Epstein-Barr virus nuclear antigen 2 is a transcriptional suppressor of the immunoglobulin mu gene: implications for the expression of the translocated c-myc gene in Burkitt's lymphoma cells.
A conditional mutant of Epstein-Barr virus nuclear antigen 2 (EBNA2) regulated by estrogen was employed to study the effect of EBNA2 on the cellular phenotype. Activation of EBNA2 in lymphoblastoid cell lines (LCLs) and in B cell lymphoma lines resulted in down-regulation of cell surface IgM and Ig-mu steady-state RNA expression. In LCLs, activation of EBNA2 is required for maintaining proliferation, whereas in Burkitt's lymphoma (BL) cell lines with t(8;14) translocations, activation of EBNA2 induces growth arrest. In these cells, Northern and nuclear run-on analyses revealed rapid simultaneous repression of Ig-mu and c-myc transcription as early as 30 min after activation of EBNA2. Since c-myc expression is under the control of the Ig heavy chain locus in BL cell lines with a t(8;14) translocation, we propose that Ig-mu and c-myc are down-regulated by EBNA2 through a common mechanism.
Jochner
N
N
Institut für Klinische Molekularbiologie und Tumorgenetik, GSF-Forschungszentrum fur Umwelt und Gesundheit, München, Germany.
Eick
D
D
Zimber-Strobl
U
U
Pawlita
M
M
Bornkamm
G W
GW
Kempkes
B
B
D000956:Antigens, Viral / Q000378:metabolism*; D015152:Blotting, Northern; D002051:Burkitt Lymphoma / Q000235:genetics; D002455:Cell Division; D002467:Cell Nucleus / Q000378:metabolism; D002883:Chromosomes, Human, Pair 14; D002898:Chromosomes, Human, Pair 8; D004268:DNA-Binding Proteins / Q000378:metabolism*; D019309:Epstein-Barr Virus Nuclear Antigens; D015972:Gene Expression Regulation, Neoplastic; D016259:Genes, myc; D006801:Humans; D007075:Immunoglobulin M / Q000096:biosynthesis; D007148:Immunoglobulin mu-Chains / Q000096:biosynthesis; D007700:Kinetics; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis; D011947:Receptors, Antigen, B-Cell / Q000096:biosynthesis; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D013997:Time Factors; D014158:Transcription, Genetic; D014162:Transfection; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured
D000956:Antigens, Viral; D004268:DNA-Binding Proteins; D019309:Epstein-Barr Virus Nuclear Antigens; D007075:Immunoglobulin M; D007148:Immunoglobulin mu-Chains; D016271:Proto-Oncogene Proteins c-myc; D011947:Receptors, Antigen, B-Cell; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins