期刊
ONCOGENE
卷 28, 期 10, 页码 1366-1378出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/onc.2008.477
关键词
checkpoint; CHK2; TTK/hMps1
资金
- Academia Sinica
- National Science Council of Taiwan
Cell cycle progression is monitored constantly to ensure faithful passage of genetic codes and genome stability. We have demonstrated previously that, upon DNA damage, TTK/hMps1 activates the checkpoint kinase CHK2 by phosphorylating CHK2 at Thr68. However, it remains to be determined whether and how TTK/hMps1 responds to DNA damage. In this report, we present evidence that TTK/hMps1 can be induced by DNA damage in normal human. broblasts. Interestingly, the induction depends on CHK2 because CHK2-targeting small interfering RNA or a CHK2 inhibitor abolishes the increase. Such induction is mediated through phosphorylation of TTK/hMps1 at Thr288 by CHK2 and requires the CHK2 SQ/TQ cluster domain/forkhead-associated domain. In cells, TTK/hMps1 phosphorylation at Thr288 is induced by DNA damage and forms nuclear foci, which colocalize partially with c-H2AX. Reexpression of TTK/hMps1 T288A mutant in TTK/hMps1-knockdown cells causes a defect in G2/M arrest, suggesting that phosphorylation at this site participates in the proper checkpoint execution. Our study uncovered a regulatory loop between TTK/hMps1 and CHK2 whereby DNA damage-activated CHK2 may facilitate the stabilization of TTK/hMps1, therefore maintaining the checkpoint control.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据