Wild-Type Human p53 Transactivates the Human Proliferating Cell Nuclear Antigen Promoter

Abstract

The wild-type p53 protein is a transcriptional activator implicated in the control of cellular growth-related gene expression. Here, using a number of different cell lines and transient-transfection-transcription assays, we demonstrate that at low levels, wild-type p53 transactivates the human proliferating cell nuclear antigen (PCNA) promoter. When expressed at a similar level, the tumor-derived p53 mutants did not transactivate the PCNA promoter. We identified a p53-binding site on the human PCNA promoter with which p53 interacts sequence specifically. When placed on a heterologous synthetic promoter, the binding site functions as a wild-type p53 response element in either orientation. Deletion of the p53-binding site renders the PCNA promoter p53 nonresponsive, showing that wild-type p53 transactivates the PCNA promoter by binding to the site. At a higher concentration, wild-type p53 inhibits the PCNA promoter but p53 mutants activate. Transactivation by p53 mutants does not require the p53-binding site. These observations suggest that moderate elevation of the cellular wild-type p53 level induces PCNA production to help in DNA repair.