AP2α alters the transcriptional activity and stability of p53

P. R STABACH; M. M THIYAGARAJAN; G. W WOODFIELD; R J Weigel

doi:10.1038/sj.onc.1209250

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AP2α alters the transcriptional activity and stability of p53

Journal article

Peer reviewed

AP2α alters the transcriptional activity and stability of p53

P. R STABACH, M. M THIYAGARAJAN, G. W WOODFIELD and R J Weigel

Oncogene, Vol.25(15), pp.2148-2159

2006

DOI: 10.1038/sj.onc.1209250

PMID: 16288208

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Abstract

AP2alpha 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 AP2alpha are mediated through p21WAF1/CIP1 and the ability for AP2alpha 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 AP2alpha 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 AP2alpha 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 AP2alpha overexpression. We conclude that AP2alpha 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.

Cell Physiology

Molecular Genetics

Fundamental and applied biological sciences. Psychology

Transcription. Transcription factor. Splicing. Rna processing

Biological and medical sciences

Molecular and cellular biology

Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes

Details

Title: Subtitle: AP2α alters the transcriptional activity and stability of p53
Creators: P. R STABACH - Department of Surgery, Thomas Jefferson University, Philadelphia, PA, United States
M. M THIYAGARAJAN - Department of Surgery, Thomas Jefferson University, Philadelphia, PA, United States
G. W WOODFIELD - Department of Surgery, Thomas Jefferson University, Philadelphia, PA, United States
R J Weigel - Department of Surgery, Thomas Jefferson University, Philadelphia, PA, United States
Resource Type: Journal article
Publication Details: Oncogene, Vol.25(15), pp.2148-2159
DOI: 10.1038/sj.onc.1209250
PMID: 16288208
NLM abbreviation: Oncogene
ISSN: 0950-9232
eISSN: 1476-5594
Publisher: Nature Publishing; Basingstoke
Language: English
Date published: 2006
Academic Unit: Molecular Physiology and Biophysics; Anatomy and Cell Biology; Surgery; Biochemistry and Molecular Biology
Record Identifier: 9984024414902771

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