Epstein-Barr virus EBNA3A and EBNA3C proteins both repress RBP-J kappa-EBNA2-activated transcription by inhibiting the binding of RBP-J kappa to DNA.
Following infection by Epstein-Barr virus (EBV), the production of viral nuclear proteins EBNA1, EBNA2, EBNA3A, and EBNA3C and the viral membrane protein LMP1 is essential for the permanent proliferation of primary B lymphocytes to occur. Among these, the transcription factor EBNA2 is central to the immortalizing process, since it activates not only the transcription of all the EBNA proteins and LMP1, TP1, and TP2 but also certain cellular genes. EBNA2 is targeted to its DNA-responsive elements through direct interaction with the DNA-binding cellular repressor RBP-J kappa. In a transient-expression assay, the EBNA2-activated transcription was found to be downregulated by EBNA3A, EBNA3B, and EBNA3C. However, since it has been reported that EBNA3C, but not EBNA3A, directly contacts RBP-J kappa in vitro, these proteins appear to repress through different mechanisms. Here, we report for the first time that EBNA3A and EBNA3C both stably interact with RBP-J kappa and most probably repress EBNA2-activated transcription by destabilizing the binding of RBP-J kappa to DNA.
Waltzer
L
L
Unité de Virologie Humaine, U412 INSERM, Ecole Normale Supérieure de Lyon, France.
Perricaudet
M
M
Sergeant
A
A
Manet
E
E
D000956:Antigens, Viral / Q000378:metabolism*; D001402:B-Lymphocytes; D001483:Base Sequence; D015500:Chloramphenicol O-Acetyltransferase / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D019309:Epstein-Barr Virus Nuclear Antigens; D006367:HeLa Cells; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009687:Nuclear Proteins; D009838:Oligodeoxyribonucleotides; D016133:Polymerase Chain Reaction; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D015183:Restriction Mapping; D015534:Trans-Activators / Q000378:metabolism; D015533:Transcriptional Activation; D014162:Transfection
D000956:Antigens, Viral; D017931:DNA Primers; D004268:DNA-Binding Proteins; D019309:Epstein-Barr Virus Nuclear Antigens; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; D009687:Nuclear Proteins; D009838:Oligodeoxyribonucleotides; C497570:RBPJ protein, human; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D004247:DNA; D015500:Chloramphenicol O-Acetyltransferase