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首页> 外文期刊>Nature cell biology >The Cdk1-APC/C cell cycle oscillator circuit functions as a time-delayed, ultrasensitive switch
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The Cdk1-APC/C cell cycle oscillator circuit functions as a time-delayed, ultrasensitive switch

机译:Cdk1-APC / C细胞周期振荡器电路用作延时超灵敏开关

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Despite the complexity and variety of biological oscillators, their core design invariably includes an essential negative feedback loop. In the Xenopus laevis embryonic cell cycle oscillator, this loop consists of the kinase cyclin B-Cdk1 and the ubiquitin ligase APC/C Cdc20; active Cdk1 activates APC/C Cdc20, which then brings about cyclin B degradation and inactivates Cdk1. Here we ask how this negative feedback loop functions quantitatively, with the aim of understanding what mechanisms keep the Cdk1-APC/C Cdc20 system from settling into a stable steady state with intermediate levels of Cdk1 and APC/C Cdc20 activity. We found that the system operates as a time-delayed, digital switch, with a time lag of ~ 15 min between Cdk1 and APC/C Cdc20 activation and a tremendously high degree of ultrasensitivity (n H ≈17). Computational modelling shows how these attributes contribute to the generation of robust, clock-like oscillations. Principles uncovered here may also apply to other activator-repressor oscillators and help in designing robust synthetic clocks.
机译:尽管生物振荡器复杂且种类繁多,但它们的核心设计始终包括必不可少的负反馈环路。在非洲爪蟾胚胎细胞周期振荡器中,该环由激酶细胞周期蛋白B-Cdk1和泛素连接酶APC / C Cdc20组成。活性Cdk1激活APC / C Cdc20,然后导致细胞周期蛋白B降解并使Cdk1失活。在这里,我们问这个负反馈回路如何定量地起作用,目的是了解哪些机制使Cdk1-APC / C Cdc20系统无法稳定进入具有Cdk1和APC / C Cdc20活性中间水平的稳定稳态。我们发现该系统是一个延时的数字开关,在Cdk1和APC / C Cdc20激活之间存在约15分钟的时滞,并且具有极高的超灵敏性(n H≈17)。计算建模显示了这些属性如何促进鲁棒的,类似时钟的振荡的产生。此处揭示的原理也可能适用于其他激活-抑制振荡器,并有助于设计可靠的合成时钟。

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