From quiescence to proliferation: Cdk oscillations drive the mammalian cell cycle.
From quiescence to proliferation: Cdk oscillations drive the mammalian cell cycle.
复制标题
DOI：
10.3389/fphys.2012.00413
复制
发表时间：
2012
影响因子：
4
通讯作者：
Goldbeter A
中科院分区：
文献类型：
--
作者：
Gérard C;Goldbeter A
我们最近提出了一个详细的模型，描述了驱动哺乳动物细胞周期的细胞周期蛋白依赖性激酶（Cdks）网络的动力学（Gérard和Goldbeter，）。该模型包含四个模块，每个模块围绕一个细胞周期蛋白/Cdk复合物。细胞周期蛋白D/Cdk 4 -6和细胞周期蛋白E/Cdk 2分别促进G1期进展和诱导G1/S转换;细胞周期蛋白A/Cdk 2确保S期进展和S/G2转换，而细胞周期蛋白B/Cdk 1的活性导致G2/M转换。该模型表明，在足够量的生长因子的存在下，Cdk网络能够以持续振荡的形式进行时间自组织，这对应于控制细胞周期的连续阶段的各种细胞周期蛋白/Cdk复合物的有序、顺序激活。结果表明，从细胞静止到细胞增殖的切换对应于Cdk网络中从稳定稳态到持续振荡的转变。这种转变取决于促进或阻碍细胞周期进展的因素之间的微调平衡。我们表明，从静止到增殖的过渡可以以多种方式发生，改变这种平衡。借助于分岔图，我们分析了Cdk网络的振荡机制。最后，我们表明，详细的模型的复杂性可以大大降低，而不会失去其关键的动力学特性，考虑骨架模型的Cdk网络。使用这样一个骨架模型的哺乳动物细胞周期，我们表明，正反馈（PF）回路增强的幅度和稳健性的Cdk振荡相对于分子噪声。我们比较了驱动哺乳动物细胞周期的Cdk网络模型的详细版本和骨架版本的相对优点。
We recently proposed a detailed model describing the dynamics of the network of cyclin-dependent kinases (Cdks) driving the mammalian cell cycle (Gérard and Goldbeter,). The model contains four modules, each centered around one cyclin/Cdk complex. Cyclin D/Cdk4–6 and cyclin E/Cdk2 promote progression in G1 and elicit the G1/S transition, respectively; cyclin A/Cdk2 ensures progression in S and the transition S/G2, while the activity of cyclin B/Cdk1 brings about the G2/M transition. This model shows that in the presence of sufficient amounts of growth factor the Cdk network is capable of temporal self-organization in the form of sustained oscillations, which correspond to the ordered, sequential activation of the various cyclin/Cdk complexes that control the successive phases of the cell cycle. The results suggest that the switch from cellular quiescence to cell proliferation corresponds to the transition from a stable steady state to sustained oscillations in the Cdk network. The transition depends on a finely tuned balance between factors that promote or hinder progression in the cell cycle. We show that the transition from quiescence to proliferation can occur in multiple ways that alter this balance. By resorting to bifurcation diagrams, we analyze the mechanism of oscillations in the Cdk network. Finally, we show that the complexity of the detailed model can be greatly reduced, without losing its key dynamical properties, by considering a skeleton model for the Cdk network. Using such a skeleton model for the mammalian cell cycle we show that positive feedback (PF) loops enhance the amplitude and the robustness of Cdk oscillations with respect to molecular noise. We compare the relative merits of the detailed and skeleton versions of the model for the Cdk network driving the mammalian cell cycle.
登录
查看更多内容
影响因子：
11.2
作者：
Gauger, MA;Sancar, A
通讯作者：
Sancar, A
影响因子：
6
作者：
Bjarnason, GA;Jordan, RCK;Sothern, RB
通讯作者：
Sothern, RB
影响因子：
4.3
作者：
Ciliberto A;Capuani F;Tyson JJ
通讯作者：
Tyson JJ
影响因子：
4.3
作者：
Gérard C;Goldbeter A
通讯作者：
Goldbeter A
影响因子：
11.8
作者：
Buttitta, Laura A.;Katzaroff, Alexia J.;Edgar, Bruce A.
通讯作者：
Edgar, Bruce A.