Lew D J, Reed S I
Department of Molecular Biology, Scripps Research Institute, La Jolla, California 92037.
J Cell Biol. 1993 Mar;120(6):1305-20. doi: 10.1083/jcb.120.6.1305.
Analysis of cell cycle regulation in the budding yeast Saccharomyces cerevisiae has shown that a central regulatory protein kinase, Cdc28, undergoes changes in activity through the cell cycle by associating with distinct groups of cyclins that accumulate at different times. The various cyclin/Cdc28 complexes control different aspects of cell cycle progression, including the commitment step known as START and mitosis. We found that altering the activity of Cdc28 had profound effects on morphogenesis during the yeast cell cycle. Our results suggest that activation of Cdc28 by G1 cyclins (Cln1, Cln2, or Cln3) in unbudded G1 cells triggers polarization of the cortical actin cytoskeleton to a specialized pre-bud site at one end of the cell, while activation of Cdc28 by mitotic cyclins (Clb1 or Clb2) in budded G2 cells causes depolarization of the cortical actin cytoskeleton and secretory apparatus. Inactivation of Cdc28 following cyclin destruction in mitosis triggers redistribution of cortical actin structures to the neck region for cytokinesis. In the case of pre-bud site assembly following START, we found that the actin rearrangement could be triggered by Cln/Cdc28 activation in the absence of de novo protein synthesis, suggesting that the kinase may directly phosphorylate substrates (such as actin-binding proteins) that regulate actin distribution in cells.
对芽殖酵母酿酒酵母细胞周期调控的分析表明，一种核心调控蛋白激酶Cdc28，在细胞周期中通过与在不同时间积累的不同细胞周期蛋白组相结合，其活性发生变化。各种细胞周期蛋白/Cdc28复合物控制细胞周期进程的不同方面，包括称为START的起始步骤和有丝分裂。我们发现，改变Cdc28的活性对酵母细胞周期中的形态发生有深远影响。我们的结果表明，在未出芽的G1细胞中，G1细胞周期蛋白（Cln1、Cln2或Cln3）激活Cdc28会触发皮质肌动蛋白细胞骨架向细胞一端的一个特殊芽前位点极化，而在出芽的G2细胞中，有丝分裂细胞周期蛋白（Clb1或Clb2）激活Cdc28会导致皮质肌动蛋白细胞骨架和分泌装置去极化。有丝分裂中细胞周期蛋白破坏后Cdc28的失活会触发皮质肌动蛋白结构重新分布到颈部区域进行胞质分裂。在START后芽前位点组装的情况下，我们发现肌动蛋白重排可以在没有从头蛋白质合成的情况下由Cln/Cdc28激活触发，这表明该激酶可能直接磷酸化调节细胞中肌动蛋白分布的底物（如肌动蛋白结合蛋白）。
