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Faumont, N.* ; Durand-Panteix, S.* ; Schlee, M. ; Grömminger, S. ; Schuhmacher, M.* ; Hölzel, M. ; Laux, G. ; Mailhammer, R. ; Rosenwald, A.* ; Staudt, L.M.* ; Bornkamm, G.W. ; Feuillard, J.*

C-Myc and Rel/NF-κB are the two master transcriptional systems activated in the latency III program of Epstein-Barr virus-immortalized B cells.

J. Virol. 83, 5014-5027 (2009)
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The Epstein-Barr virus (EBV) latency III program imposed by EBNA2 and LMP1 is directly responsible for immortalization of B cells in vitro and is thought to mediate most immunodeficiency-related posttransplant lymphoproliferative diseases in vivo. To answer the question whether and how this proliferation program is related to c-Myc, we have established the transcriptome of both c-Myc and EBV latency III proliferation programs using a Lymphochip specialized microarray. In addition to EBV-positive latency I Burkitt lymphoma lines and lymphoblastoid cell lines (LCLs), we used an LCL expressing an estrogen-regulatable EBNA2 fusion protein (EREB2-5) and derivative B-cell lines expressing a constitutively active or tetracycline-regulatable c-myc gene. A total of 897 genes were found to be fourfold or more up- or downregulated in either one or both proliferation programs compared to the expression profile of resting EREB2-5 cells. A total of 661 (74%) of these were regulated similarly in both programs. Numerous repressed genes were known targets of STAT1, and most induced genes were known to be upregulated by c-Myc and to be involved in cell proliferation. In keeping with the gene expression patterns, inactivation of c-Myc by a chemical inhibitor or by conditional expression of dominant-negative c-Myc and Max mutants led to proliferation arrest of LCLs. Most genes differently regulated in both proliferation programs corresponded to genes induced by NF-kappa B in LCLs, and many of them coded for immunoregulatory and/or antiapoptotic molecules. Thus, c-Myc and NF-kappa B are the two main transcription factors responsible for the phenotype, growth pattern, and biological properties of cells driven into proliferation by EBV.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords burkitts-lymphoma cells; non-hodgkins-lymphomas; nuclear antigen-2; lymphoproliferative disorders; lymphoblastoid-cells; down-regulation; cycle arrest; apoptosis; expression; ebna2
ISSN (print) / ISBN 0022-538X
e-ISSN 1098-5514
Journal Journal of Virology
Quellenangaben Volume: 83, Issue: 10, Pages: 5014-5027 Article Number: , Supplement: ,
Publisher American Society for Microbiology (ASM)
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Research Unit Gene Vector (AGV)
Institute of Clinical Molecular Biology and Tumor Genetics (K.MOLBI)