Fig. 8. p53 and ACER2 mediate DNA damage response through SPH, S1P, and ceramides.

High-grade DNA damage (red) causes a hyperactivation of the p53/ACER2 pathway, resulting in the dominance of the pro-death signal of SPH over the pro-proliferative and pro-survival of S1P and thereby PCD. Low-grade DNA damage (blue) triggers a moderate activation of the p53/ACER2 pathway, resulting in a balance of the pro-death signal of SPH and pro-senescence signal of ceramides with the pro-proliferative and pro-survival signals of S1P and thereby cell cycle arrest and senescence