PL EN


Preferencje help
Widoczny [Schowaj] Abstrakt
Liczba wyników
2009 | 14 | 2 |

Tytuł artykułu

The signaling pathways of Epstein-Barr virus-encoded latent membrane protein 2A [LMP2A] in latency and cancer

Warianty tytułu

Języki publikacji

EN

Abstrakty

EN
Epstein-Barr virus (EBV) is a ubiquitous virus with infections commonly resulting in a latency carrier state. Although the exact role of EBV in cancer pathogenesis remains not entirely clear, it is highly probable that it causes several lymphoid and epithelial malignancies, such as Hodgkin’s lymphoma, NK-T cell lymphoma, Burkitt’s lymphoma, and nasopharyngeal carcinoma. EBV-associated malignancies are associated with a latent form of infection, and several of these EBV-encoded latent proteins are known to mediate cellular transformation. These include six nuclear antigens and three latent membrane proteins. Studies have shown that EBV displays distinct patterns of viral latent gene expression in these lymphoid and epithelial tumors. The constant expression of latent membrane protein 2A (LMP2A) at the RNA level in both primary and metastatic tumors suggests that this protein might be a driving factor in the tumorigenesis of EBV-associated malignancies. LMP2A may cooperate with the aberrant host genome, and thereby contribute to malignant transformation by intervening in signaling pathways at multiple points, especially in the cell cycle and apoptotic pathway. This review summarizes the role of EBV-encoded LMP2A in EBV-associated viral latency and cancers. We will focus our discussions on the molecular interactions of each of the conserved motifs in LMP2A, and their involvement in various signaling pathways, namely the B-cell receptor blockade mechanism, the ubiquitin-mediated (Notch and Wnt) pathways, and the MAPK, PI3-K/Akt, NK-κB and STAT pathways, which can provide us with important insights into the roles of LMP2A in the EBV-associated latency state and various malignancies.

Wydawca

-

Rocznik

Tom

14

Numer

2

Opis fizyczny

p.222-247,fig.,ref.

Twórcy

autor
  • Karolinska Institute, Stockholm, Sweden
autor
autor

Bibliografia

  • 1. Masucci, M.G. and Ernberg, I. Epstein-Barr virus: adaptation to a life within the immune system. Trends Microbiol. 2 (1994) 125-130.
  • 2. Junker, A.K. Epstein-Barr virus. Pediatr. Rev. 26 (2005) 79-85.
  • 3. Schuster, V. and Kreth, H.W. Epstein-Barr virus infection and associated diseases in children. II. Diagnostic and therapeutic strategies. Eur. J. Pediatr. 151 (1992) 794-798.
  • 4. Schuster, V. and Kreth, H.W. Epstein-Barr virus infection and associated diseases in children. I. Pathogenesis, epidemiology and clinical aspects. Eur. J. Pediatr. 151 (1992) 718-725.
  • 5. Epstein, M.A., Achong, B.G., Barr, Y.M., Zajac, B., Henle, G. and Henle, W. Morphological and virological investigations on cultured Burkitt tumor lymphoblasts (strain Raji). J. Natl. Cancer Inst. 37 (1966) 547-559.
  • 6. Henle, G., Henle, W. and Diehl, V. Relation of Burkitt's tumor-associated herpes-ytpe virus to infectious mononucleosis. Proc. Natl. Acad. Sci. USA 59 (1968) 94-101.
  • 7. Weiss, L.M., Movahed, L.A., Warnke, R.A. and Sklar, J. Detection of Epstein-Barr viral genomes in Reed-Sternberg cells of Hodgkin's disease. N. Engl. J. Med. 320 (1989) 502-506.
  • 8. Weiss, L.M., Jaffe, E.S., Liu, X.F., Chen, Y.Y., Shibata, D. and Medeiros, L.J. Detection and localization of Epstein-Barr viral genomes in angioimmunoblastic lymphadenopathy and angioimmunoblastic lymphadenopathy-like lymphoma. Blood 79 (1992) 1789-1795.
  • 9. Jones, J.F., Shurin, S., Abramowsky, C., Tubbs, R.R., Sciotto, C.G., Wahl, R., Sands, J., Gottman, D., Katz, B.Z. and Sklar, J. T-cell lymphomas containing Epstein-Barr viral DNA in patients with chronic Epstein-Barr virus infections. N. Engl. J. Med. 318 (1988) 733-741.
  • 10. Gunven, P., Klein, G., Henle, G., Henle, W. and Clifford, P. Epstein-Barr virus in Burkitt's lymphoma and nasopharyngeal carcinoma. Antibodies to EBV associated membrane and viral capsid antigens in Burkitt lymphoma patients. Nature 228 (1970) 1053-1056.
  • 11. Bonnet, M., Guinebretiere, J.M., Kremmer, E., Grunewald, V., Benhamou, E., Contesso, G. and Joab, I. Detection of Epstein-Barr virus in invasive breast cancers. J. Natl. Cancer Inst. 91 (1999) 1376-1381.
  • 12. Glaser, S.L., Ambinder, R.F., DiGiuseppe, J.A., Horn-Ross, P.L. and Hsu, J.L. Absence of Epstein-Barr virus EBER-1 transcripts in an epidemiologically diverse group of breast cancers. Int. J. Cancer 75 (1998) 555-558.
  • 13. Labrecque, L.G., Barnes, D.M., Fentiman, I.S. and Griffin, B.E. EpsteinBarr virus in epithelial cell tumors: a breast cancer study. Cancer Res. 55 (1995) 39-45.
  • 14. Lespagnard, L., Cochaux, P., Larsimont, D., Degeyter, M., Velu, T. and Heimann, R. Absence of Epstein-Barr virus in medullary carcinoma of the breast as demonstrated by immunophenotyping, in situ hybridization and polymerase chain reaction. Am. J. Clin. Pathol. 103 (1995) 449-452.
  • 15. Niedobitek, G., Herbst, H., Young, L.S., Rowe, M., Dienemann, D., Germer, C. and Stein, H. Epstein-Barr virus and carcinomas. Expression of the viral genome in an undifferentiated gastric carcinoma. Diagn. Mol. Pathol. 1 (1992) 103-108.
  • 16. Oda, K., Tamaru, J., Takenouchi, T., Mikata, A., Nunomura, M., Saitoh, N., Sarashina, H. and Nakajima, N. Association of Epstein-Barr virus with gastric carcinoma with lymphoid stroma. Am. J. Pathol. 143 (1993) 1063- 1071.
  • 17. Thompson, M.P. and Kurzrock, R. Epstein-Barr virus and cancer. Clin. Cancer Res. 10 (2004) 803-821.
  • 18. Clemens, M.J., Laing, K.G., Jeffrey, I.W., Schofield, A., Sharp, T.V., Elia, A., Matys, V., James, M.C. and Tilleray, V.J. Regulation of the interferoninducible eIF-2 alpha protein kinase by small RNAs. Biochimie 76 (1994) 770-778.
  • 19. Brooks, L., Yao, Q.Y., Rickinson, A.B. and Young, L.S. Epstein-Barr virus latent gene transcription in nasopharyngeal carcinoma cells: coexpression of EBNA1, LMP1, and LMP2 transcripts. J. Virol. 66 (1992) 2689-2697.
  • 20. Chen, S.Y., Lu, J., Shih, Y.C. and Tsai, C.H. Epstein-Barr virus latent membrane protein 2A regulates c-Jun protein through extracellular signalregulated kinase. J. Virol. 76 (2002) 9556-9561.
  • 21. Deacon, E.M., Pallesen, G., Niedobitek, G., Crocker, J., Brooks, L., Rickinson, A.B. and Young, L.S. Epstein-Barr virus and Hodgkin's disease: transcriptional analysis of virus latency in the malignant cells. J. Exp. Med. 177 (1993) 339-349.
  • 22. Herbst, H., Dallenbach, F., Hummel, M., Niedobitek, G., Pileri, S., MullerLantzsch, N. and Stein, H. Epstein-Barr virus latent membrane protein expression in Hodgkin and Reed-Sternberg cells. Proc. Natl. Acad. Sci. USA 88 (1991) 4766-4770.
  • 23. Murray, P.G., Young, L.S., Rowe, M. and Crocker, J. Immunohistochemical demonstration of the Epstein-Barr virus-encoded latent membrane protein in paraffin sections of Hodgkin's disease. J. Pathol. 166 (1992) 1-5.
  • 24. Rowe, M., Lear, A.L., Croom-Carter, D., Davies, A.H. and Rickinson, A.B. Three pathways of Epstein-Barr virus gene activation from EBNA1-positive latency in B lymphocytes. J. Virol. 66 (1992) 122-131.
  • 25. Babcock, G.J., Hochberg, D. and Thorley-Lawson, A.D. The expression pattern of Epstein-Barr virus latent genes in vivo is dependent upon the differentiation stage of the infected B cell. Immunity 13 (2000) 497-506.
  • 26. Rowe, M., Rowe, D.T., Gregory, C.D., Young, L.S., Farrell, P.J., Rupani, H. and Rickinson, A.B. Differences in B cell growth phenotype reflect novel patterns of Epstein-Barr virus latent gene expression in Burkitt's lymphoma cells. EMBO J. 6 (1987) 2743-2751.
  • 27. Raab-Traub, N. Epstein-Barr virus in the pathogenesis of NPC. Semin. Cancer Biol. 12 (2002) 431-441.
  • 28. Young, L., Alfieri, C., Hennessy, K., Evans, H., O'Hara, C., Anderson, K.C., Ritz, J., Shapiro, R.S., Rickinson, A., Kieff, E. and et al. Expression of Epstein-Barr virus transformation-associated genes in tissues of patients with EBV lymphoproliferative disease. N. Engl. J. Med. 321 (1989) 1080-1085.
  • 29. Tierney, R.J., Steven, N., Young, L.S. and Rickinson, A.B. Epstein-Barr virus latency in blood mononuclear cells: analysis of viral gene transcription during primary infection and in the carrier state. J. Virol. 68 (1994) 7374- 7385.
  • 30. Brink, A.A., Dukers, D.F., van den Brule, A.J., Oudejans, J.J., Middeldorp, J.M., Meijer, C.J. and Jiwa, M. Presence of Epstein-Barr virus latency type III at the single cell level in post-transplantation lymphoproliferative disorders and AIDS related lymphomas. J. Clin. Pathol. 50 (1997) 911-918.
  • 31. Young, L.S. and Murray, P.G. Epstein-Barr virus and oncogenesis: from latent genes to tumours. Oncogene 22 (2003) 5108-5121.
  • 32. Chen, F., Hu, L.F., Ernberg, I., Klein, G. and Winberg, G. Coupled transcription of Epstein-Barr virus latent membrane protein (LMP)-1 and LMP-2B genes in nasopharyngeal carcinomas. J. Gen. Virol. 76 (1995) 131-138.
  • 33. Busson, P., McCoy, R., Sadler, R., Gilligan, K., Tursz, T. and Raab-Traub, N. Consistent transcription of the Epstein-Barr virus LMP2 gene in nasopharyngeal carcinoma. J. Virol. 66 (1992) 3257-3262.
  • 34. Sample, J., Liebowitz, D. and Kieff, E. Two related Epstein-Barr virus membrane proteins are encoded by separate genes. J. Virol. 63 (1989) 933-937.
  • 35. Laux, G., Economou, A. and Farrell, P.J. The terminal protein gene 2 of Epstein-Barr virus is transcribed from a bidirectional latent promoter region. J. Gen. Virol. 70 ( Pt 11) (1989) 3079-3084.
  • 36. Lynch, D.T., Zimmerman, J.S. and Rowe, D.T. Epstein-Barr virus latent membrane protein 2B (LMP2B) co-localizes with LMP2A in perinuclear regions in transiently transfected cells. J. Gen. Virol. 83 (2002) 1025-1035.
  • 37. Rovedo, M. and Longnecker, R. Epstein-barr virus latent membrane protein 2B (LMP2B) modulates LMP2A activity. J. Virol. 81 (2007) 84-94.
  • 38. Brinkmann, M.M. and Schulz, T.F. Regulation of intracellular signalling by the terminal membrane proteins of members of the Gammaherpesvirinae. J. Gen. Virol. 87 (2006) 1047-1074.
  • 39. Fruehling, S., Lee, S.K., Herrold, R., Frech, B., Laux, G., Kremmer, E., Grasser, F.A. and Longnecker, R. Identification of latent membrane protein 2A (LMP2A) domains essential for the LMP2A dominant-negative effect on B-lymphocyte surface immunoglobulin signal transduction. J. Virol. 70 (1996) 6216-6226.
  • 40. Fruehling, S., Swart, R., Dolwick, K.M., Kremmer, E. and Longnecker, R. Tyrosine 112 of latent membrane protein 2A is essential for protein tyrosine kinase loading and regulation of Epstein-Barr virus latency. J. Virol. 72 (1998) 7796-7806.
  • 41. Fruehling, S. and Longnecker, R. The immunoreceptor tyrosine-based activation motif of Epstein-Barr virus LMP2A is essential for blocking BCR-mediated signal transduction. Virology 235 (1997) 241-251.
  • 42. Reth, M. Antigen receptor tail clue. Nature 338 (1989) 383-384.
  • 43. Scholle, F., Longnecker, R. and Raab-Traub, N. Analysis of the phosphorylation status of Epstein-Barr virus LMP2A in epithelial cells. Virology 291 (2001) 208-214.
  • 44. Miller, C.L., Burkhardt, A.L., Lee, J.H., Stealey, B., Longnecker, R., Bolen, J.B. and Kieff, E. Integral membrane protein 2 of Epstein-Barr virus regulates reactivation from latency through dominant negative effects on protein-tyrosine kinases. Immunity 2 (1995) 155-166.
  • 45. Swart, R., Fruehling, S. and Longnecker, R. Tyrosines 60, 64, and 101 of Epstein-Barr virus LMP2A are not essential for blocking B cell signal transduction. Virology 263 (1999) 485-495.
  • 46. Busson, P., Edwards, R.H., Tursz, T. and Raab-Traub, N. Sequence polymorphism in the Epstein-Barr virus latent membrane protein (LMP)-2 gene. J. Gen. Virol. 76 (1995) 139-145.
  • 47. Franken, M., Annis, B., Ali, A.N. and Wang, F. 5' Coding and regulatory region sequence divergence with conserved function of the Epstein-Barr virus LMP2A homolog in herpesvirus papio. J. Virol. 69 (1995) 8011-8019.
  • 48. Feng, S., Chen, J.K., Yu, H., Simon, J.A. and Schreiber, S.L. Two binding orientations for peptides to the Src SH3 domain: development of a general model for SH3-ligand interactions. Science 266 (1994) 1241-1247.
  • 49. Ikeda, A., Merchant, M., Lev, L., Longnecker, R. and Ikeda, M. Latent membrane protein 2A, a viral B cell receptor homologue, induces CD5+ B-1 cell development. J. Immunol. 172 (2004) 5329-5337.
  • 50. Lim, W.A. and Richards, F.M. Critical residues in an SH3 domain from Sem-5 suggest a mechanism for proline-rich peptide recognition. Nat. Struct. Biol. 1 (1994) 221-225.
  • 51. Sudol, M. The WW module competes with the SH3 domain? Trends Biochem. Sci. 21 (1996) 161-163.
  • 52. Sudol, M. Structure and function of the WW domain. Prog. Biophys. Mol. Biol. 65 (1996) 113-132.
  • 53. Longnecker, R. Epstein-Barr virus latency: LMP2, a regulator or means for Epstein-Barr virus persistence? Adv. Cancer Res. 79 (2000) 175-200.
  • 54. Ikeda, M., Ikeda, A., Longan, L.C. and Longnecker, R. The Epstein-Barr virus latent membrane protein 2A PY motif recruits WW domain-containing ubiquitin-protein ligases. Virology 268 (2000) 178-191.
  • 55. Seo, M.D., Park, S.J., Kim, H.J. and Lee, B.J. Identification of the WW domain-interaction sites in the unstructured N-terminal domain of EBV LMP 2A. FEBS Lett. 581 (2007) 65-70.
  • 56. Portis, T. and Longnecker, R. Epstein-Barr virus (EBV) LMP2A mediates B-lymphocyte survival through constitutive activation of the Ras/PI3K/Akt pathway. Oncogene 23 (2004) 8619-8628.
  • 57. Winberg, G., Matskova, L., Chen, F., Plant, P., Rotin, D., Gish, G., Ingham, R., Ernberg, I. and Pawson, T. Latent membrane protein 2A of Epstein-Barr virus binds WW domain E3 protein-ubiquitin ligases that ubiquitinate B-cell tyrosine kinases. Mol. Cell. Biol. 20 (2000) 8526-8535.
  • 58. Portis, T. and Longnecker, R. Epstein-Barr virus LMP2A interferes with global transcription factor regulation when expressed during B-lymphocyte development. J. Virol. 77 (2003) 105-114.
  • 59. Portis, T., Ikeda, M. and Longnecker, R. Epstein-Barr virus LMP2A: regulating cellular ubiquitination processes for maintenance of viral latency? Trends Immunol. 25 (2004) 422-426.
  • 60. Panousis, C.G. and Rowe, D.T. Epstein-Barr virus latent membrane protein 2 associates with and is a substrate for mitogen-activated protein kinase. J. Virol. 71 (1997) 4752-4760.
  • 61. Katzman, R.B. and Longnecker, R. LMP2A does not require palmitoylation to localize to buoyant complexes or for function. J. Virol. 78 (2004) 10878- 10887.
  • 62. Matskova, L., Ernberg, I., Pawson, T. and Winberg, G. C-terminal domain of the Epstein-Barr virus LMP2A membrane protein contains a clustering signal. J. Virol. 75 (2001) 10941-10949.
  • 63. Higuchi, M., Izumi, K.M. and Kieff, E. Epstein-Barr virus latent-infection membrane proteins are palmitoylated and raft-associated: protein 1 binds to the cytoskeleton through TNF receptor cytoplasmic factors. Proc. Natl. Acad. Sci. USA 98 (2001) 4675-4680.
  • 64. Longnecker, R., Miller, C.L., Miao, X.Q., Tomkinson, B. and Kieff, E. The last seven transmembrane and carboxy-terminal cytoplasmic domains of Epstein-Barr virus latent membrane protein 2 (LMP2) are dispensable for lymphocyte infection and growth transformation in vitro. J. Virol. 67 (1993) 2006-2013.
  • 65. Longnecker, R., Miller, C.L., Tomkinson, B., Miao, X.Q. and Kieff, E. Deletion of DNA encoding the first five transmembrane domains of EpsteinBarr virus latent membrane proteins 2A and 2B. J. Virol. 67 (1993) 5068- 5074.
  • 66. Bijlmakers, M.J. and Marsh, M. The on-off story of protein palmitoylation. Trends Cell Biol. 13 (2003) 32-42.
  • 67. Portis, T., Cooper, L., Dennis, P. and Longnecker, R. The LMP2A signalosome--a therapeutic target for Epstein-Barr virus latency and associated disease. Front. Biosci. 7 (2002) d414-426.
  • 68. Miller, C.L., Lee, J.H., Kieff, E., Burkhardt, A.L., Bolen, J.B. and Longnecker, R. Epstein-Barr virus protein LMP2A regulates reactivation from latency by negatively regulating tyrosine kinases involved in sIgmediated signal transduction. Infect. Agents Dis. 3 (1994) 128-136.
  • 69. Miller, C.L., Lee, J.H., Kieff, E. and Longnecker, R. An integral membrane protein (LMP2) blocks reactivation of Epstein-Barr virus from latency following surface immunoglobulin crosslinking. Proc. Natl. Acad. Sci. USA 91 (1994) 772-776.
  • 70. Miller, C.L., Longnecker, R. and Kieff, E. Epstein-Barr virus latent membrane protein 2A blocks calcium mobilization in B lymphocytes. J. Virol. 67 (1993) 3087-3094.
  • 71. Heussinger, N., Buttner, M., Ott, G., Brachtel, E., Pilch, B.Z., Kremmer, E. and Niedobitek, G. Expression of the Epstein-Barr virus (EBV)-encoded latent membrane protein 2A (LMP2A) in EBV-associated nasopharyngeal carcinoma. J. Pathol. 203 (2004) 696-699.
  • 72. Frech, B., Zimber-Strobl, U., Suentzenich, K.O., Pavlish, O., Lenoir, G.M., Bornkamm, G.W. and Mueller-Lantzsch, N. Identification of Epstein-Barr virus terminal protein 1 (TP1) in extracts of four lymphoid cell lines, expression in insect cells, and detection of antibodies in human sera. J. Virol. 64 (1990) 2759-2767.
  • 73. Niedobitek, G., Agathanggelou, A., Herbst, H., Whitehead, L., Wright, D.H. and Young, L.S. Epstein-Barr virus (EBV) infection in infectious mononucleosis: virus latency, replication and phenotype of EBV-infected cells. J. Pathol. 182 (1997) 151-159.
  • 74. Murray, P.G. and Young, L.S. The Role of the Epstein-Barr virus in human disease. Front. Biosci. 7 (2002) d519-540.
  • 75. Longan, L. and Longnecker, R. Epstein-Barr virus latent membrane protein 2A has no growth-altering effects when expressed in differentiating epithelia. J. Gen. Virol. 81 (2000) 2245-2252.
  • 76. Scholle, F., Bendt, K.M. and Raab-Traub, N. Epstein-Barr virus LMP2A transforms epithelial cells, inhibits cell differentiation, and activates Akt. J. Virol. 74 (2000) 10681-10689.
  • 77. Mancao, C. and Hammerschmidt, W. Epstein-Barr virus latent membrane protein 2A is a B-cell receptor mimic and essential for B-cell survival. Blood 110 (2007) 3715-3721.
  • 78. Rowe, D.T. Epstein-Barr virus immortalization and latency. Front. Biosci. 4 (1999) D346-371.
  • 79. Cambier, J.C., Pleiman, C.M. and Clark, M.R. Signal transduction by the B cell antigen receptor and its coreceptors. Annu. Rev. Immunol. 12 (1994) 457-486.
  • 80. Rajewsky, K. Clonal selection and learning in the antibody system. Nature 381 (1996) 751-758.
  • 81. Beaufils, P., Choquet, D., Mamoun, R.Z. and Malissen, B. The (YXXL/I)2 signalling motif found in the cytoplasmic segments of the bovine leukaemia virus envelope protein and Epstein-Barr virus latent membrane protein 2A can elicit early and late lymphocyte activation events. EMBO J. 12 (1993) 5105-5112.
  • 82. Burkhardt, A.L., Bolen, J.B., Kieff, E. and Longnecker, R. An Epstein-Barr virus transformation-associated membrane protein interacts with src family tyrosine kinases. J. Virol. 66 (1992) 5161-5167.
  • 83. Brown, K.D., Hostager, B.S. and Bishop, G.A. Differential signaling and tumor necrosis factor receptor-associated factor (TRAF) degradation mediated by CD40 and the Epstein-Barr virus oncoprotein latent membrane protein 1 (LMP1). J. Exp. Med. 193 (2001) 943-954.
  • 84. Simons, K. and Toomre, D. Lipid rafts and signal transduction. Nat. Rev. Mol. Cell. Biol. 1 (2000) 31-39.
  • 85. Dykstra, M.L., Longnecker, R. and Pierce, S.K. Epstein-Barr virus coopts lipid rafts to block the signaling and antigen transport functions of the BCR. Immunity 14 (2001) 57-67.
  • 86. Caldwell, R.G., Brown, R.C. and Longnecker, R. Epstein-Barr virus LMP2A-induced B-cell survival in two unique classes of EmuLMP2A transgenic mice. J. Virol. 74 (2000) 1101-1113.
  • 87. Casola, S., Otipoby, K.L., Alimzhanov, M., Humme, S., Uyttersprot, N., Kutok, J.L., Carroll, M.C. and Rajewsky, K. B cell receptor signal strength determines B cell fate. Nat. Immunol. 5 (2004) 317-327.
  • 88. Longnecker, R., Druker, B., Roberts, T.M. and Kieff, E. An Epstein-Barr virus protein associated with cell growth transformation interacts with a tyrosine kinase. J. Virol. 65 (1991) 3681-3692.
  • 89. Longnecker, R. and Kieff, E. A second Epstein-Barr virus membrane protein (LMP2) is expressed in latent infection and colocalizes with LMP1. J. Virol. 64 (1990) 2319-2326.
  • 90. Cheng, P.C., Dykstra, M.L., Mitchell, R.N. and Pierce, S.K. A role for lipid rafts in B cell antigen receptor signaling and antigen targeting. J. Exp. Med. 190 (1999) 1549-1560.
  • 91. Simons, K. and Ikonen, E. Functional rafts in cell membranes. Nature 387 (1997) 569-572.
  • 92. Caldwell, R.G., Wilson, J.B., Anderson, S.J. and Longnecker, R. EpsteinBarr virus LMP2A drives B cell development and survival in the absence of normal B cell receptor signals. Immunity 9 (1998) 405-411.
  • 93. Morrison, J.A., Klingelhutz, A.J. and Raab-Traub, N. Epstein-Barr virus latent membrane protein 2A activates beta-catenin signaling in epithelial cells. J. Virol. 77 (2003) 12276-12284.
  • 94. van Noort, M., Meeldijk, J., van der Zee, R., Destree, O. and Clevers, H. Wnt signaling controls the phosphorylation status of beta-catenin. J. Biol. Chem. 277 (2002) 17901-17905.
  • 95. He, Y. and Pear, W.S. Notch signalling in B cells. Semin. Cell Dev. Biol. 14 (2003) 135-142.
  • 96. Maillard, I., He, Y. and Pear, W.S. From the yolk sac to the spleen: New roles for Notch in regulating hematopoiesis. Immunity 18 (2003) 587-589.
  • 97. Jehn, B.M., Dittert, I., Beyer, S., von der Mark, K. and Bielke, W. c-Cbl binding and ubiquitin-dependent lysosomal degradation of membraneassociated Notch1. J. Biol. Chem. 277 (2002) 8033-8040.
  • 98. Lai, E.C. Protein degradation: four E3s for the notch pathway. Curr. Biol. 12 (2002) R74-78.
  • 99. David, M., Petricoin, E., 3rd, Benjamin, C., Pine, R., Weber, M.J. and Larner, A.C. Requirement for MAP kinase (ERK2) activity in interferon alpha- and interferon beta-stimulated gene expression through STAT proteins. Science 269 (1995) 1721-1723.
  • 100.Loeb, D.M., Tsao, H., Cobb, M.H. and Greene, L.A. NGF and other growth factors induce an association between ERK1 and the NGF receptor, gp140prototrk. Neuron 9 (1992) 1053-1065.
  • 101.Morrison, P., Saltiel, A.R. and Rosner, M.R. Role of mitogen-activated protein kinase kinase in regulation of the epidermal growth factor receptor by protein kinase C. J. Biol. Chem. 271 (1996) 12891-12896.
  • 102.Northwood, I.C., Gonzalez, F.A., Wartmann, M., Raden, D.L. and Davis, R.J. Isolation and characterization of two growth factor-stimulated protein kinases that phosphorylate the epidermal growth factor receptor at threonine 669. J. Biol. Chem. 266 (1991) 15266-15276.
  • 103.Vial, E., Sahai, E. and Marshall, C.J. ERK-MAPK signaling coordinately regulates activity of Rac1 and RhoA for tumor cell motility. Cancer Cell 4 (2003) 67-79.
  • 104.Webb, D.J., Donais, K., Whitmore, L.A., Thomas, S.M., Turner, C.E., Parsons, J.T. and Horwitz, A.F. FAK-Src signalling through paxillin, ERK and MLCK regulates adhesion disassembly. Nat. Cell. Biol. 6 (2004) 154-161.
  • 105.Anderson, L.J. and Longnecker, R. EBV LMP2A provides a surrogate pre-B cell receptor signal through constitutive activation of the ERK/MAPK pathway. J. Gen. Virol. 89 (2008) 1563-1568.
  • 106.Angel, P. and Karin, M. The role of Jun, Fos and the AP-1 complex in cellproliferation and transformation. Biochim. Biophys. Acta 1072 (1991) 129-157.
  • 107.Kovary, K. and Bravo, R. The jun and fos protein families are both required for cell cycle progression in fibroblasts. Mol. Cell. Biol. 11 (1991) 4466-4472.
  • 108.Kovary, K. and Bravo, R. Expression of different Jun and Fos proteins during the G0-to-G1 transition in mouse fibroblasts: in vitro and in vivo associations. Mol. Cell. Biol. 11 (1991) 2451-2459.
  • 109.Prochownik, E.V., Smith, M.J., Snyder, K. and Emeagwali, D. Amplified expression of three jun family members inhibits erythroleukemia differentiation. Blood 76 (1990) 1830-1837.
  • 110.Su, H.Y., Bos, T.J., Monteclaro, F.S. and Vogt, P.K. Jun inhibits myogenic differentiation. Oncogene 6 (1991) 1759-1766.
  • 111.Hibi, M., Lin, A., Smeal, T., Minden, A. and Karin, M. Identification of an oncoprotein- and UV-responsive protein kinase that binds and potentiates the c-Jun activation domain. Genes Dev. 7 (1993) 2135-2148.
  • 112.Treier, M., Staszewski, L.M. and Bohmann, D. Ubiquitin-dependent c-Jun degradation in vivo is mediated by the delta domain. Cell 78 (1994) 787-798.
  • 113.Schutte, J., Viallet, J., Nau, M., Segal, S., Fedorko, J. and Minna, J. jun-B inhibits and c-fos stimulates the transforming and trans-activating activities of c-jun. Cell 59 (1989) 987-997.
  • 114.Smeal, T., Binetruy, B., Mercola, D.A., Birrer, M. and Karin, M. Oncogenic and transcriptional cooperation with Ha-Ras requires phosphorylation of c-Jun on serines 63 and 73. Nature 354 (1991) 494-496.
  • 115.Cho, A., Graves, J. and Reidy, M.A. Mitogen-activated protein kinases mediate matrix metalloproteinase-9 expression in vascular smooth muscle cells. Arterioscler Thromb. Vasc. Biol. 20 (2000) 2527-2532.
  • 116.Huang, C., Jacobson, K. and Schaller, M.D. MAP kinases and cell migration. J. Cell Sci. 117 (2004) 4619-4628.
  • 117.Lian, J., Marcinkiewicz, C., Niewiarowski, S. and Beacham, D.A. Extracellular signal-regulated kinase (ERK) activation is required for GP Ibalpha-dependent endothelial cell migration. Thromb. Haemost. 86 (2001) 1555-1562.
  • 118.Nguyen, L.T., Duncan, G.S., Mirtsos, C., Ng, M., Speiser, D.E., Shahinian, A., Marino, M.W., Mak, T.W., Ohashi, P.S. and Yeh, W.C. TRAF2 deficiency results in hyperactivity of certain TNFR1 signals and impairment of CD40-mediated responses. Immunity 11 (1999) 379-389.
  • 119.Reddy, K.B., Nabha, S.M. and Atanaskova, N. Role of MAP kinase in tumor progression and invasion. Cancer Metastasis Rev. 22 (2003) 395-403.
  • 120.Allen, M.D., Young, L.S. and Dawson, C.W. The Epstein-Barr virusencoded LMP2A and LMP2B proteins promote epithelial cell spreading and motility. J. Virol. 79 (2005) 1789-1802.
  • 121.Cantley, L.C. and Neel, B.G. New insights into tumor suppression: PTEN suppresses tumor formation by restraining the phosphoinositide 3-kinase/AKT pathway. Proc. Natl. Acad. Sci. USA 96 (1999) 4240-4245.
  • 122.Dudek, H., Datta, S.R., Franke, T.F., Birnbaum, M.J., Yao, R., Cooper, G.M., Segal, R.A., Kaplan, D.R. and Greenberg, M.E. Regulation of neuronal survival by the serine-threonine protein kinase Akt. Science 275 (1997) 661-665.
  • 123.Imai, S., Koizumi, S., Sugiura, M., Tokunaga, M., Uemura, Y., Yamamoto, N., Tanaka, S., Sato, E. and Osato, T. Gastric carcinoma: monoclonal epithelial malignant cells expressing Epstein-Barr virus latent infection protein. Proc. Natl. Acad. Sci. USA 91 (1994) 9131-9135.
  • 124.Khwaja, A., Rodriguez-Viciana, P., Wennstrom, S., Warne, P.H. and Downward, J. Matrix adhesion and Ras transformation both activate a phosphoinositide 3-OH kinase and protein kinase B/Akt cellular survival pathway. EMBO J. 16 (1997) 2783-2793.
  • 125.Shaw, L.M., Rabinovitz, I., Wang, H.H., Toker, A. and Mercurio, A.M. Activation of phosphoinositide 3-OH kinase by the alpha6beta4 integrin promotes carcinoma invasion. Cell 91 (1997) 949-960.
  • 126.Cross, D.A., Alessi, D.R., Cohen, P., Andjelkovich, M. and Hemmings, B.A. Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B. Nature 378 (1995) 785-789.
  • 127.Muise-Helmericks, R.C., Grimes, H.L., Bellacosa, A., Malstrom, S.E., Tsichlis, P.N. and Rosen, N. Cyclin D expression is controlled posttranscriptionally via a phosphatidylinositol 3-kinase/Akt-dependent pathway. J. Biol. Chem. 273 (1998) 29864-29872.
  • 128.Brunet, A., Bonni, A., Zigmond, M.J., Lin, M.Z., Juo, P., Hu, L.S., Anderson, M.J., Arden, K.C., Blenis, J. and Greenberg, M.E. Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell 96 (1999) 857-868.
  • 129.Cardone, M.H., Roy, N., Stennicke, H.R., Salvesen, G.S., Franke, T.F., Stanbridge, E., Frisch, S. and Reed, J.C. Regulation of cell death protease caspase-9 by phosphorylation. Science 282 (1998) 1318-1321.
  • 130.Swart, R., Ruf, I.K., Sample, J. and Longnecker, R. Latent membrane protein 2A-mediated effects on the phosphatidylinositol 3-Kinase/Akt pathway. J. Virol. 74 (2000) 10838-10845.
  • 131.Fukuda, M., Ikuta, K., Yanagihara, K., Tajima, M., Kuratsune, H., Kurata, T. and Sairenji, T. Effect of transforming growth factor-beta1 on the cell growth and Epstein-Barr virus reactivation in EBV-infected epithelial cell lines. Virology 288 (2001) 109-118.
  • 132.Fukuda, M. and Longnecker, R. Latent membrane protein 2A inhibits transforming growth factor-beta 1-induced apoptosis through the phosphatidylinositol 3-kinase/Akt pathway. J. Virol. 78 (2004) 1697-1705.
  • 133.Lu, J., Lin, W.H., Chen, S.Y., Longnecker, R., Tsai, S.C., Chen, C.L. and Tsai, C.H. Syk tyrosine kinase mediates Epstein-Barr virus latent membrane protein 2A-induced cell migration in epithelial cells. J. Biol. Chem. 281 (2006) 8806-8814.
  • 134.Inman, G.J. and Allday, M.J. Apoptosis induced by TGF-beta 1 in Burkitt's lymphoma cells is caspase 8 dependent but is death receptor independent. J. Immunol. 165 (2000) 2500-2510.
  • 135.Ohta, S., Yanagihara, K. and Nagata, K. Mechanism of apoptotic cell death of human gastric carcinoma cells mediated by transforming growth factor beta. Biochem. J. 324 ( Pt 3) (1997) 777-782.
  • 136.Saltzman, A., Munro, R., Searfoss, G., Franks, C., Jaye, M. and Ivashchenko, Y. Transforming growth factor-beta-mediated apoptosis in the Ramos B-lymphoma cell line is accompanied by caspase activation and Bcl-XL downregulation. Exp. Cell Res. 242 (1998) 244-254.
  • 137.Schrantz, N., Blanchard, D.A., Auffredou, M.T., Sharma, S., Leca, G. and Vazquez, A. Role of caspases and possible involvement of retinoblastoma protein during TGFbeta-mediated apoptosis of human B lymphocytes. Oncogene 18 (1999) 3511-3519.
  • 138.Chen, R.H., Su, Y.H., Chuang, R.L. and Chang, T.Y. Suppression of transforming growth factor-beta-induced apoptosis through a phosphatidylinositol 3-kinase/Akt-dependent pathway. Oncogene 17 (1998) 1959-1968.
  • 139.Ihle, J.N. and Kerr, I.M. Jaks and Stats in signaling by the cytokine receptor superfamily. Trends Genet. 11 (1995) 69-74.
  • 140.Gilmore, T.D. Introduction to NF-kappaB: players, pathways, perspectives. Oncogene 25 (2006) 6680-6684.
  • 141.Karin, M., Cao, Y., Greten, F.R. and Li, Z.W. NF-kappaB in cancer: from innocent bystander to major culprit. Nat. Rev. Cancer 2 (2002) 301-310.
  • 142.Yu, H. and Jove, R. The STATs of cancer--new molecular targets come of age. Nat. Rev. Cancer 4 (2004) 97-105.
  • 143.Rayet, B. and Gelinas, C. Aberrant rel/nfkb genes and activity in human cancer. Oncogene 18 (1999) 6938-6947.
  • 144.Stewart, S., Dawson, C.W., Takada, K., Curnow, J., Moody, C.A., Sixbey, J.W. and Young, L.S. Epstein-Barr virus-encoded LMP2A regulates viral and cellular gene expression by modulation of the NF-kappaB transcription factor pathway. Proc. Natl. Acad. Sci. USA 101 (2004) 15730-15735.
  • 145.Eliopoulos, A.G., Stack, M., Dawson, C.W., Kaye, K.M., Hodgkin, L., Sihota, S., Rowe, M. and Young, L.S. Epstein-Barr virus-encoded LMP1 and CD40 mediate IL-6 production in epithelial cells via an NF-kappaB pathway involving TNF receptor-associated factors. Oncogene 14 (1997) 2899-2916.
  • 146.Imai, S., Nishikawa, J. and Takada, K. Cell-to-cell contact as an efficient mode of Epstein-Barr virus infection of diverse human epithelial cells. J. Virol. 72 (1998) 4371-4378.
  • 147.Niedobitek, G., Young, L.S., Sam, C.K., Brooks, L., Prasad, U. and Rickinson, A.B. Expression of Epstein-Barr virus genes and of lymphocyte activation molecules in undifferentiated nasopharyngeal carcinomas. Am. J. Pathol. 140 (1992) 879-887.
  • 148.Nishikawa, J., Imai, S., Oda, T., Kojima, T., Okita, K. and Takada, K. Epstein-Barr virus promotes epithelial cell growth in the absence of EBNA2 and LMP1 expression. J. Virol. 73 (1999) 1286-1292.
  • 149.Sugiura, M., Imai, S., Tokunaga, M., Koizumi, S., Uchizawa, M., Okamoto, K. and Osato, T. Transcriptional analysis of Epstein-Barr virus gene expression in EBV-positive gastric carcinoma: unique viral latency in the tumour cells. Br. J. Cancer 74 (1996) 625-631.
  • 150.Seitz, C.S., Lin, Q., Deng, H. and Khavari, P.A. Alterations in NF-kappaB function in transgenic epithelial tissue demonstrate a growth inhibitory role for NF-kappaB. Proc. Natl. Acad. Sci. USA 95 (1998) 2307-2312.
  • 151. Scheid, M.P. and Woodgett, J.R. PKB/AKT: functional insights from genetic models. Nat. Rev. Mol. Cell Biol. 2 (2001) 760-768.
  • 152.Lu, X.L., Liang, Z.H., Zhang, C.E., Lu, S.J., Weng, X.F. and Wu, X.W. Induction of the Epstein-Barr virus latent membrane protein 2 antigenspecific cytotoxic T lymphocytes using human leukocyte antigen tetramerbased artificial antigen-presenting cells. Acta. Biochim. Biophys. Sin. (Shanghai) 38 (2006) 157-163.
  • 153.Pan, Y., Zhang, J., Zhou, L., Zuo, J. and Zeng, Y. In vitro anti-tumor immune response induced by dendritic cells transfected with EBV-LMP2 recombinant adenovirus. Biochem. Biophys. Res. Commun. 347 (2006) 551-557.
  • 154.Ranieri, E., Herr, W., Gambotto, A., Olson, W., Rowe, D., Robbins, P.D., Kierstead, L.S., Watkins, S.C., Gesualdo, L. and Storkus, W.J. Dendritic cells transduced with an adenovirus vector encoding Epstein-Barr virus latent membrane protein 2B: a new modality for vaccination. J. Virol. 73 (1999) 10416-10425.
  • 155.Swanson-Mungerson, M., Ikeda, M., Lev, L., Longnecker, R. and Portis, T. Identification of latent membrane protein 2A (LMP2A) specific targets for treatment and eradication of Epstein-Barr virus (EBV)-associated diseases. J. Antimicrob. Chemother. 52 (2003) 152-154.

Typ dokumentu

Bibliografia

Identyfikatory

Identyfikator YADDA

bwmeta1.element.agro-article-ccd5e16f-35e7-4239-8b2a-5c99a0730207
JavaScript jest wyłączony w Twojej przeglądarce internetowej. Włącz go, a następnie odśwież stronę, aby móc w pełni z niej korzystać.