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

Gilles Doumont, Alain Martoriati, Chantal Beekman, Sven Bogaerts, Patrick J. Mee, Fabrice Bureau, Emanuela Colombo, Myriam Alcalay, Eric Bellefroid, Francesco Marchesi, Eugenio Scanziani, Pier Giuseppe Pelicci, Jean Christophe Marine

Research output: Contribution to journalArticle

25 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)3093-3103
Number of pages11
JournalEMBO Journal
Volume24
Issue number17
DOIs
Publication statusPublished - Sep 2005

Fingerprint

Cell Cycle Checkpoints
Tumors
Cells
Cyclin-Dependent Kinase Inhibitor p21
Apoptosis
G1 Phase Cell Cycle Checkpoints
Null Lymphocytes
Papilloma
Phosphoric Monoester Hydrolases
Carcinogens
DNA Damage
Small Intestine
Tyrosine
Cultured Cells
Neoplasms
Fibroblasts
Epithelial Cells
Transcription
DNA

Keywords

  • DNA damage
  • Growth arrest
  • p53
  • Ptprv
  • Skin carcinogenesis

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Doumont, G., Martoriati, A., Beekman, C., Bogaerts, S., Mee, P. J., Bureau, F., ... Marine, J. C. (2005). G1 checkpoint failure and increased tumor susceptibility in mice lacking the novel p53 target Ptprv. EMBO Journal, 24(17), 3093-3103. https://doi.org/10.1038/sj.emboj.7600769

G1 checkpoint failure and increased tumor susceptibility in mice lacking the novel p53 target Ptprv. / Doumont, Gilles; Martoriati, Alain; Beekman, Chantal; Bogaerts, Sven; Mee, Patrick J.; Bureau, Fabrice; Colombo, Emanuela; Alcalay, Myriam; Bellefroid, Eric; Marchesi, Francesco; Scanziani, Eugenio; Pelicci, Pier Giuseppe; Marine, Jean Christophe.

In: EMBO Journal, Vol. 24, No. 17, 09.2005, p. 3093-3103.

Research output: Contribution to journalArticle

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, JC 2005, 'G1 checkpoint failure and increased tumor susceptibility in mice lacking the novel p53 target Ptprv', EMBO Journal, vol. 24, no. 17, pp. 3093-3103. https://doi.org/10.1038/sj.emboj.7600769
Doumont G, Martoriati A, Beekman C, Bogaerts S, Mee PJ, Bureau F et al. G1 checkpoint failure and increased tumor susceptibility in mice lacking the novel p53 target Ptprv. EMBO Journal. 2005 Sep;24(17):3093-3103. https://doi.org/10.1038/sj.emboj.7600769
Doumont, Gilles ; Martoriati, Alain ; Beekman, Chantal ; Bogaerts, Sven ; Mee, Patrick J. ; Bureau, Fabrice ; Colombo, Emanuela ; Alcalay, Myriam ; Bellefroid, Eric ; Marchesi, Francesco ; Scanziani, Eugenio ; Pelicci, Pier Giuseppe ; Marine, Jean Christophe. / G1 checkpoint failure and increased tumor susceptibility in mice lacking the novel p53 target Ptprv. In: EMBO Journal. 2005 ; Vol. 24, No. 17. pp. 3093-3103.
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