title: Concerted expression of BK virus large T- and small t-antigens strongly enhances oestrogen receptor-mediated transcription.
abstract: Previous studies have shown that the human polyomavirus BK (BKV) genome contains an oestrogen response element (ERE). This isolated element binds its cognate receptor in vitro and can mediate 17beta-oestradiol-induced gene expression when linked to a heterologous promoter. The roles of the ERE- and the AP-1-binding sites in oestrogen receptor-directed transcription from the complete BKV promoter/enhancer (Dunlop strain) have been examined and the effects of the general co-activator CBP and large T- and small t-antigens on oestrogen receptor-mediated transcription have been investigated. A constitutive activated oestrogen receptor stimulated BKV promoter activity in HeLa cells. Mutations in either the ERE- or the AP-1-binding sites did not impair oestrogen receptor-induced activation of the BKV Dunlop promoter, while mutations in both binding motifs almost completely abolished oestrogen receptor-induced transcription. Simultaneous expression of large T- and small t-antigens strongly activated oestrogen receptor-mediated transcription. When expressed separately, only large T-antigen moderately stimulated oestrogen receptor-mediated transcription. The stimulatory effect of large T-antigen on the activity of the oestrogen receptor is probably indirect because no physical interaction between the two proteins was detected in a two-hybrid assay. Large T-antigen abrogated the synergistic effect on transcription between this nuclear receptor and the general co-activator CBP. The findings that the BKV early proteins amplify oestrogen receptor-mediated transcription may have important biological implications in individuals with raised oestrogen concentrations.
authors: U
authors: U
authors: Moens
authors: M
authors: M
authors: Van Ghelue
authors: B
authors: B
authors: Johansen
authors: O M
authors: OM
authors: Seternes
mesh_terms: D000952:Antigens, Polyomavirus Transforming / Q000235:genetics / Q000378:metabolism*; D001739:BK Virus / Q000235:genetics* / Q000276:immunology; D001483:Base Sequence; D050882:CREB-Binding Protein; D004305:Dose-Response Relationship, Drug; D004742:Enhancer Elements, Genetic / Q000235:genetics; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D005814:Genes, Viral / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011485:Protein Binding; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*; D020218:Response Elements / Q000235:genetics; D015534:Trans-Activators / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000502:physiology; D015533:Transcriptional Activation; D014162:Transfection
chemical_list: D000952:Antigens, Polyomavirus Transforming; D009687:Nuclear Proteins; D011960:Receptors, Estrogen; D015534:Trans-Activators; D018808:Transcription Factor AP-1; D050882:CREB-Binding Protein; C494363:CREBBP protein, human