G1 checkpoint failure and increased tumor susceptibility in mice lacking the novel p53 target Ptprv
Articolo
Data di Pubblicazione:
2005
Citazione:
G1 checkpoint failure and increased tumor susceptibility in mice lacking the novel p53 target Ptprv / G. Doumont, A. Martoriati, C. Beekman, S. Bogaerts, P. Mee, F. Bureau, E. Colombo, M. Alcalay, E. Bellefroid, F. Marchesi, E. Scanziani, P. Pelicci, J. Marine. - In: EMBO JOURNAL. - ISSN 0261-4189. - 24:17(2005), pp. 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
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
DNA damage ; growth arrest ; p53 ; Ptprv ; skin carcinogenesis
Elenco autori:
G. Doumont, A. Martoriati, C. Beekman, S. Bogaerts, P. Mee, F. Bureau, E. Colombo, M. Alcalay, E. Bellefroid, F. Marchesi, E. Scanziani, P. Pelicci, J. Marine
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