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

被引：1012
|
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
收藏
页码：1824 / 1827
页数：4
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