Quantitative characterization of a mitotic cyclin threshold regulating exit from mitosis
Quantitative characterization of a mitotic cyclin threshold regulating exit from mitosis
复制标题
DOI：
10.1091/mbc.e04-10-0897
复制
发表时间：
2005-05-01
影响因子：
3.3
通讯作者：
Chen, KC
中科院分区：
文献类型：
--
作者：
Cross, FR;Schroeder, L;Chen, KC
细胞周期蛋白丰度的调控是真核细胞周期调控的核心。已知有丝分裂周期蛋白的强烈过表达将系统锁定在有丝分裂中，但随着这一阈值的接近，控制系统的定量行为仅在非洲爪哇体外提取系统中得到表征。在这里，我们量化了由有丝分裂周期蛋白Clb2的结构性过表达引起的芽期酵母有丝分裂障碍的阈值。在这个阈值附近，系统表现出明显的稳健性丧失，因为这种丢失甚至杂合性对一些调节因子来说是有害的或致命的，即使在正常的周期蛋白表达水平下完全失去这些调节因子也是可以容忍的。最近，我们提出了芽期酵母细胞周期的定量动力学模型。在这里，我们使用这个模型来生成Clb2水平的生化预测，随着Clb2过度表达阈值的接近，异步的以及通过细胞周期进行的。即使在模型生成期间没有这种类型的数据可用，模型预测也可以与生化数据相比较。该模型还预测了Clb2过表达系统的稳健性损失。这些结果有力地证实了模型的预测能力。
Regulation of cyclin abundance is central to eukaryotic cell cycle control. Strong overexpression of mitotic cyclins is known to lock the system in mitosis, but the quantitative behavior of the control system as this threshold is approached has only been characterized in the in vitro Xenopus extract system. Here, we quantitate the threshold for mitotic block in budding yeast caused by constitutive overexpression of the mitotic cyclin Clb2. Near this threshold, the system displays marked loss of robustness, in that loss or even heterozygosity for some regulators becomes deleterious or lethal, even though complete loss of these regulators is tolerated at normal cyclin expression levels. Recently, we presented a quantitative kinetic model of the budding yeast cell cycle. Here, we use this model to generate biochemical predictions for Clb2 levels, asynchronous as well as through the cell cycle, as the Clb2 overexpression threshold is approached. The model predictions compare well with biochemical data, even though no data of-this type were available during model generation. The loss of robustness of the Clb2 overexpressing system is also predicted by the model. These results provide strong confirmation of the model's predictive ability.