Activation of the ATM kinase by ionizing radiation and phosphorylation of p53

被引：1684

作者：

Canman, CE

Lim, DS

Cimprich, KA

Taya, Y

Tamai, K

Sakaguchi, K

Appella, E

Kastan, MB

Siliciano, JD

机构：

[1] Johns Hopkins Univ, Sch Med, Ctr Oncol, Baltimore, MD 21205 USA

[2] Stanford Univ, Sch Med, Dept Mol Pharmacol, Stanford, CA 94305 USA

[3] Natl Canc Ctr, Res Inst, Chuo Ku, Tokyo 104, Japan

[4] MBL Co Ltd, Ina Labs, Nagano 396, Japan

[5] NIH, Cell Biol Lab, Bethesda, MD 20892 USA

来源：

SCIENCE | 1998年 / 281卷 / 5383期

关键词：

D O I：

10.1126/science.281.5383.1677

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The p53 tumor suppressor protein is activated and phosphorylated on serine-15 in response to various DNA damaging agents. The gene product mutated in ataxia telangiectasia, ATM, acts upstream of p53 in a signal transduction pathway initiated by ionizing radiation. Immunoprecipitated ATM had intrinsic protein kinase activity and phosphorylated p53 on serine-15 in a manganese-dependent manner. Ionizing radiation, but not ultraviolet radiation, rapidly enhanced this p53-directed kinase activity of endogenous ATM. These observations, along with the fact that phosphorylation of p53 on serine-15 in response to ionizing radiation is reduced in ataxia telangiectasia cells, suggest that ATM is a protein kinase that phosphorylates p53 in vivo.

引用

页码：1677 / 1679

页数：3

共 25 条

[1] Atm selectively regulates distinct p53-dependent cell-cycle checkpoint and apoptotic pathways [J].