背景回顾：Reactive oxygen species (ROS) at the right concentration promote cell proliferation in cell culture, stem cells, and model organisms. 

提出问题：However, the mystery of how ROS signaling is coordinated with cell cycle progression and integrated into the cell cycle control machinery on the molecular level remains unsolved. 

主要发现：Here, we report increasing levels of mitochondrial ROS during the cell cycle in human cell lines that target cyclin-dependent kinase 2 (CDK2). 

结果1-ROS含量降低、CDK2活性降低：Chemical and metabolic interferences with ROS production decrease T-loop phosphorylation on CDK2 and so impede its full activation and thus its efficient DNA replication. 

结果2-ROS促进CDK磷酸化：ROS regulate CDK2 activity through the oxidation of a conserved cysteine residue near the T-loop, which prevents the binding of the T-loop phosphatase KAP. 

结论：Together, our data reveal how mitochondrial metabolism is coupled with DNA replication and cell cycle progression via ROS, thereby demonstrating how KAP activity toward CDKs can be cell cycle regulated.

 摘 要 

在细胞培养、干细胞以及模式生物中，适当浓度的活性氧能够促进细胞的增殖。但是，ROS信号转导如何与细胞周期过程关联，以及如何作用于细胞周期调控的分子机制还不清楚。本文中，作者发现在人类细胞系中，线粒体ROS含量的增加能够靶向细胞周期依赖性激酶CDK2。通过化学方法或者代谢扰乱ROS的产生，能够降低CDK2的T-loop磷酸化，因此阻碍了CDK2蛋白的完全激活，从而妨碍了高效DNA复制。ROS能够通过氧化T-loop附近的一个保守的半胱氨酸残基，促进T-loop磷酸酶KAP的结合，从而调控CDK2的活性。综上，本文的研究结果揭示了线粒体代谢通过ROS来调控KAP介导的CDK蛋白激活，从而与DNA复制和细胞周期进程相关联。

 Joanne Chory