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J Exp Med. 2006 Dec 25;203(13):2793-9. Epub 2006 Dec 11.

Regulation of ATM/p53-dependent suppression of myc-induced lymphomas by Wip1 phosphatase.

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1
Institute of Molecular and Cell Biology, Singapore, 138673.

Abstract

The ataxia telangiectasia mutated (ATM) kinase is a key tumor suppressor that regulates numerous cell cycle checkpoints as well as apoptosis. Here, we report that ATM is a critical player in the regulation of apoptosis and lymphomagenesis in the presence of c-myc. In turn, deletion of the inhibitory ATM phosphatase, Wip1, results in ATM up-regulation and suppression of Emicro-myc-induced B cell lymphomas. Using mouse genetic crosses, we show that the onset of myc-induced lymphomas is dramatically delayed in Wip1-null mice in an ATM- and p53-, but not p38 MAPK- or Arf-, dependent manner. We propose that Wip1 phosphatase is critical for regulating the ATM-mediated tumor surveillance network.

PMID:
17158963
PMCID:
PMC2118180
DOI:
10.1084/jem.20061563
[Indexed for MEDLINE]
Free PMC Article

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