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

被引：117

作者：

Shreeram, Sathyavageeswaran

Hee, Weng Kee

Demidov, Oleg N.

Kek, Calvina

Yamaguchi, Hiroshi

Fornace, Albert J., Jr.

Anderson, Carl W.

Appella, Ettore

Bulavin, Dmitry V. ^{[1
]}

机构：

[1] Inst Cell & Mol Biol, Singapore 138673, Singapore

[2] NCI, Cell Biol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA

[3] Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA 02115 USA

[4] Brookhaven Natl Lab, Dept Biol, Upton, NY 11973 USA

来源：

JOURNAL OF EXPERIMENTAL MEDICINE | 2006年 / 203卷 / 13期

关键词：

D O I：

10.1084/jem.20061563

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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 E mu-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.

引用

收藏

页码：2793 / 2799

页数：7

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