Presentation Abstract

Abstract Number: 4211
Presentation Title: p85alpha mediates p53 K370 acetylation by p300 and regulates its promoter-specific transactivity in the cellular UVB response
Presentation Time: Tuesday, Apr 05, 2011, 1:00 PM - 5:00 PM
Location: Exhibit Hall A4-C, Poster Section 16
Poster Section: 16
Poster Board Number: 19
Author Block: Lun Song1, Ming Gao2, Wen Dong2, Meiru Hu2, Jingxia Li1, Xiaoyan Shi1, Yi Hao2, Yi Li2, Chuanshu Huang1. 1NYU School of Medicine, Tuxedo, NY; 2Beijing Institute of Basic Medical Sciences, Beijing, China
Abstract Body: Inducible acetylation of p53 at lysine residues has a great impact on regulating the transactivation of this protein, which is associated with cell growth arrest and/or apoptosis under various stress conditions. However, the factor(s) for regulating p53 acetylation remains largely unknown. In the current study, we have shown that p85α, the regulatory subunit of PI-3K, plays a critical role in mediating p53 acetylation and promoter-specific transactivation in the UVB response. Depletion of p85α in mouse embryonic fibroblasts (MEFs) significantly impairs UVB-induced apoptosis as well as p53 transactivation and acetylation at Lys370 (Lys373 of human p53); however, the accumulation, nuclear translocation and phosphorylation of p53 are not affected. Interestingly, p85α binds to p300, promotes the p300-p53 interaction and the subsequent recruitment of the p53/p300 complex to the promoter region of the specific p53 target gene in response to UVB irradiation. Moreover, ablation of p53 acetylation at Lys370 by site-directed mutagenesis dramatically suppresses UVB-induced expression of the specific p53-responsive gene as well as cell apoptosis. Therefore, we conclude that p85α is a novel regulator of p53-mediated response under certain stress conditions, and targeting the p85α-dependent p53 pathway may be promising for cancer therapy.
Key Words: acetylation/ p85α/ p53/ p300/UVB radiation