RBP-J-KAPPA REPRESSION ACTIVITY IS MEDIATED BY A CO-REPRESSOR AND ANTAGONIZED BY THE EPSTEIN-BARR-VIRUS TRANSCRIPTION FACTOR EBNA2

The Epstein-Barr virus (EBV) protein EBNA2 is a transcriptional activa tor that can be targeted to its DNA responsive elements by direct inte raction with the cellular protein RBP-J kappa. RBP-J kappa is a ubiqui tous factor, highly conserved between man, mouse and Drosophila, whose function in mammalian cells is largely unknown, Here we provide evide nce that RBP-J kappa is a transcriptional repressor and, more importan tly, that RBP-J kappa repression is mediated by a co-repressor, The fu nction of the cc-repressor could be counterbalanced by making a fusion protein (RBP-VP16) between RBP-J kappa and the VP16 activation domain , This RBP-VP16-mediated activation could be strongly increased by an EBNA2 protein deprived of its activation domain, but not by an EBNA2 p rotein incapable of making physical contact with RBP-J kappa. Our resu lts suggest that EBNA2 activates transcription by both interfering wit h the function of a co-repressor recruited by RBP-J kappa and providin g an activation domain.