Tatum Natalie J, Endicott Jane A
Cancer Research UK Newcastle Drug Discovery Unit, Newcastle Centre for Cancer, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne NE2 4HH, United Kingdom.
Cancer Research UK Newcastle Drug Discovery Unit, Newcastle Centre for Cancer, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne NE2 4HH, United Kingdom.
Semin Cell Dev Biol. 2020 Nov;107:4-20. doi: 10.1016/j.semcdb.2020.04.021. Epub 2020 May 13.
Proteins of the cyclin family have divergent sequences and execute diverse roles within the cell while sharing a common fold: the cyclin box domain. Structural studies of cyclins have played a key role in our characterization and understanding of cellular processes that they control, though to date only ten of the 29 CDK-activating cyclins have been structurally characterized by X-ray crystallography or cryo-electron microscopy with or without their cognate kinases. In this review, we survey the available structures of human cyclins, highlighting their molecular features in the context of their cellular roles. We pay particular attention to how cyclin activity is regulated through fine control of degradation motif recognition and ubiquitination. Finally, we discuss the emergent roles of cyclins independent of their roles as cyclin-dependent protein kinase activators, demonstrating the cyclin box domain to be a versatile and generalized scaffolding domain for protein-protein interactions across the cellular machinery.
细胞周期蛋白家族的蛋白质序列各异，虽共享一个共同的折叠结构域——细胞周期蛋白盒结构域，但在细胞内发挥着不同的作用。细胞周期蛋白的结构研究在我们对其控制的细胞过程的表征和理解中发挥了关键作用，不过迄今为止，29种细胞周期蛋白依赖性激酶（CDK）激活型细胞周期蛋白中，只有10种通过X射线晶体学或冷冻电子显微镜进行了结构表征，无论有无其同源激酶。在这篇综述中，我们概述了人类细胞周期蛋白的现有结构，突出了它们在细胞功能背景下的分子特征。我们特别关注细胞周期蛋白活性如何通过对降解基序识别和泛素化的精细控制来调节。最后，我们讨论了细胞周期蛋白独立于其作为细胞周期蛋白依赖性蛋白激酶激活剂的作用所呈现的新作用，证明细胞周期蛋白盒结构域是整个细胞机制中蛋白质 - 蛋白质相互作用的通用且广泛的支架结构域。
