2 DOMAINS OF P53 INTERACT WITH THE TATA-BINDING PROTEIN, AND THE ADENOVIRUS-13S E1A-PROTEIN DISRUPTS THE ASSOCIATION, RELIEVING P53-MEDIATED TRANSCRIPTIONAL REPRESSION

The tumor suppressor gene product p53 can activate and repress transcr iption. Both transcriptional activation and repression are thought to involve the direct interaction of p53 with the basal transcriptional m achinery. Previous work has demonstrated an in vitro interaction betwe en p53 and the TATA-binding protein that requires amino acids 20 to 57 of p53 and amino acids 220 to 271 of the TATA-binding protein. The pr esent results show that a 75-amino-acid segment from the carboxy termi nus of p53 also can bind to the TATA-binding protein in vitro, and thi s interaction requires amino acids 217 to 268 of the TATA-binding prot ein, essentially the same domain that is required for interaction with the amino-terminal domain of p53. A carboxy-terminal segment of p53 c an mediate repression when bound to DNA as a GAL4-p53 fusion protein. The amino- and carboxy-terminal p53 interactions occur within the doma in on the TATA-binding protein to which the adenovirus 13S ELA oncopro tein has previously been shown to bind. The 13S E1A oncoprotein can di ssociate the complex formed between the carboxy-terminal domain of p53 and the TATA-binding protein and relieve p53-mediated transcriptional repression. These results demonstrate that two independent domains of p53 can potentially interact with the TATA-binding protein, and they define a mechanism-relief of repression-by which the 13S E1A oncoprote in can activate transcription through the TATA motif.