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 phosphatidylinositol-3-kinase, 
has a critical role in mediating p53 acetylation and promoter-specific 
transactivation in the ultraviolet B (UVB) response. Depletion of p85α in mouse 
embryonic fibroblasts 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.