title: Physical and functional interactions between the corepressor CtBP and the Epstein-Barr virus nuclear antigen EBNA3C.
abstract: CtBP has been shown to be a highly conserved corepressor of transcription. E1A and all the various transcription factors to which CtBP binds contain a conserved PLDLS CtBP-interacting domain, and EBNA3C includes a PLDLS motif (amino acids [aa] 728 to 732). Here we show that EBNA3C binds to CtBP both in vitro and in vivo and that the interaction requires an intact PLDLS. The C terminus of EBNA3C (aa 580 to 992) has modest trans-repressor activity when it is fused to the DNA-binding domain of Gal4, and deletion or mutation of the PLDLS sequence ablates this and unmasks a transactivation function within the fragment. However, loss of the CtBP interaction motif had little effect on the ability of full-length EBNA3C to repress transcription. A striking correlation between CtBP binding and the capacity of EBNA3C to cooperate with (Ha-)Ras in the immortalization and transformation of primary rat embryo fibroblasts was also revealed.
authors.affiliation: Section of Virology and Cell Biology and Ludwig Institute for Cancer Research, Imperial College of Science, Technology and Medicine, St. Mary's Campus, London W2 1PG, United Kingdom.
authors.forename: R
authors.initials: R
authors.lastname: Touitou
authors.forename: M
authors.initials: M
authors.lastname: Hickabottom
authors.forename: G
authors.initials: G
authors.lastname: Parker
authors.forename: T
authors.initials: T
authors.lastname: Crook
authors.forename: M J
authors.initials: MJ
authors.lastname: Allday
mesh_terms: D000429:Alcohol Oxidoreductases; D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism*; D020031:Epstein-Barr Virus Infections / Q000378:metabolism* / Q000821:virology; D019309:Epstein-Barr Virus Nuclear Antigens / Q000378:metabolism*; D004854:Herpesvirus 4, Human / Q000502:physiology; D006801:Humans; D010750:Phosphoproteins / Q000378:metabolism*; D011485:Protein Binding; D012097:Repressor Proteins / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D004268:DNA-Binding Proteins; D019309:Epstein-Barr Virus Nuclear Antigens; D010750:Phosphoproteins; D012097:Repressor Proteins; D000429:Alcohol Oxidoreductases; C096794:C-terminal binding protein