scholar 

  64. Parker GA, Touitou R, Allday MJ (2000) Epstein–Barr virus EBNA3C can disrupt multiple cell cycle checkpoints and induce nuclear division divorced from cytokinesis. Oncogene 19:700–709. doi:10.1038/sj.onc.1203327

    Article  PubMed  CAS  Google Scholar 

  65. Andres V (2004) Control of vascular cell proliferation and migration by cyclin-dependent kinase signalling: new perspectives and therapeutic potential. Cardiovasc Res 63:11–21. doi:10.1016/j.cardiores.2004.02.009

    Article  PubMed  CAS  Google Scholar 

  66. Knight JS, Robertson ES (2004) Epstein–Barr virus nuclear antigen 3C regulates cyclin A/p27 complexes and enhances cyclin A-dependent kinase activity. J Virol 78:1981–1991. doi:10.1128/JVI.78.4.1981-1991.2004

    Article  PubMed  CAS  Google Scholar 

  67. Knight JS, Sharma N, Kalman DE, Robertson ES (2004) A cyclin-binding motif within the amino-terminal homology domain of EBNA3C binds cyclin A and modulates cyclin A-dependent kinase activity in Epstein–Barr virus-infected cells. J Virol 78:12857–12867. doi:10.1128/JVI.78.23.12857-12867.2004

    Article  PubMed  CAS  Google Scholar 

  68. Krauer KG, Burgess A, Buck M, Flanagan J, Sculley TB, Gabrielli B (2004) The EBNA-3 gene family proteins disrupt the G2/M checkpoint. Oncogene 23:1342–1353. doi:10.1038/sj.onc.1207253

    Article  PubMed  CAS  Google Scholar 

  69. Choudhuri T, Verma SC, Lan K, Murakami M, Robertson ES (2007) The ATM/ATR signaling effector Chk2 is targeted by Epstein–Barr virus nuclear antigen 3C to release the G2/M cell cycle block. J Virol 81:6718–6730. doi:10.1128/JVI.00053-07

    Article  PubMed  CAS  Google Scholar 

  70. Jung H, Seong HA, Ha H (2007) NM23-H1 tumor suppressor and its interacting partner STRAP activate p53 function. J Biol Chem 282:35293–35307. doi:10.1074/jbc.M705181200

    Article  PubMed  CAS  Google Scholar 

  71. Kuppers DA, Lan K, Knight JS, Robertson ES (2005) Regulation of matrix metalloproteinase 9 expression by Epstein–Barr virus nuclear antigen 3C and the suppressor of metastasis Nm23-H1. J Virol 79:9714–9724. doi:10.1128/JVI.79.15.9714-9724.2005

    Article  PubMed  CAS  Google Scholar 

  72. Choudhuri T, Verma SC, Lan K, Robertson ES (2006) Expression of alpha V integrin is modulated by Epstein–Barr virus nuclear antigen 3C and the metastasis suppressor Nm23-H1 through interaction with the GATA-1 and Sp1 transcription factors. Virology 351:58–72. doi:10.1016/j.virol.2006.03.031

    Article  PubMed  CAS  Google Scholar 

  73. Stamenkovic I (2000) Matrix metalloproteinases in tumor invasion and metastasis. Semin Cancer Biol 10:415–433. doi:10.1006/scbi.2000.0379

    Article  PubMed  CAS  Google Scholar 

  74. Westermarck J, Kahari VM (1999) Regulation of matrix metalloproteinase expression in tumor invasion. FASEB J 13:781–792

    PubMed  CAS  Google Scholar 

  75. Deryugina EI, Quigley JP (2006) Matrix metalloproteinases and tumor metastasis. Cancer Metastasis Rev 25:9–34. doi:10.1007/s10555-006-7886-9

    Article  PubMed  CAS  Google Scholar 

  76. Nemeth JA, Nakada MT, Trikha M, Lang Z, Gordon MS, Jayson GC, Corringham R, Prabhakar U, Davis HM, Beckman RA (2007) Alpha-v integrins as therapeutic targets in oncology. Cancer Invest 25:632–646. doi:10.1080/07357900701522638

    Article  PubMed  CAS  Google Scholar 

  77. Huang S, Stupack D, Liu A, Cheresh D, Nemerow GR (2000) Cell growth and matrix invasion of EBV-immortalized human B lymphocytes is regulated by expression of alpha(v) integrins. Oncogene 19:1915–1923. doi:10.1038/sj.onc.1203509

    Article  PubMed  CAS  Google Scholar 

  78. Trocme C, Gaudin P, Berthier S, Barro C, Zaoui P, Morel F (1998) Human B lymphocytes synthesize the 92-kDa gelatinase, matrix metalloproteinase-9. J Biol Chem 273:20677–20684. doi:10.1074/jbc.273.32.20677

    Article  PubMed  CAS  Google Scholar 

  79. Yoshizaki T, Sato H, Furukawa M, Pagano JS (1998) The expression of matrix metalloproteinase 9 is enhanced by Epstein–Barr virus latent membrane protein 1. Proc Natl Acad Sci USA 95:3621–3626. doi:10.1073/pnas.95.7.3621

    Article  PubMed  CAS  Google Scholar 

  80. Lombardi D (2006) Commentary: nm23, a metastasis suppressor gene with a tumor suppressor gene aptitude? J Bioenerg Biomembr 38:177–180. doi:10.1007/s10863-006-9032-3

    Article  PubMed  CAS  Google Scholar 

  81. Steeg PS, Ouatas T, Halverson D, Palmieri D, Salerno M (2003) Metastasis suppressor genes: basic biology and potential clinical use. Clin Breast Cancer 4:51–62. doi:10.3816/CBC.2003.n.012

    Article  PubMed  CAS  Google Scholar 

  82. Kaul R, Verma SC, Murakami M, Lan K, Choudhuri T, Robertson ES (2006) Epstein–Barr virus protein can upregulate cyclo-oxygenase-2 expression through association with the suppressor of metastasis Nm23-H1. J Virol 80:1321–1331. doi:10.1128/JVI.80.3.1321-1331.2006

    Article  PubMed  CAS  Google Scholar 

  83. Tseng YH, Vicent D, Zhu J, Niu Y, Adeyinka A, Moyers JS, Watson PH, Kahn CR (2001) Regulation of growth and tumorigenicity of breast cancer cells by the low molecular weight GTPase Rad and nm23. Cancer Res 61:2071–2079

    PubMed  CAS  Google Scholar 

  84. Engel M, Issinger OG, Lascu I, Seib T, Dooley S, Zang KD, Welter C (1994) Phosphorylation of nm23/nucleoside diphosphate kinase by casein kinase 2 in vitro. Biochem Biophys Res Commun 199:1041–1048. doi:10.1006/bbrc.1994.1334

    Article  PubMed  CAS  Google Scholar 

  85. Biondi RM, Engel M, Sauane M, Welter C, Issinger OG, Jimenez de Asua L, Passeron S (1996) Inhibition of nucleoside diphosphate kinase activity by in vitro phosphorylation by protein kinase CK2. Differential phosphorylation of NDP kinases in HeLa cells in culture. FEBS Lett 399:183–187. doi:10.1016/S0014-5793(96)01299-9

    Article  PubMed  CAS  Google Scholar 

  86. Garzia L, D’Angelo A, Amoresano A, Knauer SK, Cirulli C, Campanella C, Stauber RH, Steegborn C, Iolascon A, Zollo M (2008) Phosphorylation of nm23-H1 by CKI induces its complex formation with h-prune and promotes cell motility. Oncogene 27:1853–1864. doi:10.1038/sj.onc.1210822

    Article  PubMed  CAS  Google Scholar 

  87. Marino N, Zollo M (2007) Understanding h-prune biology in the fight against cancer. Clin Exp Metastasis 24:637–645. doi:10.1007/s10585-007-9109-3

    Article  PubMed  CAS  Google Scholar 

  88. D’Angelo A, Garzia L, Andre A, Carotenuto P, Aglio V, Guardiola O, Arrigoni G, Cossu A, Palmieri G, Aravind L, Zollo M (2004) Prune cAMP phosphodiesterase binds nm23-H1 and promotes cancer metastasis. Cancer Cell 5:137–149. doi:10.1016/S1535-6108(04)00021-2

    Article  PubMed  Google Scholar 

  89. Fan Z, Beresford PJ, Oh DY, Zhang D, Lieberman J (2003) Tumor suppressor NM23-H1 is a granzyme A-activated DNase during CTL-mediated apoptosis, and the nucleosome assembly protein SET is its inhibitor. Cell 112:659–672. doi:10.1016/S0092-8674(03)00150-8

    Article  PubMed  CAS  Google Scholar 

  90. Bornkamm GW, Hammerschmidt W (2001) Molecular virology of Epstein–Barr virus. Philos Trans R Soc Lond B Biol Sci 356:437–459. doi:10.1098/rstb.2000.0781

    Article  PubMed  CAS  Google Scholar 

  91. Murono S, Inoue H, Tanabe T, Joab I, Yoshizaki T, Furukawa M, Pagano JS (2001) Induction of cyclooxygenase-2 by Epstein–Barr virus latent membrane protein 1 is involved in vascular endothelial growth factor production in nasopharyngeal carcinoma cells. Proc Natl Acad Sci USA 98:6905–6910. doi:10.1073/pnas.121016998

    Article  PubMed  CAS  Google Scholar 

  92. Sano H, Kawahito Y, Wilder RL, Hashiramoto A, Mukai S, Asai K, Kimura S, Kato H, Kondo M, Hla T (1995) Expression of cyclooxygenase-1 and -2 in human colorectal cancer. Cancer Res 55:3785–3789

    PubMed  CAS  Google Scholar 

  93. Wolff H, Saukkonen K, Anttila S, Karjalainen A, Vainio H, Ristimaki A (1998) Expression of cyclooxygenase-2 in human lung carcinoma. Cancer Res 58:4997–5001

    PubMed  CAS  Google Scholar 

  94. Hwang D, Scollard D, Byrne J, Levine E (1998) Expression of cyclooxygenase-1 and cyclooxygenase-2 in human breast cancer. J Natl Cancer Inst 90:455–460. doi:10.1093/jnci/90.6.455

    Article  PubMed  CAS  Google Scholar 

  95. Ristimaki A, Honkanen N, Jankala H, Sipponen P, Harkonen M (1997) Expression of cyclooxygenase-2 in human gastric carcinoma. Cancer Res 57:1276–1280

    PubMed  CAS  Google Scholar 

  96. Zimmermann KC, Sarbia M, Weber AA, Borchard F, Gabbert HE, Schror K (1999) Cyclooxygenase-2 expression in human esophageal carcinoma. Cancer Res 59:198–204

    PubMed  CAS  Google Scholar 

  97. Tang DW, Lin SC, Chang KW, Chi CW, Chang CS, Liu TY (2003) Elevated expression of cyclooxygenase (COX)-2 in oral squamous cell carcinoma—evidence for COX-2 induction by areca quid ingredients in oral keratinocytes. J Oral Pathol Med 32:522–529. doi:10.1034/j.1600-0714.2003.00182.x

    Article  PubMed  CAS  Google Scholar 

  98. Sheng H, Shao J, Kirkland SC, Isakson P, Coffey RJ, Morrow J, Beauchamp RD, DuBois RN (1997) Inhibition of human colon cancer cell growth by selective inhibition of cyclooxygenase-2. J Clin Invest 99:2254–2259. doi:10.1172/JCI119400

    Article  PubMed  CAS  Google Scholar 

  99. Rioux N, Castonguay A (1998) Prevention of NNK-induced lung tumorigenesis in A/J mice by acetylsalicylic acid and NS-398. Cancer Res 58:5354–5360

    PubMed  CAS  Google Scholar 

  100. Reddy BS (2000) The fourth DeWitt S. Goodman lecture. Novel approaches to the prevention of colon cancer by nutritional manipulation and chemoprevention. Cancer Epidemiol Biomarkers Prev 9:239–247

    PubMed  CAS  Google Scholar 

  101. Sawaoka H, Kawano S, Tsuji S, Tsujii M, Gunawan ES, Takei Y, Nagano K, Hori M (1998) Cyclooxygenase-2 inhibitors suppress the growth of gastric cancer xenografts via induction of apoptosis in nude mice. Am J Physiol 274:G1061–G1067

    PubMed  CAS  Google Scholar 

  102. Molina MA, Sitja-Arnau M, Lemoine MG, Frazier ML, Sinicrope FA (1999) Increased cyclooxygenase-2 expression in human pancreatic carcinomas and cell lines: growth inhibition by nonsteroidal anti-inflammatory drugs. Cancer Res 59:4356–4362

    PubMed  CAS  Google Scholar 

  103. Peng JP, Chang HC, Hwang CF, Hung WC (2005) Overexpression of cyclooxygenase-2 in nasopharyngeal carcinoma and association with lymph node metastasis. Oral Oncol 41:903–908. doi:10.1016/j.oraloncology.2005.05.003

    Article  PubMed  CAS  Google Scholar 

  104. Smith WL, DeWitt DL, Garavito RM (2000) Cyclooxygenases: structural, cellular, and molecular biology. Annu Rev Biochem 69:145–182. doi:10.1146/annurev.biochem.69.1.145

    Article  PubMed  CAS  Google Scholar 

  105. Smith WL, Garavito RM, DeWitt DL (1996) Prostaglandin endoperoxide H synthases (cyclooxygenases)-1 and -2. J Biol Chem 271:33157–33160. doi:10.1074/jbc.271.52.33157

    Article  PubMed  CAS  Google Scholar 

  106. Needleman P, Turk J, Jakschik BA, Morrison AR, Lefkowith JB (1986) Arachidonic acid metabolism. Annu Rev Biochem 55:69–102. doi:10.1146/annurev.bi.55.070186.000441

    Article  PubMed  CAS  Google Scholar 

  107. Herschman HR (1996) Prostaglandin synthase 2. Biochim Biophys Acta 1299:125–140

    PubMed  Google Scholar 

  108. Levy GN (1997) Prostaglandin H synthases, nonsteroidal anti-inflammatory drugs, and colon cancer. FASEB J 11:234–247

    PubMed  CAS  Google Scholar 

  109. Ray N, Bisher ME, Enquist LW (2004) Cyclooxygenase-1 and -2 are required for production of infectious pseudorabies virus. J Virol 78:12964–12974. doi:10.1128/JVI.78.23.12964-12974.2004

    Article  PubMed  CAS  Google Scholar 

  110. Hansen SG, Strelow LI, Franchi DC, Anders DG, Wong SW (2003) Complete sequence and genomic analysis of rhesus cytomegalovirus. J Virol 77:6620–6636. doi:10.1128/JVI.77.12.6620-6636.2003

    Article  PubMed  CAS  Google Scholar 

  111. Symensma TL, Martinez-Guzman D, Jia Q, Bortz E, Wu TT, Rudra-Ganguly N, Cole S, Herschman H, Sun R (2003) COX-2 induction during murine gammaherpesvirus 68 infection leads to enhancement of viral gene expression. J Virol 77:12753–12763. doi:10.1128/JVI.77.23.12753-12763.2003

    Article  PubMed  CAS  Google Scholar 

  112. Sharma-Walia N, Raghu H, Sadagopan S, Sivakumar R, Veettil MV, Naranatt PP, Smith MM, Chandran B (2006) Cyclooxygenase 2 induced by Kaposi’s sarcoma-associated herpesvirus early during in vitro infection of target cells plays a role in the maintenance of latent viral gene expression. J Virol 80:6534–6552. doi:10.1128/JVI.00231-06

    Article  PubMed  CAS  Google Scholar 

  113. Narumiya S, Sugimoto Y, Ushikubi F (1999) Prostanoid receptors: structures, properties, and functions. Physiol Rev 79:1193–1226

    PubMed  CAS  Google Scholar 

  114. Ye J, Gradoville L, Daigle D, Miller G (2007) De novo protein synthesis is required for lytic cycle reactivation of Epstein–Barr virus, but not Kaposi’s sarcoma-associated herpesvirus, in response to histone deacetylase inhibitors and protein kinase C agonists. J Virol 81:9279–9291. doi:10.1128/JVI.00982-07

    Article  PubMed  CAS  Google Scholar 

  115. Gebhardt BM, Varnell ED, Kaufman HE (2005) Inhibition of cyclooxygenase 2 synthesis suppresses Herpes simplex virus type 1 reactivation. J Ocul Pharmacol Ther 21:114–120. doi:10.1089/jop.2005.21.114

    Article  PubMed  CAS  Google Scholar 

  116. Askling J, Klareskog L, Blomqvist P, Fored M, Feltelius N (2006) Risk for malignant lymphoma in ankylosing spondylitis: a nationwide Swedish case-control study. Ann Rheum Dis 65:1184–1187. doi:10.1136/ard.2005.047514

    Article  PubMed  CAS  Google Scholar 

  117. Wolfe F, Michaud K (2004) Lymphoma in rheumatoid arthritis: the effect of methotrexate and anti-tumor necrosis factor therapy in 18, 572 patients. Arthritis Rheum 50:1740–1751. doi:10.1002/art.20311

    Article  PubMed  CAS  Google Scholar 

  118. Murakami M, Meneses PI, Knight JS, Lan K, Kaul R, Verma SC, Robertson ES (2008) Nm23–H1 modulates the activity of the guanine exchange factor Dbl-1. Int J Cancer 123:500–510

    Article  PubMed  CAS  Google Scholar 

  119. Murakami M, Meneses PI, Knight JS, Lan K, Kaul R, Verma SC, Robertson ES (2008) The suppressor of metastasis Nm23-H1 interacts with the Cdc42 Rho family member and the pleckstrin homology domain of oncoprotein Dbl-1 to suppress cell migration. Cancer Biol Ther 7:679–690. doi:10.1158/1535-7163.MCT-07-0450

    Article  CAS  Google Scholar 

  120. Mileo AM, Piombino E, Severino A, Tritarelli A, Paggi MG, Lombardi D (2006) Multiple interference of the human papillomavirus-16 E7 oncoprotein with the functional role of the metastasis suppressor Nm23-H1 protein. J Bioenerg Biomembr 38:215–225. doi:10.1007/s10863-006-9037-y

    Article  PubMed  CAS  Google Scholar 

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  1. Department of Microbiology and Tumor Virology Program of Abramson Comprehensive Cancer Center, University of Pennsylvania School of Medicine, 201E Johnson Pavilion, 3610 Hamilton Walk, Philadelphia, PA, 19104, USA

    Masanao Murakami, Rajeev Kaul, Pankaj Kumar & Erle S. Robertson

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  1. Masanao Murakami
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Murakami, M., Kaul, R., Kumar, P. et al. Nucleoside diphosphate kinase/Nm23 and Epstein–Barr virus. Mol Cell Biochem 329, 131–139 (2009). https://doi.org/10.1007/s11010-009-0123-4

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