title: Dominant-negative inhibitors of EBNA-1 of Epstein-Barr virus.
abstract: Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA-1) is required in trans to support replication of the EBV genome once per cell cycle via the latent origin of replication, oriP. EBNA-1 can also activate transcription on binding to the family of repeats of oriP to enhance some heterologous as well as native EBV promoters. We have made and screened derivatives of EBNA-1 for the ability to act as inhibitors of wild-type EBNA-1. These derivatives lack the linking or the retention functions of EBNA-1 and were analyzed for the residual ability to activate transcription and replication. We have identified derivatives of EBNA-1 that can inhibit up to 98% of wild-type EBNA-1's activities. We have also identified one derivative of EBNA-1 with only two of EBNA-1's three linking domains which can support transcription and replication inefficiently.
authors.affiliation: McArdle Laboratory for Cancer Research, University of Wisconsin Medical School, Madison 53706, USA.
authors.forename: A L
authors.initials: AL
authors.lastname: Kirchmaier
authors.forename: B
authors.initials: B
authors.lastname: Sugden
mesh_terms: D004261:DNA Replication; D019309:Epstein-Barr Virus Nuclear Antigens / Q000235:genetics / Q000378:metabolism*; D004854:Herpesvirus 4, Human / Q000502:physiology*; D016296:Mutagenesis; D010957:Plasmids; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D018741:Replication Origin; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
chemical_list: D019309:Epstein-Barr Virus Nuclear Antigens; D011993:Recombinant Fusion Proteins