COOPERATIVE DNA-BINDING OF P53 WITH TFIID (TBP) - A POSSIBLE MECHANISM FOR TRANSCRIPTIONAL ACTIVATION

The p53 tumor-suppressor gene product, a sequence-specific DNA-binding protein, has been shown to act both as a transcriptional activator an d repressor in vivo and in vitro. Consistent with its roles in regulat ing transcription are recent observations that p53 binds directly to t he TATA box-binding protein (TBP) subunit of the basal transcription f actor TFIID. Here, we show that p53 cooperates with either recombinant TBP or partially purified TFIID in binding to a DNA fragment containi ng both a specific p53-binding site (RGC) and a TATA box (RGC-TATA). S urprisingly, both TBP and TFIID also stimulate p53 binding to DNA cont aining a specific p53-binding site but lacking a TATA box. These data are supported by the observation that p53 and Drosophila TBP combinato rily activate transcription in vivo. Our results suggest that p53 acti vates transcription through the formation of a more stable p53-TFIID-p romoter complex. We also examined whether p53 might affect the ability of TBP or TFIID to interact with DNA containing a TATA box but lackin g a p53-binding site. Although p53 strongly inhibited the interaction of TBP with such DNA, it had virtually no effect on TFIID binding. Thu s, transcriptional repression by p53 may require additional functions other than inhibiting TBP binding.