Oredsson S M
Department of Cell and Organism Biology, Lund University, S-223 62 Lund, Sweden.
Biochem Soc Trans. 2003 Apr;31(2):366-70. doi: 10.1042/bst0310366.
The driving force of the cell cycle is the activities of cyclin-dependent kinases (CDKs). Key steps in the regulation of the cell cycle therefore must impinge upon the activities of the CDKs. CDKs exert their functions when bound to cyclins that are expressed cyclically during the cell cycle. Polyamine biosynthesis varies bicyclically during the cell cycle with peaks in enzyme activities at the G(1)/S and S/G(2) transitions. The enzyme activities are regulated at transcriptional, translational and post-translational levels. When cells are seeded in the presence of drugs that interfere with polyamine biosynthesis, cell cycle progression is affected within one cell cycle after seeding. The cell cycle phase that is most sensitive to polyamine biosynthesis inhibition is the S phase, while effects on the G(1) and G(2)/M phases occur at later time points. The elongation step of DNA replication is negatively affected when polyamine pools are not allowed to increase normally during cell proliferation. Cyclin A is expressed during the S phase and cyclin A/CDK2 is important for a normal rate of DNA elongation. Cyclin A expression is lowered in cells treated with polyamine biosynthesis inhibitors. Thus, polyamines may affect S phase progression by participating in the regulation of cyclin A expression.
细胞周期的驱动力是细胞周期蛋白依赖性激酶（CDK）的活性。因此，细胞周期调控中的关键步骤必定会影响CDK的活性。CDK只有在与细胞周期蛋白结合时才能发挥其功能，而细胞周期蛋白在细胞周期中呈周期性表达。多胺生物合成在细胞周期中呈双循环变化，在G(1)/S期和S/G(2)期转换时酶活性达到峰值。酶活性在转录、翻译和翻译后水平受到调控。当细胞在存在干扰多胺生物合成的药物的情况下接种时，接种后一个细胞周期内细胞周期进程就会受到影响。对多胺生物合成抑制最敏感的细胞周期阶段是S期，而对G(1)期和G(2)/M期的影响则在较晚时间点出现。当细胞增殖过程中多胺池不能正常增加时，DNA复制的延伸步骤会受到负面影响。细胞周期蛋白A在S期表达，细胞周期蛋白A/CDK2对DNA正常延伸速率很重要。在用多胺生物合成抑制剂处理的细胞中，细胞周期蛋白A的表达会降低。因此，多胺可能通过参与细胞周期蛋白A表达的调控来影响S期进程。
