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 vir al nuclear proteins EBNA1, EBNA2, EBNA3A, and EBNA3C and the viral mem brane protein LMP1 is essential for the permanent proliferation of pri mary B lymphocytes to occur. Among these, the transcription factor EBN A2 is central to the immortalizing process, since it activates not onl y the transcription of all the EBNA proteins and LMP1, TP1, and TP2 bu t also certain cellular genes. EBNA2 is targeted to its DNA-responsive elements through direct interaction with the DNA-binding cellular rep ressor RBP-J kappa. In a transient-expression assay, the EBNA2-activat ed transcription was found to be downregulated by EBNA3A, EBNA3B, and EBNA3C. However, since it has been reported that EBNA3C, but not EBNA3 A, directly contacts RBP-J kappa in vitro, these proteins appear to re press 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 b inding of RBP-J kappa to DNA.