Reference : G1 checkpoint failure and increased tumor susceptibility in mice lacking the novel p53 t...
Scientific journals : Article
Human health sciences : Laboratory medicine & medical technology
http://hdl.handle.net/2268/15197
G1 checkpoint failure and increased tumor susceptibility in mice lacking the novel p53 target Ptprv.
English
Doumont, Gilles [> > > >]
Martoriati, Alain [> > > >]
Beekman, Chantal [> > > >]
Bogaerts, Sven [> > > >]
Mee, Patrick J [> > > >]
Bureau, Fabrice mailto [Université de Liège - ULg > Département de sciences fonctionnelles > GIGA-R : Biochimie et biologie moléculaire >]
Colombo, Emanuela [> > > >]
Alcalay, Myriam [> > > >]
Bellefroid, Eric [> > > >]
Marchesi, Francesco [> > > >]
Scanziani, Eugenio [> > > >]
Pelicci, Pier Giuseppe [> > > >]
Marine, Jean-Christophe [> > > >]
2005
EMBO Journal
Oxford University Press
24
17
3093-3103
Yes (verified by ORBi)
International
0261-4189
1460-2075
Oxford
United Kingdom
[en] DNA damage ; growth arrest ; p53 ; Ptprv ; skin
[en] 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.
Researchers ; Professionals
http://hdl.handle.net/2268/15197
10.1038/sj.emboj.7600769

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