DNA damage-induced activation of p53 by the checkpoint kinase Chk2

被引：1004

作者：

Hirao, A

Kong, YY

Matsuoka, S

Wakeham, A

Ruland, J

Yoshida, H

Liu, D

Elledge, SJ

Mak, TW

机构：

[1] Univ Toronto, Ontario Canc Inst, Amgen Inst, Toronto, ON M5G 2C1, Canada

[2] Univ Toronto, Dept Med Biophys, Toronto, ON M5G 2C1, Canada

[3] Univ Toronto, Dept Immunol, Toronto, ON M5G 2C1, Canada

[4] Baylor Coll Med, Howard Hughes Med Inst, Verna & Marrs Mclean Dept Biochem & Mol Biol, Houston, TX 77030 USA

[5] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA

来源：

SCIENCE | 2000年 / 287卷 / 5459期

关键词：

D O I：

10.1126/science.287.5459.1824

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：

Chk2 is a protein kinase that is activated in response to DNA damage and may regulate cell cycle arrest. We generated Chk2-deficient mouse cells by gene targeting. Chk2(-/-) embryonic stem cells failed to maintain gamma-irradiation-induced arrest in the Ci phase of the cell cycle. Chk2(-/-) thymocytes were resistant to DNA damage-induced apoptosis. Chk2(-/-) cells were defective for p53 stabilization and for induction of p53-dependent transcripts such as p21 in response to gamma irradiation. Reintroduction of the Chk2 gene restored p53-dependent transcription in response to gamma irradiation. Chk2 directly phosphorylated p53 on serine 20, which is known to interfere with Mdm2 binding. This provides a mechanism for increased stability of p53 by prevention of ubiquitination in response to DNA damage.

引用

页码：1824 / 1827

页数：4

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