Regulation of Claspin degradation by the ubiquitin-proteo some pathway during the cell cycle and in response to ATR-dependent checkpoint activation
Regulation of Claspin degradation by the ubiquitin-proteo some pathway during the cell cycle and in response to ATR-dependent checkpoint activation
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DOI：
10.1016/j.febslet.2006.06.071
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发表时间：
2006-07-24
期刊：
影响因子：
3.5
通讯作者：
Clarke, Paul R.
中科院分区：
文献类型：
--
作者：
Bennett, Lara N.;Clarke, Paul R.
Claspin参与DNA复制过程中atr依赖性Chk1的激活和对DNA损伤的反应。我们发现，在细胞周期中，泛素-蛋白体途径调控了Claspin的降解。Claspin在s期稳定，但在有丝分裂时突然降解，并且在早期G细胞中不存在，在早期G细胞中，ATR对Chk1的磷酸化被取消。在对羟基脲、UV或aphidicolin的反应中，Claspin在chk1结合域被磷酸化，其蛋白水平以atr依赖的方式增加。因此，Chk1途径是通过Claspin的磷酸化及其受控降解来调节的。(c) 2006年欧洲生化学会联合会。Elsevier B.V.版权所有。
Claspin is involved in ATR-dependent activation of Chk1 during DNA replication and in response to DNA damage. We show that degradation of Claspin by the ubiquitin-proteosome pathway is regulated during the cell cycle. Claspin is stabilized in S-phase but is abruptly degraded in mitosis and is absent from early G, cells in which the phosphorylation of Chk1 by ATR is abrogated. In response to hydroxyurea, UV or aphidicolin, Claspin is phosphorylated in the Chk1-binding domain and its protein levels are increased in an ATR-dependent manner. Thus, the Chk1 pathway is regulated through both phosphorylation of Claspin and its controlled degradation. (c) 2006 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.