Center for Human Genetic Research, Massachusetts General Hospital, Harvard Medical School, Richard B. Simches Research Center, 185 Cambridge Street, Boston, MA, 02114, USA,
Cell Mol Life Sci. 2014 Feb;71(4):629-39. doi: 10.1007/s00018-013-1449-3. Epub 2013 Aug 22.
Cyclin-dependent kinases (Cdk) are a family of serine/threonine protein kinases that regulate eukaryotic cell cycle progression. Their ability to modulate the cell cycle has made them an attractive target for anti-cancer therapies. Cdk protein function has been studied in a variety of Eukaryotes ranging from yeast to humans. In the social amoebozoan Dictyostelium discoideum, several homologues of mammalian Cdks have been identified and characterized. The life cycle of this model organism is comprised of a feeding stage where single cells grow and divide mitotically as they feed on their bacterial food source and a multicellular developmental stage that is induced by starvation. Thus it is a valuable system for studying a variety of cellular and developmental processes. In this review I summarize the current knowledge of the Cdk protein family in Dictyostelium by highlighting the research efforts focused on the characterization of Cdk1, Cdk5, and Cdk8 in this model Eukaryote. Accumulated evidence indicates that each protein performs distinct functions during the Dictyostelium life cycle with Cdk1 being required for growth and Cdk5 and Cdk8 being required for processes that occur during development. Recent studies have shown that Dictyostelium Cdk5 shares attributes with mammalian Cdk5 and that the mammalian Cdk inhibitor roscovitine can be used to inhibit Cdk5 activity in Dictyostelium. Together, these results show that Dictyostelium can be used as a model system for studying Cdk protein function.
细胞周期蛋白依赖性激酶(Cdk)是一组丝氨酸/苏氨酸蛋白激酶,可调节真核细胞周期进程。它们调节细胞周期的能力使其成为抗癌治疗的有吸引力的靶点。已经在从酵母到人类的各种真核生物中研究了 Cdk 蛋白的功能。在黏菌 Dictyostelium discoideum 中,已经鉴定并表征了几种哺乳动物 Cdk 的同源物。该模式生物的生命周期包括一个摄取阶段,在此阶段,单细胞在以细菌为食源的情况下通过有丝分裂生长和分裂;以及一个由饥饿诱导的多细胞发育阶段。因此,它是研究各种细胞和发育过程的有价值的系统。在这篇综述中,我通过强调集中在这个模式真核生物中 Cdk1、Cdk5 和 Cdk8 表征的研究工作,总结了 Cdk 蛋白家族在 Dictyostelium 中的现有知识。积累的证据表明,每种蛋白质在 Dictyostelium 的生命周期中都具有不同的功能,Cdk1 是生长所必需的,Cdk5 和 Cdk8 是发育过程中所必需的。最近的研究表明,黏菌 Cdk5 具有与哺乳动物 Cdk5 相似的特性,并且哺乳动物 Cdk 抑制剂 roscovitine 可用于抑制黏菌中的 Cdk5 活性。这些结果表明,黏菌可以用作研究 Cdk 蛋白功能的模型系统。