Bae Hyeonjeong, Go Young-Hyun, Kwon Taejin, Sung Bong June, Cha Hyuk-Jin
Department of Chemistry, Sogang University, 35 Baekbeom-ro, Mapo-gu, Seoul, 04107, South Korea.
Department of Life Science, Sogang University, 35 Baekbeom-ro, Mapo-gu, Seoul, 04107, South Korea.
Pharm Res. 2019 Feb 22;36(4):57. doi: 10.1007/s11095-019-2570-2.
Since the molecular mechanism of the cell cycle was established, various theoretical models of this process have been developed. A recent study revealed significant variability in cell cycle duration between mother and daughter cells, but this observation has not been incorporated into the theoretical models.
We used fluorescent ubiquitination-based cell cycle indicator (FUCCI) systems and live-monitored the heterogeneity of cell cycle progression within daughter cells, which accounts for dephasing synchrony. To incorporate the variable cell cycle durations into a model, we modified a two-ordinary differential equation (ODE) model based on reciprocal activation between CDK1 and APC.
Our model reproduced the experimental population profile, in which cell cycle synchrony dephased due to variability. Based on this model, we determined parameters for CDK1 and APC in the cell cycle profile after treatment with antimitotic drugs and associated the parameters with the drugs' mode of action as cell cycle inhibitors.
This suggests that this model is useful for determining the mode of action of unknown small molecules on the cell cycle.
自从细胞周期的分子机制确立以来，已经开发了该过程的各种理论模型。最近的一项研究揭示了母细胞和子细胞之间细胞周期持续时间的显著差异，但这一观察结果尚未纳入理论模型。
我们使用基于荧光泛素化的细胞周期指示剂（FUCCI）系统，并实时监测子细胞内细胞周期进程的异质性，这解释了同步相位的消失。为了将可变的细胞周期持续时间纳入模型，我们基于CDK1和APC之间的相互激活修改了一个二阶常微分方程（ODE）模型。
我们的模型再现了实验群体概况，其中细胞周期同步性由于变异性而出现相位偏移。基于该模型，我们确定了抗有丝分裂药物处理后细胞周期概况中CDK1和APC的参数，并将这些参数与药物作为细胞周期抑制剂的作用模式相关联。
这表明该模型对于确定未知小分子对细胞周期的作用模式是有用的。
