Requirement of protein phosphatase 5 in DNA-damage-induced ATM activation

被引：129

作者：

Ali, A

Zhang, J

Bao, SD

Liu, I

Otterness, D

Dean, NM

Abraham, RT

Wang, XF ^{[1
]}

机构：

[1] Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA

[2] Burnham Inst, La Jolla, CA 92037 USA

[3] ISIS Pharmaceut, Gene Trove, Dept Funct Genom, Carlsbad, CA 92008 USA

来源：

GENES & DEVELOPMENT | 2004年 / 18卷 / 03期

关键词：

DNA damage; cell cycle checkpoint; ATM; protein phosphatase 5;

D O I：

10.1101/gad.1176004

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

The checkpoint kinase ATM is centrally involved in the cellular response to DNA double-strand breaks. However, the mechanism of ATM activation during genotoxic stress is only partially understood. Here we report a direct regulatory linkage between the protein serine-threonine phosphatase 5 (PP5) and ATM. PP5 interacts with ATM in a DNA-damage-inducible manner. Reduced expression of PP5 attenuated DNA-damage-induced activation of ATM. Expression of a catalytically inactive PP5 mutant inhibited the phosphorylation of ATM substrates and the autophosphorylation of ATM on Ser 1981, and caused an S-phase checkpoint defect in DNA-damaged cells. Together our findings indicate that PP5 plays an essential role in the activation and checkpoint signaling functions of ATM in cells that have suffered DNA double-strand breaks.

引用

页码：249 / 254

页数：6

共 29 条

[1] Cell cycle checkpoint signaling through the ATM and ATR kinases [J].