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p53 is a major component of the transcriptional and apoptotic program regulated by PI 3-kinase/Akt/GSK3 signaling.

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Year: 2011 Volume: 2

Year: 2010 Volume: 1

p53 is a major component of the transcriptional and apoptotic program regulated by PI 3-kinase/Akt/GSK3 signaling.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Nayak, G. Cooper, G. M.
Description	Country affiliation: United States Author Affiliation: Nayak G ( Department of Biology, Boston University, Boston, MA 02215, USA.)
Abstract	The phosphatidylinositol (PI) 3-kinase/Akt signaling pathway has a prominent role in cell survival and proliferation, in part, by regulating gene expression at the transcriptional level. Previous work using global expression profiling identified FOXOs and the E-box-binding transcription factors MITF and USF1 as key targets of PI 3-kinase signaling that lead to the induction of proapoptotic and cell cycle arrest genes in response to inhibition of PI 3-kinase. In this study, we investigated the role of p53 downstream of PI 3-kinase signaling by analyzing the effects of inhibition of PI 3-kinase in Rat-1 cells, which have wild-type p53, compared with Rat-1 cells expressing a dominant-negative p53 mutant. Expression of dominant-negative p53 conferred partial resistance to apoptosis induced by inhibition of PI 3-kinase. Global gene expression profiling combined with computational and experimental analysis of transcription factor binding sites demonstrated that p53, along with FOXO, MITF and USF1, contributed to gene induction in response to PI 3-kinase inhibition. Activation of p53 was mediated by phosphorylation of the histone acetyltransferase Tip60 by glycogen synthase kinase (GSK) 3, leading to activation of p53 by acetylation. Many of the genes targeted by p53 were also targeted by FOXO and E-box-binding transcription factors, indicating that p53 functions coordinately with these factors to regulate gene expression downstream of PI 3-kinase/Akt/GSK3 signaling.
File Format	HTM / HTML
e-ISSN	20414889
DOI	10.1038/cddis.2012.138
Journal	Cell Death and Disease
Volume Number	3
Language	English
Publisher	Nature Publishing Group
Publisher Date	2012-10-11
Publisher Place	Great Britain (UK)
Access Restriction	Open
Subject Keyword	Proto-oncogene Proteins C-akt Research Support, N.i.h., Extramural Cell Line Phosphorylation Histone Acetyltransferases Signal Transduction Glycogen Synthase Kinase 3 Microphthalmia-associated Transcription Factor Nerve Tissue Proteins Metabolism Upstream Stimulatory Factors Discipline Cell Biology Tumor Suppressor Protein P53 Animals Protein Binding Transcription, Genetic Genetics Phosphatidylinositol 3-kinase Forkhead Transcription Factors Apoptosis
Content Type	Text
Resource Type	Article

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