Implementación de la solución

We would like to thank Dr. Fred Wang for the template for our Rh-L2A and Rh-L2A∆C constructs. Additionally, we would like to thank Dr. Kathy Ho Yen Shair for critical review of this manuscript. This work was supported by grant CA103634 from the National

REFERENCES

1. Alfandari, J., S. Shnitman Magal, A. Jackman, R. Schlegel, P. Gonen, and L. Sherman. 1999. HPV16 E6 oncoprotein inhibits apoptosis induced during serum- calcium differentiation of foreskin human keratinocytes. Virology 257:383-96. 2. Brazil, D. P., and B. A. Hemmings. 2001. Ten years of protein kinase B signalling:

a hard Akt to follow. Trends Biochem Sci 26:657-64.

3. Cross, D. A., D. R. Alessi, P. Cohen, M. Andjelkovich, and B. A. Hemmings. 1995. Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B. Nature 378:785-9.

4. Ding, V. W., R. H. Chen, and F. McCormick. 2000. Differential regulation of glycogen synthase kinase 3beta by insulin and Wnt signaling. J Biol Chem 275:32475-81.

5. Farwell, D. G., K. A. Shera, J. I. Koop, G. A. Bonnet, C. P. Matthews, G. W. Reuther, M. D. Coltrera, J. K. McDougall, and A. J. Klingelhutz. 2000. Genetic and epigenetic changes in human epithelial cells immortalized by telomerase. Am J Pathol 156:1537-47.

6. Feichtinger, H., E. Kaaya, P. Putkonen, S. L. Li, M. Ekman, R. Gendelman, G. Biberfeld, and P. Biberfeld. 1992. Malignant lymphoma associated with human AIDS and with SIV-induced immunodeficiency in macaques. AIDS Res Hum Retroviruses 8:339-48.

7. Feichtinger, H., P. Putkonen, C. Parravicini, S. L. Li, E. E. Kaaya, D. Bottiger, G. Biberfeld, and P. Biberfeld. 1990. Malignant lymphomas in cynomolgus monkeys infected with simian immunodeficiency virus. Am J Pathol 137:1311-5. 8. Fruehling, S., and R. Longnecker. 1997. The immunoreceptor tyrosine-based

activation motif of Epstein-Barr virus LMP2A is essential for blocking BCR- mediated signal transduction. Virology 235:241-51.

9. Habis, A., G. B. Baskin, M. Murphey-Corb, and L. S. Levy. 1999. Simian AIDS- associated lymphoma in rhesus and cynomolgus monkeys recapitulates the primary pathobiological features of AIDS-associated non-Hodgkin's lymphoma. AIDS Res Hum Retroviruses 15:1389-98.

10. Ikeda, A., R. G. Caldwell, R. Longnecker, and M. Ikeda. 2003. Itchy, a Nedd4 ubiquitin ligase, downregulates latent membrane protein 2A activity in B-cell signaling. J Virol 77:5529-34.

11. Kutok, J. L., S. Klumpp, M. Simon, J. J. MacKey, V. Nguyen, J. M. Middeldorp, J. C. Aster, and F. Wang. 2004. Molecular evidence for rhesus lymphocryptovirus infection of epithelial cells in immunosuppressed rhesus macaques. J Virol 78:3455- 61.

12. Longnecker, R., C. L. Miller, X. Q. Miao, B. Tomkinson, and E. Kieff. 1993. 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 67:2006-13.

13. Longnecker, R., C. L. Miller, B. Tomkinson, X. Q. Miao, and E. Kieff. 1993. Deletion of DNA encoding the first five transmembrane domains of Epstein-Barr virus latent membrane proteins 2A and 2B. J Virol 67:5068-74.

14. Moghaddam, A., J. Koch, B. Annis, and F. Wang. 1998. Infection of human B lymphocytes with lymphocryptoviruses related to Epstein-Barr virus. J Virol 72:3205-12.

15. Moghaddam, A., M. Rosenzweig, D. Lee-Parritz, B. Annis, R. P. Johnson, and F. Wang. 1997. An animal model for acute and persistent Epstein-Barr virus infection. Science 276:2030-3.

16. Morrison, J. A., M. L. Gulley, R. Pathmanathan, and N. Raab-Traub. 2004. Differential signaling pathways are activated in the Epstein-Barr virus-associated malignancies nasopharyngeal carcinoma and Hodgkin lymphoma. Cancer Res 64:5251-60.

17. Morrison, J. A., A. J. Klingelhutz, and N. Raab-Traub. 2003. Epstein-Barr virus latent membrane protein 2A activates beta-catenin signaling in epithelial cells. J Virol 77:12276-84.

18. Morrison, J. A., and N. Raab-Traub. 2005. Roles of the ITAM and PY motifs of Epstein-Barr virus latent membrane protein 2A in the inhibition of epithelial cell differentiation and activation of {beta}-catenin signaling. J Virol 79:2375-82. 19. Novak, A., and S. Dedhar. 1999. Signaling through beta-catenin and Lef/Tcf. Cell

Mol Life Sci 56:523-37.

20. Rickinson, A., and E. Kieff. 1996. Epstein-Barr virus, p. 2397-2446. In B. F. D. Knipe, and P. Howley (ed.), Fields virology. Raven Press, Philadelphia.

21. Rivailler, P., Y. G. Cho, and F. Wang. 2002. Complete genomic sequence of an Epstein-Barr virus-related herpesvirus naturally infecting a new world primate: a defining point in the evolution of oncogenic lymphocryptoviruses. J Virol 76:12055- 68.

22. Scholle, F., K. M. Bendt, and N. Raab-Traub. 2000. Epstein-Barr virus LMP2A transforms epithelial cells, inhibits cell differentiation, and activates Akt. J Virol 74:10681-9.

23. Scholle, F., R. Longnecker, and N. Raab-Traub. 2001. Analysis of the

phosphorylation status of Epstein-Barr virus LMP2A in epithelial cells. Virology 291:208-14.

24. Swart, R., I. K. Ruf, J. Sample, and R. Longnecker. 2000. Latent membrane protein 2A-mediated effects on the phosphatidylinositol 3-Kinase/Akt pathway. J Virol 74:10838-45.

25. Yang, L., H. C. Dan, M. Sun, Q. Liu, X. M. Sun, R. I. Feldman, A. D. Hamilton, M. Polokoff, S. V. Nicosia, M. Herlyn, S. M. Sebti, and J. Q. Cheng. 2004.

Akt/protein kinase B signaling inhibitor-2, a selective small molecule inhibitor of Akt signaling with antitumor activity in cancer cells overexpressing Akt. Cancer Res 64:4394-9.