Combinatorial dynamics of protein synthesis time delay and negative feedback loop in NF-κ B signalling pathway

IF 16.4 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Fang Yan, Li Liu, Qingyun Wang
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引用次数: 1

Abstract

The transcription factor NF-κ B links immune response and inflammatory reaction and its different oscillation patterns determine different cell fates. In this study, a mathematical model with Iκ Bα protein synthesis time delay is developed based on the experimental evidences. The results show that time delay has the ability to drive oscillation of NF-κ B via Hopf bifurcation. Meanwhile, the amplitude and period are sensitive to the time delay. Moreover, the time delay threshold is a function of four parameters characterising the negative feedback loop. Likewise, the parameters also have effects on the amplitude and period of NF-κ B oscillation induced by time delay. Therefore, the oscillation patterns of NF-κ B are collaborative results of time delay coupled with the negative feedback loop. These results not only enhance the understanding of NF-κ B biological oscillation but also provide clues for the development of anti-inflammatory or anti-cancer drugs.

Abstract Image

NF-κ B信号通路中蛋白质合成时滞和负反馈回路的组合动力学
转录因子NF-κ B连接免疫反应和炎症反应,其不同的振荡模式决定不同的细胞命运。本研究基于实验证据,建立了Iκ Bα蛋白合成时滞的数学模型。结果表明,时间延迟能够通过Hopf分岔驱动NF-κ B振荡。同时,振幅和周期对时延敏感。此外,时间延迟阈值是表征负反馈回路的四个参数的函数。同样,这些参数也对延时引起的NF-κ B振荡的幅度和周期有影响。因此,NF-κ B的振荡模式是时间延迟与负反馈环耦合的协同结果。这些结果不仅增强了对NF-κ B生物振荡的认识,而且为抗炎或抗癌药物的开发提供了线索。
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来源期刊
Accounts of Chemical Research
Accounts of Chemical Research 化学-化学综合
CiteScore
31.40
自引率
1.10%
发文量
312
审稿时长
2 months
期刊介绍: Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.
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