Section for Biochemistry and Molecular Biology, Faculty of Mathematics and Natural Sciences, University of Oslo, 0316 Oslo, Norway.
Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, 0379 Oslo, Norway.
Int J Mol Sci. 2022 Jan 24;23(3):1293. doi: 10.3390/ijms23031293.
The cyclin-dependent kinase Cdk1 is best known for its function as master regulator of the cell cycle. It phosphorylates several key proteins to control progression through the different phases of the cell cycle. However, studies conducted several decades ago with mammalian cells revealed that Cdk1 also directly regulates the basal transcription machinery, most notably RNA polymerase II. More recent studies in the budding yeast have revisited this function of Cdk1 and also revealed that Cdk1 directly controls RNA polymerase III activity. These studies have also provided novel insight into the physiological relevance of this process. For instance, cell cycle-stage-dependent activity of these complexes may be important for meeting the increased demand for various proteins involved in housekeeping, metabolism, and protein synthesis. Recent work also indicates that direct regulation of the RNA polymerase II machinery promotes cell cycle entry. Here, we provide an overview of the regulation of basal transcription by Cdk1, and we hypothesize that the original function of the primordial cell-cycle CDK was to regulate RNAPII and that it later evolved into specialized kinases that govern various aspects of the transcription machinery and the cell cycle.
周期蛋白依赖性激酶 Cdk1 最为人所知的是其作为细胞周期主调控因子的功能。它磷酸化几个关键蛋白来控制细胞周期的不同阶段的进程。然而,几十年前在哺乳动物细胞中进行的研究表明,Cdk1 还直接调节基础转录机制,特别是 RNA 聚合酶 II。在芽殖酵母中的最近研究重新审视了 Cdk1 的这一功能,还揭示了 Cdk1 直接控制 RNA 聚合酶 III 的活性。这些研究还为这一过程的生理相关性提供了新的见解。例如,这些复合物的细胞周期阶段依赖性活性对于满足参与维持生命、代谢和蛋白质合成的各种蛋白质的增加需求可能很重要。最近的工作还表明,对 RNA 聚合酶 II 机制的直接调控促进了细胞周期进入。在这里,我们提供了 Cdk1 对基础转录调控的概述,我们假设原始细胞周期 CDK 的最初功能是调节 RNAPII,后来它进化成专门的激酶,调节转录机制和细胞周期的各个方面。