AP-2alpha and AP-2gamma are transcriptional targets of p53 in human breast carcinoma cells.
Oncogene
; 25(39): 5405-15, 2006 Aug 31.
Article
de En
| MEDLINE
| ID: mdl-16636674
ABSTRACT
Activating enhancer-binding protein 2alpha (AP-2alpha) and activating enhancer-binding protein 2gamma (AP-2gamma) are transcription factors that bind GC-rich consensus sequences and regulate the expression of many downstream genes. AP-2alpha and AP-2gamma interact with p53 both physically and functionally. Expression microarray results in human breast carcinoma cells with forced p53 expression revealed AP-2gamma 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-2gamma but also AP-2alpha 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-2alpha and AP-2gamma 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-2alpha or gamma 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.
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Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Gènes p53
/
Facteur de transcription AP-2
Limites:
Female
/
Humans
Langue:
En
Journal:
Oncogene
Sujet du journal:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Année:
2006
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique