IDENTIFICATION OF A NOVEL CLASS OF GENOMIC DNA-BINDING SITES SUGGESTSA MECHANISM FOR SELECTIVITY IN TARGET GENE ACTIVATION BY THE TUMOR-SUPPRESSOR PROTEIN P53

There are two response elements for p53 in the promoter of the gene fo r the cyclin-dependent kinase inhibitor p21. The binding of p53 to the 5' site was enhanced by incubation with monoclonal antibody 421, wher eas the binding of p53 to the 3' site was inhibited. Mutational analys is showed that a single-base change caused one element to behave like the other. ih response element in the human cdc25C promoter is bound b y p53 with properties similar to the 3' site. These results identify t wo classes of p53-binding sites and suggest a mechanism for target gen e selectivity by p53.