Entrainment of the mammalian cell cycle by the circadian clock: modeling two coupled cellular rhythms.
Entrainment of the mammalian cell cycle by the circadian clock: modeling two coupled cellular rhythms.
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DOI：
10.1371/journal.pcbi.1002516
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发表时间：
2012-05
影响因子：
4.3
通讯作者：
Goldbeter A
中科院分区：
文献类型：
--
作者：
Gérard C;Goldbeter A
细胞分裂周期和生物钟代表了两种主要的细胞节律。这两个周期性过程以多种方式耦合，因为细胞周期网络的几个分子组成部分以昼夜节律的方式控制。例如，在控制细胞周期沿着连续阶段进展的细胞周期蛋白依赖性激酶（Cdks）网络中，抑制G2/M转换的激酶Wee 1的合成被在生物钟网络中起中心作用的复合物CLOCK-BMAL 1增强。后一种网络的另一种成分REV-ERB α抑制Cdk抑制剂p21的合成。此外，促进G1细胞周期蛋白合成的癌基因c-Myc的合成被CLOCK-BMAL 1抑制。使用详细的计算模型的两个网络，我们调查的条件下，哺乳动物细胞周期可以夹带的生物钟。我们表明，细胞周期可以带来振荡的周期为24小时或48小时时，其自主周期耦合前是在一个适当的范围内。该模型表明，多种模式的耦合的组合并不一定有利于夹带细胞周期的生物钟。夹带也可能是由于控制进入G1的生长因子水平的昼夜变化而发生。在夹带的范围之外，与昼夜节律钟的耦合可能导致细胞周期和昼夜节律系统中的断开振荡，或者导致细胞周期以内复制、复杂周期振荡或混沌形式的复杂振荡动力学。该模型预测，从夹带到24小时或48小时的过渡可能会发生耦合到生物钟或生长因子的水平低于临界值的强度时。细胞周期和生物钟是两种主要的细胞节律。这两个周期性过程通过多种调节相互作用紧密耦合;细胞周期机制的几个组成部分确实受到昼夜节律网络的控制。通过使用详细的计算模型的细胞周期和昼夜节律网络，我们调查的条件下，哺乳动物细胞周期可以夹带的生物钟。我们表明，夹带到一个昼夜节律周期时，可以发生耦合前的细胞周期小于或大于24小时。也可观察到夹带至48 h。多重耦合模式的存在不会扩大夹带的范围。与生物钟的耦合也可能导致细胞周期的复杂振荡动力学，其形式为内复制、复杂周期振荡或混沌振荡。该模型预测，夹带的细胞周期也可能导致从昼夜变化的生长因子门控进入G1，从夹带期24小时至48小时的过渡可能导致耦合强度或生长因子的水平下降。
The cell division cycle and the circadian clock represent two major cellular rhythms. These two periodic processes are coupled in multiple ways, given that several molecular components of the cell cycle network are controlled in a circadian manner. For example, in the network of cyclin-dependent kinases (Cdks) that governs progression along the successive phases of the cell cycle, the synthesis of the kinase Wee1, which inhibits the G2/M transition, is enhanced by the complex CLOCK-BMAL1 that plays a central role in the circadian clock network. Another component of the latter network, REV-ERBα, inhibits the synthesis of the Cdk inhibitor p21. Moreover, the synthesis of the oncogene c-Myc, which promotes G1 cyclin synthesis, is repressed by CLOCK-BMAL1. Using detailed computational models for the two networks we investigate the conditions in which the mammalian cell cycle can be entrained by the circadian clock. We show that the cell cycle can be brought to oscillate at a period of 24 h or 48 h when its autonomous period prior to coupling is in an appropriate range. The model indicates that the combination of multiple modes of coupling does not necessarily facilitate entrainment of the cell cycle by the circadian clock. Entrainment can also occur as a result of circadian variations in the level of a growth factor controlling entry into G1. Outside the range of entrainment, the coupling to the circadian clock may lead to disconnected oscillations in the cell cycle and the circadian system, or to complex oscillatory dynamics of the cell cycle in the form of endoreplication, complex periodic oscillations or chaos. The model predicts that the transition from entrainment to 24 h or 48 h might occur when the strength of coupling to the circadian clock or the level of growth factor decrease below critical values. The cell cycle and the circadian clock are two major cellular rhythms. These two periodic processes are tightly coupled through multiple regulatory interactions; several components of the cell cycle machinery are indeed controlled by the circadian network. By using detailed computational models for the cell cycle and circadian networks we investigate the conditions in which the mammalian cell cycle can be entrained by the circadian clock. We show that entrainment to a circadian period can occur when the period of the cell cycle prior to coupling is either smaller or larger than 24 h. Entrainment to 48 h can also be observed. The presence of multiple modes of coupling does not enlarge the domain of entrainment. Coupling to the circadian clock may also lead to complex oscillatory dynamics of the cell cycle in the form of endoreplication, complex periodic oscillations, or chaotic oscillations. The model predicts that entrainment of the cell cycle could also result from the circadian variation of a growth factor gating entry into G1, and that the transition from an entrained period of 24 h to 48 h might result from a decrease in coupling strength or in the level of growth factor.
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DOI：
10.4161/cc.9.6.11046
发表时间：
2010-03-15
期刊：
Cell cycle (Georgetown, Tex.)
影响因子：
--
作者：
Gery S;Koeffler HP
通讯作者：
Koeffler HP
影响因子：
11.2
作者：
Gauger, MA;Sancar, A
通讯作者：
Sancar, A
影响因子：
4.3
作者：
Johnson, Carl Hirschie
通讯作者：
Johnson, Carl Hirschie
影响因子：
6
作者：
Bjarnason, GA;Jordan, RCK;Sothern, RB
通讯作者：
Sothern, RB
DOI：
10.1073/pnas.0709879104
发表时间：
2007-12-11
影响因子：
11.1
作者：
Forester, Craig M.;Maddox, Jessica;Virshup, David M.
通讯作者：
Virshup, David M.