The tumor suppressor p53 can both stimulate and inhibit ultraviolet light-induced apoptosis

We have previously shown that the tumor suppressor p53 can play a protectiv e role against UV-induced apoptosis in human fibroblasts. In the present st udy, we investigated whether the protective function of p53 expression is e stablished before or after UV irradiation. Using a stable human cell line e xpressing a murine temperature-sensitive p53 in which p53 function could be tightly and reversibly regulated, we found that functional p53 stimulated the induction of apoptosis when expressed for as little as 4-12 h after UV irradiation and that this induction was not dependent on de novo protein sy nthesis. In contrast, expression of p53 for 12 h or more before UV irradiat ion reduced the extent of apoptosis even when functional p53 expression was maintained after irradiation. The protection conferred by p53 required ong oing protein synthesis and correlated with enhanced recovery of mRNA synthe sis. Together, these results suggest that p53 induces distinct proapoptotic and antiapoptotic signals and that these opposing activities can be separa ted both temporally and by their requirement for de novo protein synthesis. These findings may have important implications for the refinement of gene therapy approaches combining p53 with pharmacological agents that target tr anscription or translation.