title: Epstein-Barr virus nuclear antigen 3C is a transcriptional regulator.
abstract: Epstein-Barr virus (EBV) nuclear antigen 3C (EBNA-3C) is one of five viral nuclear proteins that are essential for EBV-induced immortalization of primary human B lymphocytes in vitro. Previous studies have implied that EBNA-3C acts as a transcription factor. Using transient transfection assays, we demonstrate that EBNA-3C has two effects on reporter genes that are linked to the latent membrane protein 1 promoter, (i) low-level activation by EBNA-3C alone, as well as potentiation of EBNA-2-mediated transactivation, and (ii) inhibition of the normally strong activation mediated by EBNA-2. These two disparate effects seem to be mediated at different stages following cell feeding. The inhibitory effect of EBNA-3C was localized to a known EBNA-2 response element that had previously been shown to be recognized by the DNA-binding protein RBP-J kappa. In addition, direct interaction between RBP-J kappa and EBNA-3C was observed by coimmunoprecipitation. Activation by EBNA-3C, however, seems to be achieved via sequences that are distinct from RBP-J kappa sites, since activation remained even after these sites had been mutated. Consistent with its ability to activate transcription, a region of EBNA-3C which has homology to the glutamine-rich activation domain of Sp1 can function as a transcription activation domain when it is fused to the heterologous DNA-binding domain of Gal4 and can partially restore the activity of a mutant EBNA-2 protein with a deletion in the transactivation domain. Collectively, these data strongly support the role of EBNA-3C as a transcriptional regulator.
authors.affiliation: Department of Virology and Molecular Biology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
authors.forename: D
authors.initials: D
authors.lastname: Marshall
authors.forename: C
authors.initials: C
authors.lastname: Sample
mesh_terms: D000956:Antigens, Viral / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D019309:Epstein-Barr Virus Nuclear Antigens; D006801:Humans; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D015534:Trans-Activators / Q000378:metabolism*; D015533:Transcriptional Activation; D014763:Viral Matrix Proteins / Q000235:genetics
chemical_list: D000956:Antigens, Viral; D004268:DNA-Binding Proteins; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D019309:Epstein-Barr Virus Nuclear Antigens; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; D009687:Nuclear Proteins; C497570:RBPJ protein, human; D015534:Trans-Activators; D014763:Viral Matrix Proteins