ANALYSIS OF A PROTEIN-BINDING DOMAIN OF P53

The tumor suppressor protein p53 was first isolated as a simian virus 40 large T antigen-associated protein and subsequently was found to fu nction in cell proliferation control. Tumor-derived mutations in p53 o ccur predominantly in four evolutionarily conserved regions spanning a pproximately 50% of the polypeptide. Previously, three of these region s were identified as essential for T-antigen binding. We have examined the interaction between p53 and T antigen by using Escherichia coli-e xpressed human p53. By a combination of deletion analysis and antibody inhibition studies, a region of p53 that is both necessary and suffic ient for binding to T antigen has been localized. This function is con tained within residues 94 to 293, which include the four conserved reg ions affected by mutation in tumors. Residues 94 to 293 of p53 were ex pressed in both wild-type and mutant forms. T-antigen binding was unaf fected by tumor-derived mutations which have been associated with the wild-type conformation of p53 but was greatly reduced by mutations whi ch were previously shown to alter p53 conformation. Our results show t hat, like T-antigen binding to the Rb tumor suppressor protein, T anti gen appears to interact with the domain of p53 that is commonly mutate d in human tumors.