UV-induced interaction between p38 MAPK and p53 serves as a molecular switch in determining cell fate.

p53 plays a fundamental role in the maintenance of genome integrity after DNA damage, deciding whether cells repair and live, or die. However, the rules that govern its choice are largely undiscovered. Here we show that the functional relationship between p38 and p53 is crucial in defining the cell fate after DNA damage. Upon low dose ultraviolet (UV) radiation, p38 and p53 protect the cells from apoptosis separately. Conversely, they function together to favor apoptosis upon high dose UV exposure. Taken together, a UV-induced, dose-dependent interaction between p38 and p53 acts as a switch to determine cell fate.