Contribution of time delays to p53 oscillation in DNA damage response
Contribution of time delays to p53 oscillation in DNA damage response
复制标题
时间延迟对 DNA 损伤反应中 p53 振荡的贡献
DOI：
10.1049/iet-syb.2019.0006
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发表时间：
2019
影响因子：
2.3
通讯作者：
Jin Zhou
中科院分区：
文献类型：
--
作者：
Conghua Wang;Haihong Liu;Jin Zhou
虽然P53基因网络的振荡动力学已经得到了广泛的研究，但对延迟诱导的振荡机制的了解仍然有限。本文研究了含有两个延迟负反馈环的P53基因网络的综合数学模型。结果表明，MDM2蛋白合成时滞可以很好地控制脉冲形状，但不能单独引起P53振荡，而Wip1蛋白合成所需的时滞诱导Hopf分叉驱动P53振荡。此外，这两个延迟的协同作用会导致P53基因网络提前振荡，表明P53在受损细胞中更早开始修复过程。此外，还讨论了模型的稳定性和分叉，这可能突出时滞在P53振荡中的作用。
Although the oscillatory dynamics of the p53 network have been extensively studied, the understanding of the mechanism of delay‐induced oscillations is still limited. In this paper, a comprehensive mathematical model of p53 network is studied, which contains two delayed negative feedback loops. By studying the model with and without explicit delays, the results indicate that the time delay of Mdm2 protein synthesis can well control the pulse shape but cannot induce p53 oscillation alone, while the time delay required for Wip1 protein synthesis induces a Hopf bifurcation to drive p53 oscillation. In addition, the synergy of the two delays will cause the p53 network to oscillate in advance, indicating that p53 begins the repair process earlier in the damaged cell. Furthermore, the stability and bifurcation of the model are addressed, which may highlight the role of time delay in p53 oscillations.