Analysis ofa Protein-Binding Domainofp53

protein andsubsequently was foundtofunction incell proliferation control. Tumor-derived mutations inp53occur predominantly infourevolutionarily conserved regions spanning approximately 50% ofthepolypeptide. Previously, three ofthese regions were identified asessential forT-antigen binding. We haveexaminedthe interaction between p53andT antigen byusing Escherichia coli-expressed humanp53.Bya combination of deletion analysis andantibody inhibition studies, a region ofp53thatisbothnecessaryandsufficient for binding toTantigen hasbeenlocalized. Thisfunction iscontained within residues 94to293,whichinclude the fourconserved regions affected bymutation intumors. Residues 94to293ofp53were expressed inboth wild-type andmutantforms. T-antigen binding was unaffected bytumor-derived mutations whichhavebeen associated withthewild-type conformation ofp53butwas greatly reduced bymutations whichwere previously showntoalter p53conformation. Ourresults showthat, likeT-antigen binding totheRb tumorsuppressor protein, T antigen appearstointeract withthedomainofp53thatiscommonlymutated inhumantumors.