Activating enhancer-binding protein 2a (AP-2a) and activating enhancer-binding protein 2c (AP-2c) are transcription factors that bind GC-rich consensus sequences and regulate the expression of many downstream genes. AP-2a and AP-2c interact with p53 both physically and functionally. Expression microarray results in human breast carcinoma cells with forced p53 expression revealed AP-2c as a putative transcriptional target of p53. To confirm and extend these findings we measured the effects of forced p53 expression in human breast carcinoma cells by real-time reverse transcription-PCR, Western blotting, electrophoretic gel mobility shift assays, promoter reporter, chromatin immunoprecipitation and chromatin accessibility assays. Wild-type p53 expression rapidly induced not only AP-2c but also AP-2a mRNA. The subsequent increase in these proteins led to increased AP-2 DNAbinding and transactivating activity. Candidate p53-binding sites were identified in the AP-2a and AP-2c promoters. p53 binding to these cis-elements in vivo was also observed, together with a relaxation of chromatin structure in these regions. Finally, expression of either AP-2a or c inhibited growth of human breast carcinoma cells in vitro. Taken together, our findings indicate that these AP-2 genes are targets for transcriptional activation by p53 and suggest that AP-2 proteins may mediate some of the downstream effects of p53 expression such as inhibition of proliferation.