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. 2006 Sep 1;23(5):757-64.
doi: 10.1016/j.molcel.2006.07.010.

Wip1 phosphatase modulates ATM-dependent signaling pathways

Sathyavageeswaran Shreeram  1 , Oleg N Demidov, Weng Kee Hee, Hiroshi Yamaguchi, Nobuyuki Onishi, Calvina Kek, Oleg N Timofeev, Crissy Dudgeon, Albert J Fornace, Carl W Anderson, Yasuhiro Minami, Ettore Appella, Dmitry V Bulavin
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Free article

Wip1 phosphatase modulates ATM-dependent signaling pathways

Sathyavageeswaran Shreeram et al. Mol Cell. .
Free article

Abstract

Deletion of Ppm1d, the gene encoding the Wip1 phosphatase, renders cells resistant to transformation and mice resistant to tumor development. Here, we report that deficiency of Wip1 resulted in activation of the ataxia-telangiectasia mutated (ATM) kinase. In turn, overexpression of Wip1 was sufficient to reduce activation of the ATM-dependent signaling cascade after DNA damage. Wip1 dephosphorylated ATM Ser1981, a site critical for ATM monomerization and activation, and was critical for resetting ATM phosphorylation as cells repaired damaged DNA. We propose that the Wip1 phosphatase is an integral component of an ATM-dependent signaling pathway.

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