振荡(细胞信号)
霍普夫分叉
非正面反馈
控制理论(社会学)
反馈回路
共济失调毛细血管扩张
正面反馈
物理
生物系统
计算机科学
拓扑(电路)
分叉
生物
DNA损伤
数学
工程类
DNA
遗传学
人工智能
非线性系统
电压
电气工程
组合数学
控制(管理)
量子力学
计算机安全
作者
Conghua Wang,Haihong Liu,Jin Zhou
出处
期刊:IEEE Transactions on Nanobioscience
[Institute of Electrical and Electronics Engineers]
日期:2019-10-01
卷期号:18 (4): 611-621
被引量:9
标识
DOI:10.1109/tnb.2019.2924079
摘要
DNA damage caused by γ -irradiation initiates oscillatory expression of the p53 genetic network. Although many studies revealed the effects of the p53-Mdm2 circuit on p53 dynamics, a few studies explored the contribution of upstream kinases to p53 oscillation. In this paper, an integrated mathematical model of the p53 network in response to γ -irradiation is studied, which consists of five basic components, two ubiquitous time delays, and two negative feedback loops. It is found that recurrent p53 pulses are externally initiated by ataxia telangiectasia mutated (ATM), and the negative feedback loop formed between ATM and p53, via Wip1, plays a dominant role in generating p53 oscillation. In addition, p53 oscillation requires not only an appropriate Mdm2 negative strength but also a threshold level of Wip1 negative strength. Furthermore, the time delays required for transcription and translation of Mdm2 and Wip1 proteins are essential for p53 oscillation. In particular, the critical value of time delay for inducing oscillation and the properties of delay-driven Hopf bifurcation are theoretically analyzed. As expected, the results are clearly in consistence with biological experiments and observations.
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