Title: G1 checkpoint failure and increased tumor susceptibility in mice lacking the novel p53 target Ptprv
Authors: Doumont, G
Martoriati, A
Beekman, C
Bogaerts, S
Mee, PJ
Bureau, F
Colombo, E
Alcalay, M
Bellefroid, E
Marchesi, F
Scanziani, E
Pelicci, PG
Marine, Chris # ×
Issue Date: Sep-2005
Publisher: Nature Publishing Group
Series Title: EMBO Journal vol:24 issue:17 pages:3093-3103
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.
ISSN: 0261-4189
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Non-KU Leuven Association publications
× corresponding author
# (joint) last author

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