Concerted expression of BK virus large T- and small t-antigens strongly enhances oestrogen receptor-mediated transcription

Previous studies have shown that the human polyomavirus Ph (BKV) genome con tains an oestrogen response element (ERE). This isolated element binds its cognate receptor in vitro and can mediate 17 beta-oestradiol-induced gene e xpression when linked to a heterologous promoter. The roles of the ERE- and the AP-1-binding sites in oestrogen receptor-directed transcription from t he complete BKV promoter/enhancer (Dunlop strain) have been examined and th e effects of the general co-activator CBP and large T- and small t-antigens on oestrogen receptor-mediated transcription have been investigated. A con stitutive activated oestrogen receptor stimulated BKV promoter activity in HeLa cells. Mutations in either the ERE- or the AP-l-binding sites did not impair oestrogen receptor-induced activation of the BKV Dunlop promoter, wh ile mutations in both binding motifs almost completely abolished oestrogen receptor-induced transcription. Simultaneous expression of large T- and sma ll t-antigens strongly activated oestrogen receptor-mediated transcription. When expressed separately, only large T-antigen moderately stimulated oest rogen receptor-mediated transcription. The stimulatory effect of large T-an tigen on the activity of the oestrogen receptor is probably indirect becaus e no physical interaction between the two proteins was detected in a two-hy brid assay. Large T-antigen abrogated the synergistic effect on transcripti on between this nuclear receptor and the general co-activator CBP. The find ings that the BKV early proteins amplify oestrogen receptor-mediated transc ription may have important biological implications in individuals with rais ed oestrogen concentrations.