Two redundant oscillatory mechanisms in the yeast cell cycle
Two redundant oscillatory mechanisms in the yeast cell cycle
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DOI：
10.1016/s1534-5807(03)00119-9
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发表时间：
2003-05-01
影响因子：
11.8
通讯作者：
Cross, FR
中科院分区：
文献类型：
--
作者：
Cross, FR
细胞分裂周期需要B型细胞周期蛋白（Clb）-Cdk 1激酶活性的振荡。振荡是由于周期性的细胞周期蛋白降解后期促进复合物（APC）激活Cdc 20或Cdh 1，并周期性积累的Sic 1抑制剂。这里提出的结果表明，控制Clb激酶水平的调节机制嵌入两个不同的振荡机制。一种是“弛张振荡器”，涉及两种亚稳态之间的交替：Clb高/抑制剂（Sic 1/APC-Cdh 1）低，Clb低/抑制剂高。另一个是“负反馈振荡器”，涉及APC-Cdc 20的Clb激酶激活，导致Clb降解。遗传学分析表明，这两种机制可以独立发挥作用，并且需要两种机制的失活来防止有丝分裂。计算建模证实，两个这样的机制可以连接到产生一个强大的细胞周期控制系统。
The cell division cycle requires oscillations in activity of B-type cyclin (Clb)-Cdk1 kinases. Oscillations are due to periodic cyclin degradation by the anaphase-promoting complex (APC) activated by Cdc20 or Cdh1, and to cyclical accumulation of the Sic1 inhibitor. The results presented here suggest that the regulatory machinery controlling Clb kinase levels embeds two distinct oscillatory mechanisms. One, a "relaxation oscillator," involves alternation between two meta-stable states: Clb high/inhibitors (Sic1/APC-Cdh1) low, and Clb low/inhibitors high. The other, a "negative feedback oscillator," involves Clb kinase activation of APC-Cdc20, leading to Clb degradation. Genetic analysis suggests that these two mechanisms can function independently, and inactivation of both mechanisms is required to prevent mitosis. Computational modeling confirms that two such mechanisms can be linked to yield a robust cell cycle control system.