G1 checkpoint failure and increased tumor susceptibility in mice lacking the novel p53 target Ptprv

Doumont, G. et al. (2005) G1 checkpoint failure and increased tumor susceptibility in mice lacking the novel p53 target Ptprv. EMBO Journal, 24(17), pp. 3093-3103. (doi: 10.1038/sj.emboj.7600769)

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Marchesi, Dr Francesco
• Authors: Doumont, G., Martoriati, A., Beekman, C., Bogaerts, S., Mee, P.J., Bureau, F., Colombo, E., Alcalay, M., Bellefroid, E., Marchesi, F., Scanziani, E., Pelicci, P.G., and Marine, J.-C.
• College/School: College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
• Journal Name: EMBO Journal
• ISSN: 0261-4189
• ISSN (Online): 1460-2075