AP2 alpha alters the transcriptional activity and stability of p53

作者：Stabach PR; Thiyagarajan MM; Woodfield GW; Weigel RJ^*

来源：Oncogene, 2006, 25(15): 2148-2159.

DOI：10.1038/sj.onc.1209250

• AP2 alpha
• AP-2
• p53
• transcription
• stability
• p21

AP2 alpha and p53 form nuclear complexes that establish a functional partnership, which regulates the expression of certain genes involved in cell growth and metastasis. The growth effects of AP2 alpha are mediated through p21(WAF1/CIP1) and the ability for AP2 alpha to coactivate p21 requires p53. Herein, we have localized the AP2-binding region of p53 to amino acids 305-375. Analysis of 26 distinct p53 alleles established a correlation between AP2a binding and transcriptional coactivation. The L350P point mutation was the only nonbinding allele that retained normal transcriptional activity by reporter assay. Although both wild-type and L350P alleles facilitated binding of AP2 alpha to the p21 promoter, the L350P allele was significantly reduced in its ability to induce the endogenous p21 gene, demonstrating a striking difference in activity comparing reporter assays with activation of endogenous p53 target genes. Interestingly, expression of AP2 in the absence of radiation repressed p53-mediated induction of p21 and this effect was explained by a reduction in p53 stability induced by AP2 alpha overexpression. We conclude that AP2 alpha has competing effects on p53 activity through coactivation and decreased stability. These findings may provide a mechanism to account for the discrepancies reported for the association between AP2 and p21 expression in tumor tissue.

• 出版日期2006-4