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.