Winkler K E, Swenson K I, Kornbluth S, Means A R
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Box 3813, Durham, NC 27710, USA.
Science. 2000 Mar 3;287(5458):1644-7. doi: 10.1126/science.287.5458.1644.
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 G2 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.
肽基脯氨酰异构酶Pin1与调节细胞周期进程有关。研究发现，非洲爪蟾的DNA复制检查点需要Pin1。在存在DNA复制抑制剂阿非迪霉素的情况下，耗尽Pin1的卵提取物会不适当地从细胞周期的G2期过渡到M期。在耗尽的提取物中加入重组野生型Pin1而非异构酶失活突变体后，复制检查点功能的这一缺陷得以逆转。在没有Pin1的情况下过早进入有丝分裂伴随着Cdc25的过度磷酸化、Cdc2/细胞周期蛋白B的激活以及有丝分裂磷蛋白抗体MPM-2识别的表位的产生。因此，Pin1似乎是响应不完全复制而延迟有丝分裂开始的检查点所必需的。
