APAF-1 is a transcriptional target of p53 in DNA damage-induced apoptosis

The expression of genes involved in p53-mediated apoptosis was studied usin g cDNA microarray after treating isogenic cell lines with either ionizing r adiation or doxorubicin. Most of the known p53 transcriptional activation t arget genes clustered in a functional category defined by early and p53-dep endent induction, regardless of the type of stress. Apoptotic protease acti vating factor-1 (APAF-1) emerged from this analysis as a novel p53 target g ene. Genomic sequences upstream of the APAF-1 transcription start site cont ain a classic p53-responsive element that bound to p53. Consistently, p53 d irectly induced APAF-1 gene expression. Furthermore, DNA damage-mediated in duction of APAF-1 mRNA and protein expression, accompanied by apoptosis, we re strictly dependent on wildtype p53 function. These data are consistent w ith the hypothesis that APAF-1 is an essential downstream effector of p53-m ediated apoptosis.