美国弗朗西斯·克里克研究所Paul Nurse小组的一项最新研究揭示了细胞周期蛋白依赖性激酶对有丝分裂的时空调控。该研究于2025年6月25日发表于国际一流学术期刊《自然》杂志上。

在分裂酵母中，课题组发现CDK首先在核胞中被激活，并且在核胞和细胞质之间的双稳态反应明显不同，核胞中的双稳态反应更强，核胞驱动有丝分裂信号从那里传播到细胞质。取消周期蛋白- cdk在中心体上的定位导致激活仅发生在核仁中，在空间上使核仁和细胞质发生有丝分裂，这表明中心体周期蛋白- cdk起着“信号中继器”的作用。研究组提出关键的有丝分裂调控系统在靠近DNA的核核中运作，这使得DNA的不完全复制和DNA损伤能够被有效地监测，以保持基因组的完整性，并在CDK控制网络中整合倍性。这一时空调控框架建立了控制有丝分裂开始的核心原则，并强调CDK控制系统在核核和细胞质中不同的调控区域内运作。

据了解，有丝分裂的开始是真核细胞增殖的关键阶段。关于有丝分裂控制的普遍观点是，细胞周期蛋白依赖性激酶（CDK）首先在细胞质中被激活，在中心体上启动有丝分裂。CDK激活的双稳定性确保了这种转变是不可逆的，但这种转变如何在空间区隔细胞中展开尚不清楚。

附：英文原文

Title: Spatiotemporal orchestration of mitosis by cyclin-dependent kinase

Author: Kapadia, Nitin, Nurse, Paul

Issue&Volume: 2025-06-25

Abstract: Mitotic onset is a critical transition for eukaryotic cell proliferation. The commonly held view of mitotic control is that the master regulator, cyclin-dependent kinase (CDK), is first activated in the cytoplasm, at the centrosome, initiating mitosis1,2,3. Bistability in CDK activation ensures that the transition is irreversible, but how this unfolds in a spatially compartmentalized cell is unknown4,5,6,7,8. Here, using fission yeast, we show that CDK is first activated in the nucleus, and that the bistable responses differ markedly between the nucleus and the cytoplasm, with a stronger response in the nucleus driving mitotic signal propagation from there to the cytoplasm. Abolishing cyclin–CDK localization to the centrosome led to activation occurring only in the nucleus, spatially uncoupling the nucleus and cytoplasm mitotically, suggesting that centrosomal cyclin–CDK acts as a ‘signal relayer’. We propose that the key mitotic regulatory system operates in the nucleus in proximity to DNA, which enables incomplete DNA replication and DNA damage to be effectively monitored to preserve genome integrity and to integrate ploidy within the CDK control network. This spatiotemporal regulatory framework establishes core principles for control of the onset of mitosis and highlights that the CDK control system operates within distinct regulatory domains in the nucleus and cytoplasm.

DOI: 10.1038/s41586-025-09172-y

Source: https://www.nature.com/articles/s41586-025-09172-y