TRANSCRIPTIONAL ANTAGONISM BETWEEN P53 AND SV40 T-ANTIGEN

In this communication we show that overexpression of the human TATA-binding protein (TBP) activates a synthetic promoter with p53-binding sites in the presence of wild-type p53. No activation is observed in the absence of wild-type p53 in Saos-2 cells. Perhaps, TBP is limiting in these cells for the p53-mediated activation, and p53 activates promoters with p53-binding sites via its interaction with TBP. Using in vivo transient transfection-transcription assays, we also show that wild-type human p53 inhibits simian virus 40 (SV40) late promoter transactivation by SV40 T antigen, but excess T antigen partially releases this inhibition. Recently both T antigen and p53 have been shown to interact with TBP. The inhibition of T antigen-mediated SV40 late promoter activation by p53 or the inhibition of p53-mediated activation of a promoter with p53-binding sites by T antigen is not released by an overexpression of TBP. Thus, the transcriptional antagonism between p53 and T antigen are not at the level of competition for TBP. Possibly, the two proteins poison each other so that they cannot interact with the transcription machinery.