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Molecular and Cellular Biology, March 2008, p. 1528-1540, Vol. 28, No. 5
0270-7306/08/$08.00+0     doi:10.1128/MCB.02061-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Repression of PTEN Phosphatase by Snail1 Transcriptional Factor during Gamma Radiation-Induced Apoptosis{triangledown}

Maria Escrivà,1,2,{dagger} Sandra Peiró,1,{dagger} Nicolás Herranz,1 Patricia Villagrasa,1,3 Natàlia Dave,1 Bàrbara Montserrat-Sentís,1 Stephen A. Murray,4 Clara Francí,1 Thomas Gridley,4 Ismo Virtanen,5 and Antonio García de Herreros1,2*

Programa de Recerca en Càncer, IMIM-Hospital del Mar, Barcelona, Spain,1 Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain,2 Unitat de Biofísica, Departament de Bioquímica i Biologia Molecular, Facultat de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain,3 Jackson Laboratories, Bar Harbor, Maine,4 Institute of Biomedicine/Anatomy, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland5

Received 16 November 2007/ Returned for modification 11 December 2007/ Accepted 18 December 2007

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 {gamma} 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 {gamma} 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 {gamma} 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.


* Corresponding author. Mailing address: Institut Municipal d'Investigació Mèdica, Parc de Recerca Biomèdica de Barcelona, c/Dr. Aiguader 88, E-08003 Barcelona, Spain. Phone: 34-93-316-0433. Fax: 34-93-316-0410. E-mail: agarcia{at}imim.es

{triangledown} Published ahead of print on 2 January 2008.

{dagger} Both authors made equivalent contributions and should be considered first authors.


Molecular and Cellular Biology, March 2008, p. 1528-1540, Vol. 28, No. 5
0270-7306/08/$08.00+0     doi:10.1128/MCB.02061-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.




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