Article (Scientific journals)
G1 checkpoint failure and increased tumor susceptibility in mice lacking the novel p53 target Ptprv.
Doumont, Gilles; Martoriati, Alain; Beekman, Chantal et al.
2005In EMBO Journal, 24 (17), p. 3093-3103
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Keywords :
DNA damage; growth arrest; p53; Ptprv; skin
Abstract :
[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.
Disciplines :
Laboratory medicine & medical technology
Author, co-author :
Doumont, Gilles
Martoriati, Alain
Beekman, Chantal
Bogaerts, Sven
Mee, Patrick J
Bureau, Fabrice ;  Université de Liège - ULiège > Département de sciences fonctionnelles > GIGA-R : Biochimie et biologie moléculaire
Colombo, Emanuela
Alcalay, Myriam
Bellefroid, Eric J.
Marchesi, Francesco
Scanziani, Eugenio
Pelicci, Pier Giuseppe
Marine, Jean-Christophe
More authors (3 more) Less
Language :
English
Title :
G1 checkpoint failure and increased tumor susceptibility in mice lacking the novel p53 target Ptprv.
Publication date :
2005
Journal title :
EMBO Journal
ISSN :
0261-4189
eISSN :
1460-2075
Publisher :
Oxford University Press, Oxford, United Kingdom
Volume :
24
Issue :
17
Pages :
3093-3103
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 24 June 2009

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