Mathematical model of the morphogenesis checkpoint in budding yeast.

Mathematical model of the morphogenesis checkpoint in budding yeast.
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DOI:
10.1083/jcb.200306139
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发表时间:
2003-12-22
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Tyson JJ
Tyson JJ
中科院分区:
其他
文献类型:
--
作者:
Ciliberto A;Novak B;Tyson JJ

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发芽酵母中的形态发生检查点在细胞周期中延迟进展,以响应阻止芽形成的刺激。检查点机制的中心是Swe1激酶:正常情况下,它的激活不活跃,会阻止G2中的细胞周期进程。我们基于对发芽酵母的观察和分裂酵母中类似的控制信号,提出了一个控制Swe1的分子网络。将所提出的Swe1网络与细胞周期蛋白依赖的激酶调控模型合并,转化为一组微分方程组,并进行了数值模拟研究。这些模拟准确地再现了十几个检查点突变的表型。在其他预测中,该模型将一个新的角色归因于Hsl1,一种已知在Swe1降解中发挥作用的激酶:Hsl1也必须间接地对Swe1活性的有效抑制负责。该模型支持这样的观点,即形态发生检查点像其他检查点一样,提高了细胞从细胞周期的一个阶段进入下一个阶段的细胞大小阈值。
The morphogenesis checkpoint in budding yeast delays progression through the cell cycle in response to stimuli that prevent bud formation. Central to the checkpoint mechanism is Swe1 kinase: normally inactive, its activation halts cell cycle progression in G2. We propose a molecular network for Swe1 control, based on published observations of budding yeast and analogous control signals in fission yeast. The proposed Swe1 network is merged with a model of cyclin-dependent kinase regulation, converted into a set of differential equations and studied by numerical simulation. The simulations accurately reproduce the phenotypes of a dozen checkpoint mutants. Among other predictions, the model attributes a new role to Hsl1, a kinase known to play a role in Swe1 degradation: Hsl1 must also be indirectly responsible for potent inhibition of Swe1 activity. The model supports the idea that the morphogenesis checkpoint, like other checkpoints, raises the cell size threshold for progression from one phase of the cell cycle to the next.
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