title: An adenovirus E1A transcriptional repressor domain functions as an activator when tethered to a promoter.
abstract: The adenovirus E1A protein contains three well conserved regions, designated conserved region (CR) 1, 2 and 3, which are important for the multiple activities ascribed to E1A. The CR3 domain constitutes a prototypic transcription activator, consisting of a promoter targeting region and a transactivating region. Here we demonstrate the existence of a second transactivating region located within amino acids 28 to 90 (essentially the CR1 domain) of the E1A protein. A fusion protein, containing the Gal4 DNA binding domain linked to CR1, was as efficient as the classical CR3 transactivator in activating transcription from a reporter plasmid containing Gal4 binding sites. However, competition experiments suggest that Gal/CR1 and Gal/CR3 work through different cellular targets. The E1A-243R protein has previously been extensively characterized as a repressor of transcription. Here we show that a Gal4 fusion protein expressing the CR1 domain is indeed sufficient for repression of SV40 enhancer activity. Collectively, our results suggest that CR1 functions as an activator if tethered to a promoter and as a repressor in the absence of promoter association.
authors.affiliation: Department of Cell and Molecular Biology, Medical Nobel Institute, Karolinska Institutet, Stockholm, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Bondesson
authors.forename: M
authors.initials: M
authors.lastname: Mannervik
authors.forename: G
authors.initials: G
authors.lastname: Akusjärvi
authors.forename: C
authors.initials: C
authors.lastname: Svensson
mesh_terms: D017500:Adenovirus E1A Proteins / Q000737:chemistry* / Q000235:genetics; D001665:Binding Sites; D001667:Binding, Competitive; D004268:DNA-Binding Proteins; D004357:Drug Synergism; D004742:Enhancer Elements, Genetic; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D007163:Immunosorbent Techniques; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D013539:Simian virus 40 / Q000235:genetics; D013329:Structure-Activity Relationship; D014157:Transcription Factors; D014158:Transcription, Genetic; D015533:Transcriptional Activation
chemical_list: D017500:Adenovirus E1A Proteins; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C052130:GAL4 protein, S cerevisiae; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors