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G1 checkpoint failure and increased tumor susceptibility in mice lacking the novel p53 target Ptprv.
- Source :
-
EMBO Journal . 9/7/2005, Vol. 24 Issue 17, p3093-3103. 11p. - Publication Year :
- 2005
-
Abstract
- In response to DNA damage, p53 activates a G1 cell cycle checkpoint, in part through induction of the cyclin-dependent kinase inhibitor p21(Waf1/Cip1). Here we report the identification of a new direct p53 target, Ptprv (or ESP), encoding a transmembrane tyrosine phosphatase. Ptprv transcription is dramatically and preferentially increased in cultured cells undergoing p53-dependent cell cycle arrest, but not in cells undergoing p53-mediated apoptosis. This observation was further confirmed in vivo using a Ptprv null-reporter mouse line. A p53-responsive element is present in the Ptprv promoter and p53 is recruited to this site in vivo. Importantly, while p53-dependent apoptosis is intact in mice lacking Ptprv, Ptprv-null fibroblasts and epithelial cells of the small intestine are defective in G1 checkpoint control. Thus, Ptprv is a new direct p53 target and a key mediator of p53-induced cell cycle arrest. Finally, Ptprv loss enhances the formation of epidermal papillomas after exposure to chemical carcinogens, suggesting that Ptprv acts to suppress tumor formation in vivo. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 02614189
- Volume :
- 24
- Issue :
- 17
- Database :
- Academic Search Index
- Journal :
- EMBO Journal
- Publication Type :
- Academic Journal
- Accession number :
- 18147436
- Full Text :
- https://doi.org/10.1038/sj.emboj.7600769