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Repression of PTEN phosphatase by Snail1 transcriptional factor during gamma radiation-induced apoptosis.
- Source :
-
Molecular and cellular biology [Mol Cell Biol] 2008 Mar; Vol. 28 (5), pp. 1528-40. Date of Electronic Publication: 2008 Jan 02. - Publication Year :
- 2008
-
Abstract
- 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.
- Subjects :
- Animals
Cell Line
Cell Line, Tumor
Chromatin Immunoprecipitation
DNA Damage
DNA, Complementary
Dogs
G2 Phase
Genes, Reporter
Humans
Luciferases, Firefly analysis
Luciferases, Firefly metabolism
Luciferases, Renilla analysis
Luciferases, Renilla metabolism
Luminescent Agents metabolism
Pancreatic Neoplasms pathology
Promoter Regions, Genetic
Protein Synthesis Inhibitors pharmacology
Proto-Oncogene Proteins c-akt metabolism
Puromycin pharmacology
RNA, Messenger metabolism
RNA, Small Interfering pharmacology
Selection, Genetic
Snail Family Transcription Factors
Time Factors
Transcription Factors genetics
Transcription Factors pharmacology
Transfection
Apoptosis radiation effects
Gamma Rays
Gene Expression Regulation
PTEN Phosphohydrolase antagonists & inhibitors
Transcription Factors metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1098-5549
- Volume :
- 28
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Molecular and cellular biology
- Publication Type :
- Academic Journal
- Accession number :
- 18172008
- Full Text :
- https://doi.org/10.1128/MCB.02061-07