BOTH EPSTEIN-BARR VIRAL NUCLEAR ANTIGEN-2 (EBNA2) AND ACTIVATED NOTCH1 TRANSACTIVATE GENES BY INTERACTING WITH THE CELLULAR PROTEIN RBP-JK

The Epstein-Barr viral nuclear antigen 2 (EBNA2) plays a key role duri ng establishment and maintenance of B cell immortalization after Epste in-Barr virus (EBV) infection. EBNA2 acts as a transactivator of cellu lar and viral genes. We studied two EBNA2 regulated viral promoters (T P1 promoter and LMP/TP2 promoter) in detail to learn, more about the m olecular mechanisms of EBNA2-mediated transactivation. In both promote rs me could identify at least one binding site for the cellular repres sor protein RBP-J kappa. EBNA2 is tethered to the EBNA2 responsive pro moter elements by interaction with this cellular protein. Although nec essary, the binding of RBP-JK is not sufficient for EBNA2-mediated tra nsactivation. At least two further cellular proteins, which are differ ent in the studied promoters are important for efficient transactivati on The identification of RBP-J kappa as central mediator of EBNA2 tran sactivation suggested an interference of EBNA2 with the highly conserv ed Notch receptor signal transduction pathway We could show that an ac tivated form of the Notch receptor can transactivate a reporter constr uct containing a hexamer of the two RBP-J kappa binding sites of the T P1 promoter supporting the idea that EBNA2 acts as a functional equiva lent of an activated Notch receptor.