PTPRV is a key mediator of p53-induced cell cycle exit.
The p53 tumor suppressor functions as a sequence-specific DNA-binding transcription factor that promotes antiproliferative responses, including cell cycle checkpoints, cellular senescence and apoptosis. The precise nature of the p53 transcriptional programs and the complex mechanisms that govern whether or not a cell dies in response to p53 activation remain elusive. We have recently reported the identification of a new direct p53 target, Ptprv, encoding a transmembrane tyrosine phosphatase. Ptprv expression is dramatically and preferentially increased in cells undergoing p53-dependent cell cycle exit, but not in cells undergoing p53-mediated apoptosis. Importantly, while p53-induced apoptosis is intact in mice lacking Ptprv, Ptprv-null cells are defective in G1 checkpoint control. In addition, we report herein that Ptprv is induced at high cell density and mediates contact inhibition of cell growth. Together, the data suggest that Ptprv is a potent inhibitor of cell proliferation and a critical mediator of p53-induced cell cycle exit.
Doumont
Gilles
G
Laboratory For Molecular Cancer Biology, Flanders Interuniversity Institute for Biotechnology (VIB), Ghent University, Ghent, Belgium.
Martoriati
Alain
A
Marine
Jean-Christophe
JC
D000818:Animals; D002453:Cell Cycle; D005347:Fibroblasts / Q000166:cytology; D051379:Mice; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D017027:Protein Tyrosine Phosphatases; C474713:Ptprv protein, mouse; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3