Systems Biology, School of Biosciences and Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, UK.
Centre for Mathematical and Computational Biology, CMCB, University of Surrey, Guildford, UK.
NPJ Syst Biol Appl. 2020 Apr 3;6(1):8. doi: 10.1038/s41540-020-0125-0.
Some biological networks exhibit oscillations in their components to convert stimuli to time-dependent responses. The eukaryotic cell cycle is such a case, being governed by waves of cyclin-dependent kinase (cyclin/Cdk) activities that rise and fall with specific timing and guarantee its timely occurrence. Disruption of cyclin/Cdk oscillations could result in dysfunction through reduced cell division. Therefore, it is of interest to capture properties of network designs that exhibit robust oscillations. Here we show that a minimal yeast cell cycle network is able to oscillate autonomously, and that cyclin/Cdk-mediated positive feedback loops (PFLs) and Clb3-centered regulations sustain cyclin/Cdk oscillations, in known and hypothetical network designs. We propose that Clb3-mediated coordination of cyclin/Cdk waves reconciles checkpoint and oscillatory cell cycle models. Considering the evolutionary conservation of the cyclin/Cdk network across eukaryotes, we hypothesize that functional ("healthy") phenotypes require the capacity to oscillate autonomously whereas dysfunctional (potentially "diseased") phenotypes may lack this capacity.
一些生物网络的组成部分表现出振荡，以将刺激转换为时间相关的反应。真核细胞周期就是这种情况，它受细胞周期蛋白依赖性激酶（cyclin/Cdk）活性的波动控制，这些活性具有特定的时间和保证其及时发生。cyclin/Cdk 振荡的破坏可能会导致细胞分裂减少而导致功能障碍。因此，捕捉表现出稳健振荡的网络设计的特性是很有意义的。在这里，我们表明，一个最小的酵母细胞周期网络能够自主振荡，并且 cyclin/Cdk 介导的正反馈环（PFL）和以 Clb3 为中心的调节维持 cyclin/Cdk 振荡，在已知和假设的网络设计中也是如此。我们提出，Clb3 介导的 cyclin/Cdk 波的协调调和了检查点和振荡细胞周期模型。考虑到细胞周期蛋白/CDK 网络在真核生物中的进化保守性，我们假设功能（“健康”）表型需要自主振荡的能力，而功能障碍（潜在的“疾病”）表型可能缺乏这种能力。
