AP-2α and AP-2γ are transcriptional targets of p53 in human breast carcinoma cells

H. Li, G. S. Watts, M. M. Oshiro, B. W. Futscher, F. E. Domann

Research output: Contribution to journalArticle

22 Scopus citations

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 languageEnglish (US)
Pages (from-to)5405-5415
Number of pages11
JournalOncogene
Volume25
Issue number39
DOIs
StatePublished - Aug 31 2006

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Keywords

  • Activator protein-2
  • Breast carcinoma
  • Tumor suppressor gene
  • p53

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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