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Blood, 1 April 2008, Vol. 111, No. 7, pp. 3813-3820. Prepublished online as a Blood First Edition Paper on January 29, 2008; DOI 10.1182/blood-2007-03-080309. This Article Full Text Full Text (PDF) Supplemental Table Erratum (v112,p452) All Versions of this Article: blood-2007-03-080309v1 111/7/3813    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Guasparri, I. Articles by Cesarman, E. Search for Related Content PubMed PubMed Citation Articles by Guasparri, I. Articles by Cesarman, E. Related Collections Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA EBV LMP2A affects LMP1-mediated NF-B signaling and survival of lymphoma cells by regulating TRAF2 expression Ilaria Guasparri1, Darya Bubman1, and Ethel Cesarman1 1 Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY A mechanism used by Epstein-Barr virus (EBV) for in vitro transformation of B cells into lymphoblastoid cell lines (LCLs) is activation of the NF-B pathway, which is largely mediated by the EBV latent membrane protein 1 (LMP1). LMP1 is coexpressed with LMP2A in many EBV-associated lymphoid malignancies. Since inhibition of NF-B leads to apoptosis of EBV-infected LCLs and lymphoma cell lines, we sought to determine whether LMP1 alone, or in combination with other viral proteins, is responsible for initiating NF-B activation in these cells, thereby playing a role in cell survival. We found that suppression of LMP1 by RNA interference results in inhibition of basal NF-B and induction of apoptosis. Unexpectedly, knockdown of LMP2A also resulted in comparable decrease of NF-B activity and apoptosis. We report that LMP2A protein controls the expression of TRAF2 mRNA, which in turn is necessary for signaling by LMP1. Our data contrast with previous studies showing that transfected LMP1 can signal in the absence of LMP2A or TRAF2, and demonstrate that both LMP2A and TRAF2 are required for survival in naturally infected lymphoma cells and LCLs. These results also support LMP1, LMP2A, and TRAF2 as potential therapeutic targets in a subset of EBV-associated lymphoid malignancies. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: N. Faumont, S. Durand-Panteix, M. Schlee, S. Gromminger, M. Schuhmacher, M. Holzel, G. Laux, R. Mailhammer, A. Rosenwald, L. M. Staudt, et al. c-Myc and Rel/NF-{kappa}B Are the Two Master Transcriptional Systems Activated in the Latency III Program of Epstein-Barr Virus-Immortalized B Cells J. Virol., May 15, 2009; 83(10): 5014 - 5027. [Abstract] [Full Text] [PDF] C. Demetriades and G. Mosialos The LMP1 Promoter Can Be Transactivated Directly by NF-{kappa}B J. Virol., May 15, 2009; 83(10): 5269 - 5277. [Abstract] [Full Text] [PDF] A. Carbone, E. Cesarman, M. Spina, A. Gloghini, and T. F. Schulz HIV-associated lymphomas and gamma-herpesviruses Blood, February 5, 2009; 113(6): 1213 - 1224. [Abstract] [Full Text] [PDF]

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