Cell Division and Cancer Group, Spanish National Cancer Research Centre, Madrid, Spain.
Physiol Rev. 2011 Jul;91(3):973-1007. doi: 10.1152/physrev.00025.2010.
The basic biology of the cell division cycle and its control by protein kinases was originally studied through genetic and biochemical studies in yeast and other model organisms. The major regulatory mechanisms identified in this pioneer work are conserved in mammals. However, recent studies in different cell types or genetic models are now providing a new perspective on the function of these major cell cycle regulators in different tissues. Here, we review the physiological relevance of mammalian cell cycle kinases such as cyclin-dependent kinases (Cdks), Aurora and Polo-like kinases, and mitotic checkpoint regulators (Bub1, BubR1, and Mps1) as well as other less-studied enzymes such as Cdc7, Nek proteins, or Mastl and their implications in development, tissue homeostasis, and human disease. Among these functions, the control of self-renewal or asymmetric cell division in stem/progenitor cells and the ability to regenerate injured tissues is a central issue in current research. In addition, many of these proteins play previously unexpected roles in metabolism, cardiovascular function, or neuron biology. The modulation of their enzymatic activity may therefore have multiple therapeutic benefits in human disease.
细胞分裂周期的基本生物学及其被蛋白激酶的调控最初是通过酵母和其他模式生物的遗传和生化研究来研究的。在这项开创性工作中确定的主要调控机制在哺乳动物中是保守的。然而，目前不同细胞类型或遗传模型的研究正在为这些主要细胞周期调节剂在不同组织中的功能提供新的视角。在这里，我们回顾了哺乳动物细胞周期激酶（如细胞周期蛋白依赖性激酶（Cdks）、极光和 Polo 样激酶）和有丝分裂检查点调节剂（Bub1、BubR1 和 Mps1）以及其他研究较少的酶（如 Cdc7、Nek 蛋白或 Mastl）的生理相关性，以及它们在发育、组织稳态和人类疾病中的作用。在这些功能中，控制干细胞/祖细胞的自我更新或不对称细胞分裂以及修复受损组织的能力是当前研究的核心问题。此外，这些蛋白质中的许多在代谢、心血管功能或神经元生物学中发挥着以前意想不到的作用。因此，调节它们的酶活性可能在人类疾病中具有多种治疗益处。
