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Title: APAF-1 is a transcriptional target of p53 in DNA damage-induced apoptosis. Author: Robles AI, Bemmels NA, Foraker AB, Harris CC. Journal: Cancer Res; 2001 Sep 15; 61(18):6660-4. PubMed ID: 11559530. Abstract: The expression of genes involved in p53-mediated apoptosis was studied using cDNA microarray after treating isogenic cell lines with either ionizing radiation or doxorubicin. Most of the known p53 transcriptional activation target genes clustered in a functional category defined by early and p53-dependent induction, regardless of the type of stress. Apoptotic protease activating factor-1 (APAF-1) emerged from this analysis as a novel p53 target gene. Genomic sequences upstream of the APAF-1 transcription start site contain a classic p53-responsive element that bound to p53. Consistently, p53 directly induced APAF-1 gene expression. Furthermore, DNA damage-mediated induction of APAF-1 mRNA and protein expression, accompanied by apoptosis, were strictly dependent on wild-type p53 function. These data are consistent with the hypothesis that APAF-1 is an essential downstream effector of p53-mediated apoptosis.[Abstract] [Full Text] [Related] [New Search]