APAF-1 is a transcriptional target of p53 in DNA damage-induced apoptosis.
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.
Robles
A I
AI
Laboratory of Human Carcinogenesis, National Cancer Institute, NIH, Bethesda, Maryland 20892-4255, USA.
Bemmels
N A
NA
Foraker
A B
AB
Harris
C C
CC
D017209:Apoptosis / Q000235:genetics*; D053477:Apoptotic Protease-Activating Factor 1; D002460:Cell Line; D015179:Colorectal Neoplasms / Q000235:genetics / Q000473:pathology; D004249:DNA Damage; D020869:Gene Expression Profiling; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D005810:Multigene Family; D020411:Oligonucleotide Array Sequence Analysis; D011506:Proteins / Q000235:genetics*; D015533:Transcriptional Activation / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
C506592:APAF1 protein, human; D053477:Apoptotic Protease-Activating Factor 1; D011506:Proteins; D016159:Tumor Suppressor Protein p53