IEEE Trans Nanobioscience. 2020 Jan;19(1):35-47. doi: 10.1109/TNB.2019.2946336. Epub 2019 Oct 8.
Oscillation expression of NF- [Formula: see text] signaling system can lead to nuclear NF- [Formula: see text] accumulation which involving various important cellular processes including immune response, inflammation and cancer development. Negative feedback circuits involved in NF- [Formula: see text] signaling system are generally believed to be responsible for the oscillation expression. In view of feedback loops involving time delays resulting from transcription, transcript splicing and processing, and protein synthesis, in this paper, a mathematical model with time delay to describe the core negative feedback circuits centered on NF- [Formula: see text] including [Formula: see text] and A20 -like proteins is developed. Here, the time delay refer to the time demand of transcription and translation process of [Formula: see text]. First, the results suggest that time delay can drive oscillation dynamics of NF- [Formula: see text] signaling system. Concretely, there exists a critical value of time delay. When the time delay exceeds the critical value, the system exhibits oscillation dynamics, and with the increase of time delay, the amplitude and period increase accordingly. Second, analysis indicate that A20 -like proteins are able to change the amplitude and period of the nuclear NF- [Formula: see text] oscillations. In addition, the effects of several important parameters on the nuclear NF- [Formula: see text] oscillations are also discussed. Finally, a prediction is formed, which is shortening time delay, repairing and maintaining the function of A20 -like proteins, and increasing [Formula: see text] transcription rate may be new clues to related disease treatment.
NF-κB 信号系统的振荡表达可导致核 NF-κB 积累,涉及包括免疫反应、炎症和癌症发展在内的各种重要细胞过程。NF-κB 信号系统中的负反馈回路通常被认为是导致振荡表达的原因。鉴于转录、转录剪接和加工以及蛋白质合成过程中涉及的时间延迟反馈回路,本文提出了一个带有时间延迟的数学模型,用于描述以 NF-κB 为中心的核心负反馈回路,包括 IκB 和 A20 样蛋白。这里的时间延迟是指 NF-κB 信号转导过程中转录和翻译所需的时间。首先,结果表明时间延迟可以驱动 NF-κB 信号系统的振荡动力学。具体来说,存在一个临界时间延迟值。当时间延迟超过临界值时,系统表现出振荡动力学,并且随着时间延迟的增加,幅度和周期相应增加。其次,分析表明 A20 样蛋白能够改变核 NF-κB 振荡的幅度和周期。此外,还讨论了几个重要参数对核 NF-κB 振荡的影响。最后,形成了一个预测,即缩短时间延迟、修复和维持 A20 样蛋白的功能、增加 IκB 转录率可能是相关疾病治疗的新线索。