CDC2 is down-regulated by ionizing radiation in a p53-dependent manner.

The mammalian cellular response to ionizing radiation results in delays in progression through the cell cycle at several checkpoints and includes alterations in the activity of cyclin-dependent kinases. The product of the CDC2 gene is a key kinase involved in cell cycle progression. The signaling events that regulate its expression after exposure to DNA-damaging agents are not known. We show that cdc2 mRNA and protein are down-regulated after irradiation of normal human and mouse fibroblasts with doses as low as 0.5 Gy. This down-regulation is preceded by induction of p53 and p21W8fl proteins. In human cells in which p53 was nonfunctional and in p53/ or p21 / mouse embryo fibroblasts, no effect of ionizing radiation on p34� expression levels was observed. These findings indicate that CDC2 down-regulation after irradiation is p53-dependent and involvesthe cyclin-dependent