Mitotic and G(2) checkpoint control: Regulation of 14-3-3 protein binding by phosphorylation of Cdc25C on serine-216
Mitotic and G(2) checkpoint control: Regulation of 14-3-3 protein binding by phosphorylation of Cdc25C on serine-216
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DOI：
10.1126/science.277.5331.1501
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发表时间：
1997-09-05
期刊：
影响因子：
56.9
通讯作者：
PiwnicaWorms, H
中科院分区：
文献类型：
--
作者：
Peng, CY;Graves, PR;PiwnicaWorms, H
人CDC25C是一种双特异性蛋白磷酸酶，它通过去磷酸化蛋白激酶CDC2来控制进入有丝分裂。在整个有丝分裂间期，CDC25C在丝氨酸-216上被磷酸化，并与高度保守和普遍表达的14-3-3蛋白家族的成员结合。阻止丝氨酸-216磷酸化的突变取消了14-3-3结合。这个突变体的条件过表达扰乱了有丝分裂的时间，并允许细胞逃脱由未复制的DNA或辐射诱导的损伤引起的G(2)检查点停滞。Chk1是一种参与DNA损伤检查点反应的裂变型酵母激酶，它在体外将CDC25C磷酸化在丝氨酸-216上。这些结果表明，丝氨酸-216磷酸化和14-3-3结合负性调节CDC25C，并确认CDC25C是人类细胞检查点控制的潜在靶点。
Human Cdc25C is a dual-specificity protein phosphatase that controls entry into mitosis by dephosphorylating the protein kinase Cdc2. Throughout interphase, but not in mitosis, Cdc25C was phosphorylated on serine-216 and bound to members of the highly conserved and ubiquitously expressed family of 14-3-3 proteins. A mutation preventing phosphorylation of serine-216 abrogated 14-3-3 binding. Conditional overexpression of this mutant perturbed mitotic timing and allowed cells to escape the G(2) checkpoint arrest induced by either unreplicated DNA or radiation-induced damage. Chk1, a fission yeast kinase involved in the DNA damage checkpoint response, phosphorylated Cdc25C in vitro on serine-216. These results indicate that serine-216 phosphorylation and 14-3-3 binding negatively regulate Cdc25C and identify Cdc25C as a potential target of checkpoint control in human cells.