TRIGGERING OF CYCLIN DEGRADATION IN INTERPHASE EXTRACTS OF AMPHIBIAN EGGS BY CDC2 KINASE
TRIGGERING OF CYCLIN DEGRADATION IN INTERPHASE EXTRACTS OF AMPHIBIAN EGGS BY CDC2 KINASE
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DOI：
10.1038/346379a0
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发表时间：
1990-07-26
期刊：
影响因子：
64.8
通讯作者：
KARSENTI, E
中科院分区：
文献类型：
--
作者：
FELIX, MA;LABBE, JC;KARSENTI, E
早期非洲爪蟾胚胎的细胞周期由S期和M期交替的快速连续组成。这些循环由含有两个亚基的蛋白激酶复合物（cdc 2激酶）的活性控制。其中一个亚基是由裂殖酵母cdc 2+基因的蛙同源物p34 cdc 2（参考文献2）编码的，另一个是细胞周期蛋白3。细胞周期蛋白的浓度遵循周期振荡，因为它们在间期积累，并在有丝分裂期间突然被破坏3。细胞周期蛋白和p34 cdc 2的结合（参考文献4-7）不足以激活cdc 2激酶，然而，p34 cdc 2关键的酪氨酸和苏氨酸残基的去磷酸化是开启其激酶活性所必需的8 -11。因此，cdc 2激酶的活性受翻译和翻译后机制的组合调节。在有丝分裂结束时cdc 2激酶活性的丧失取决于细胞周期蛋白亚基的破坏3，4，12，13。有人认为这种破坏是由cdc 2激酶本身诱导的，从而提供了一个负反馈回路来终止有丝分裂14，15。在这里，我们报告直接的实验证据表明，细胞周期蛋白的蛋白水解可以触发添加cdc 2激酶的间期Xenopuseggs的无细胞提取物。
THE cell cycles of earlyXenopus embryosconsist of a rapid succession of alternating S and M phases1. These cycles are controlled by the activity of a protein kinase complex (cdc2 kinase) which contains two subunits. One subunit is encoded by the frog homologue of the fission yeastcdc2+gene, p34cdc2(ref. 2) and the other is a cyclin3. The concentration of cyclins follows a sawtooth oscillation because they accumulate in interphase and are destroyed abruptly during mitosis3. The association of cyclin and p34cdc2(refs 4–7) is not sufficient for activation of cdc2 kinase, however; dephosphorylation of key tyrosine and threonine residues of p34cdc2is necessary to turn on its kinase activity8–11. The activity of cdc2 kinase is thus regulated by a combination of translational and post-translational mechanisms. The loss of cdc2 kinase activity at the end of mitosis depends on the destruction of the cyclin subunits3,4,12,13. It has been suggested that this destruction is induced by cdc2 kinase itself, thereby providing a negative feedback loop to terminate mitosis14,15. Here we report direct experimental evidence for this idea by showing that cyclin proteolysis can be triggered by adding cdc2 kinase to a cell-free extract of interphaseXenopuseggs.