Timing of events in mitosis
Timing of events in mitosis
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DOI：
10.1016/s0960-9822(01)00662-5
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发表时间：
2002-01-22
期刊：
影响因子：
9.2
通讯作者：
Kirschner, MW
中科院分区：
文献类型：
--
作者：
Georgi, AB;Stukenberg, PT;Kirschner, MW
背景：人们对细胞周期主要转变（例如 G1/S、G2/M 和中期到后期）的调控越来越了解。然而，我们对细胞周期每个阶段（例如 S 期或早期有丝分裂）内事件发生的时间了解甚少。两种极端的监管模式是可能的。 “调节器控制模型”，其中事件的顺序由一系列细胞质调节器的激活控制，例如激酶、磷酸酶或蛋白酶；或“底物控制模型”，其中时间调节是由细胞机器对一组常见激活剂的差异反应决定的。结果：我们试图通过检查有丝分裂期间非洲爪蟾卵提取物中生化和形态事件的时间来区分这两种模型。几种蛋白质对 Cdc2 的激活有不同的延迟反应。我们发现，当这些蛋白质暴露于处于有丝分裂不同时期的提取物时，磷酸化的时间基本上没有改变。同样，当非洲爪蟾间期细胞核在 G2/M 转变后的不同时间添加到提取物中时，它们会以正确的顺序和非常相似的动力学经历所有预期的形态变化。结论：我们的结果表明，在早期有丝分裂（从前期到中期）期间，生化事件（例如磷酸化）和形态事件（例如细胞核中的结构变化）的时间至少部分由底物本身对一组常见信号的响应控制。
Background: Regulation of the major transitions in the cell cycle, such as G1/S, G2/M, and metaphase to anaphase, are increasingly well understood. However, we have a poor understanding of the timing of events within each phase of the cell cycle, such as S phase or early mitosis. Two extreme models of regulation are possible. A "regulator-controlled model" in which the order of events is governed by the activation of a series of cytoplasmic regulators, such as kinases, phosphatases, or proteases; or a "substrate-controlled model" in which temporal regulation is determined by the differential responses of the cellular machinery to a common set of activators.Results: We have tried to distinguish between these two models by examining the timing of both biochemical and morphological events in Xenopus egg extracts during mitosis. Several proteins respond with different delays to the activation of Cdc2. We have found that the timing of phosphorylation is largely unchanged when these proteins are exposed to extracts that have been in mitosis for various periods of time. Similarly, when Xenopus interphase nuclei are added to extracts at different times after the G2/M transition, they undergo all the expected morphological changes in the proper sequence and with very similar kinetics.Conclusions: Our results suggest that during early mitosis (from prophase to metaphase) the timing of biochemical events (such as phosphorylation) and morphological events (such as structural changes in the nucleus) is at least partly controlled by the responses of the substrates themselves to a common set of signals.