Requirement of the prolyl isomerase Pin1 for the replication checkpoint
Requirement of the prolyl isomerase Pin1 for the replication checkpoint
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DOI：
10.1126/science.287.5458.1644
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发表时间：
2000-03-03
期刊：
影响因子：
56.9
通讯作者：
Means, AR
中科院分区：
文献类型：
--
作者：
Winkler, KE;Swenson, KI;Means, AR
多肽基-脯氨酰异构酶Pin1参与调节细胞周期进程。非洲爪哇的DNA复制检查点需要Pin1，在DNA复制抑制剂aphidiclin存在的情况下，去除Pin1的卵提取物不适当地从细胞周期的G(2)期过渡到M期。在耗尽的提取物中加入重组野生型Pin1而不是异构酶失活突变体后，复制检查点功能的这种缺陷被逆转。在没有Pin1的情况下，有丝分裂的过早进入伴随着CDC25的过度磷酸化，CDc2/Cyclin B的激活，以及有丝分裂磷酸蛋白抗体MPM-2识别的表位的产生。因此，PIN1似乎是检查点所必需的，以延迟有丝分裂的开始，以响应不完全复制。
The peptidyl-prolyl isomerase Pin1 has been implicated in regulating cell cycle progression. Pin1 was found to be required for the DNA replication checkpoint in Xenopus laevis, Egg extracts depleted of Pin1 inappropriately transited from the G(2) to the M phase of the cell cycle in the presence of the DNA replication inhibitor aphidicolin. This defect in replication checkpoint function was reversed after the addition of recombinant wild-type Pin1, but not an isomerase-inactive mutant, to the depleted extract. Premature mitotic entry in the absence of Pin1 was accompanied by hyperphosphorylation of Cdc25, activation of Cdc2/cyclin B, and generation of epitopes recognized by the mitotic phosphoprotein antibody, MPM-2. Therefore, Pin1 appears to be required for the checkpoint delaying the onset of mitosis in response to incomplete replication.