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

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...

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Detalles Bibliográficos
Autores principales: Shreeram, Sathyavageeswaran, Hee, Weng Kee, Demidov, Oleg N., Kek, Calvina, Yamaguchi, Hiroshi, Fornace, Albert J., Anderson, Carl W., Appella, Ettore, Bulavin, Dmitry V.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2006
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2118180/
https://www.ncbi.nlm.nih.gov/pubmed/17158963
http://dx.doi.org/10.1084/jem.20061563
Descripción
Sumario: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.