WILD-TYPE HUMAN P53 TRANSACTIVATES THE HUMAN PROLIFERATING CELL NUCLEAR ANTIGEN PROMOTER

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-transcripti on assays, we demonstrate that at low levels, wild-type p53 transactiv ates the human proliferating cell nuclear antigen (PCNA) promoter. Whe n expressed at a similar level, the tumor-derived p53 mutants did not transactivate the PCNA promoter. We identified a p53-binding site on t he human PCNA promoter with which p53 interacts sequence specifically. When placed on a heterologous synthetic promoter, the binding site fu nctions as a wild-type p53 response element in either orientation. Del etion of the p53-binding site renders the PCNA promoter p53 nonrespons ive, showing that wild-type p53 transactivates the PCNA promoter by bi nding to the site. At a higher concentration, wild-type p53 inhibits t he PCNA promoter but p53 mutants activate. Transactivation by p53 muta nts does not require the p53-binding site. These observations suggest that moderate elevation of the cellular wild-type p53 level induces PC NA production to help in DNA repair.