TY - JOUR
T1 - Repression of PTEN phosphatase by snail1 transcriptional factor during gamma radiation-induced apoptosis
AU - Escrivà, Maria
AU - Peiró, Sandra
AU - Herranz, Nicolás
AU - Villagrasa, Patricia
AU - Dave, Natàlia
AU - Montserrat-Sentís, Bàrbara
AU - Murray, Stephen A.
AU - Francí, Clara
AU - Gridley, Thomas
AU - Virtanen, Ismo
AU - De Herreros, Antonio García
PY - 2008/1/1
Y1 - 2008/1/1
N2 - The product of the Snail1 gene is a transcriptional repressor required for triggering the epithelial-to-mesenchymal transition. Furthermore, ectopic expression of Snail1 in epithelial cells promotes resistance to apoptosis. In this study, we demonstrate that this resistance to γ radiation-induced apoptosis caused by Snail1 is associated with the inhibition of PTEN phosphatase. In MDCK cells, mRNA levels of the p53 target gene PTEN are induced after γ radiation; the transfection of Snail1 prevents this up-regulation. Decreased mRNA levels of PTEN were also detected in RWP-1 cells after the ectopic expression of this transcriptional factor. Snail1 represses and associates to the PTEN promoter as detected both by the electrophoretic mobility shift assay and chromatin immunoprecipitation experiments performed with either endogenous or ectopic Snail1. The binding of Snail1 to the PTEN promoter increases after γ radiation, correlating with the stabilization of Snail1 protein, and prevents the association of p53 to the PTEN promoter. These results stress the critical role of Snail1 in the control of apoptosis and demonstrate the regulation of PTEN phosphatase by this transcriptional repressor. Copyright © 2008, American Society for Microbiology. All Rights Reserved.
AB - The product of the Snail1 gene is a transcriptional repressor required for triggering the epithelial-to-mesenchymal transition. Furthermore, ectopic expression of Snail1 in epithelial cells promotes resistance to apoptosis. In this study, we demonstrate that this resistance to γ radiation-induced apoptosis caused by Snail1 is associated with the inhibition of PTEN phosphatase. In MDCK cells, mRNA levels of the p53 target gene PTEN are induced after γ radiation; the transfection of Snail1 prevents this up-regulation. Decreased mRNA levels of PTEN were also detected in RWP-1 cells after the ectopic expression of this transcriptional factor. Snail1 represses and associates to the PTEN promoter as detected both by the electrophoretic mobility shift assay and chromatin immunoprecipitation experiments performed with either endogenous or ectopic Snail1. The binding of Snail1 to the PTEN promoter increases after γ radiation, correlating with the stabilization of Snail1 protein, and prevents the association of p53 to the PTEN promoter. These results stress the critical role of Snail1 in the control of apoptosis and demonstrate the regulation of PTEN phosphatase by this transcriptional repressor. Copyright © 2008, American Society for Microbiology. All Rights Reserved.
U2 - 10.1128/MCB.02061-07
DO - 10.1128/MCB.02061-07
M3 - Article
SN - 0270-7306
VL - 28
SP - 1528
EP - 1540
JO - Molecular and Cellular Biology
JF - Molecular and Cellular Biology
IS - 5
ER -