Identification of a novel class of genomic DNA-binding sites suggests a mechanism for selectivity in target gene activation by the tumor suppressor protein p53

Abstract

There are two response elements for p53 in the promoter of the gene for the cyclin-dependent kinase inhibitor p21. The binding of p53 to the 5′ site was enhanced by incubation with monoclonal antibody 421, whereas the binding of p53 to the 3′ site was inhibited. Mutational analysis showed that a single-base change caused one element to behave like the other. A response element in the humancdc25C promoter is bound by p53 with properties similar to the 3′ site. These results identify two classes of p53-binding sites and suggest a mechanism for target gene selectivity by p53.

Keywords

• Tumor suppressor
• DNA binding
• sequence specificity
• p53 protein
• transcriptional activation
• binding sites