Regulation of ATM/p53-dependent suppression of myc-induced lymphomas by Wip1 phosphatase |
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| Authors: | Shreeram Sathyavageeswaran Hee Weng Kee Demidov Oleg N Kek Calvina Yamaguchi Hiroshi Fornace Albert J Anderson Carl W Appella Ettore Bulavin Dmitry V |
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| Affiliation: | Institute of Molecular and Cell Biology, Singapore, 138673. |
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| 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 Eμ-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. |
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