Abstract
Activating enhancer-binding protein 2α (AP-2α) and activating enhancer-binding protein 2γ (AP-2γ) are transcription factors that bind GC-rich consensus sequences and regulate the expression of many downstream genes. AP-2α and AP-2γ interact with p53 both physically and functionally. Expression microarray results in human breast carcinoma cells with forced p53 expression revealed AP-2γ 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-2γ but also AP-2α mRNA. The subsequent increase in these proteins led to increased AP-2 DNA-binding and transactivating activity. Candidate p53-binding sites were identified in the AP-2α and AP-2γ 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-2α or γ 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.
Original language | English (US) |
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Pages (from-to) | 5405-5415 |
Number of pages | 11 |
Journal | Oncogene |
Volume | 25 |
Issue number | 39 |
DOIs | |
State | Published - Aug 31 2006 |
Keywords
- Activator protein-2
- Breast carcinoma
- Tumor suppressor gene
- p53
ASJC Scopus subject areas
- Molecular Biology
- Genetics
- Cancer Research