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 activator that can be targeted to its DNA responsive elements by direct interaction with the cellular protein RBP-J kappa. RBP-J kappa is a ubiquitous factor, highly conserved between man, mouse and Drosophila, whose function in mammalian cells is largely unknown. Here we provide evidence that RBP-J kappa is a transcriptional repressor and, more importantly, that RBP-J kappa repression is mediated by a co-repressor. The function of the co-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 protein incapable of making physical contact with RBP-J kappa. Our results suggest that EBNA2 activates transcription by both interfering with the function of a co-repressor recruited by RBP-J kappa and providing an activation domain.
Waltzer
L
L
Unit de Virologie Humaine, ENS-INSERM U412, Ecole Normale Supérieure de Lyon, France.
Bourillot
P Y
PY
Sergeant
A
A
Manet
E
E
D000818:Animals; D000956:Antigens, Viral / Q000378:metabolism*; D001483:Base Sequence; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004330:Drosophila; D019309:Epstein-Barr Virus Nuclear Antigens; D004854:Herpesvirus 4, Human / Q000378:metabolism; D006801:Humans; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D012097:Repressor Proteins / Q000378:metabolism; D015533:Transcriptional Activation
D000956:Antigens, Viral; D004268:DNA-Binding Proteins; D019309:Epstein-Barr Virus Nuclear Antigens; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; D009687:Nuclear Proteins; C497570:RBPJ protein, human; C497571:Rbpj protein, mouse; D012097:Repressor Proteins