具有时滞的P53调控网络的动力学分析

Dynamics Analysis of P53Regulatory Network with Time Delay

肿瘤抑制蛋白P53的动力学在细胞受到压力后对细胞命运起到重要作用。P53动力学与DNA损伤强度和P53信号通路中蛋白质表达水平密切相关。最近的研究考虑了蛋白质PDCD5调控P53信号通路并分析了对P53动力学的影响,却忽略了通路中基因转录和mRNA翻译时滞的作用。在本文,针对PDCD5调控具有时滞的P53信号通路模型,分别考虑有无时滞的情况,分析了DNA损伤强度和PDCD5表达水平对P53动力学的影响。分岔分析显示,在没有时滞时,P53表达水平随着PDCD5表达的升高呈现出单稳态,振荡和高稳态的动力学,而时滞会扩大P53振荡的范围。同时通过能量面分析了P53动力学的稳定性。本文所获得的结果对DNA损伤后P53动力学的调控起到一定的指导作用。

The dynamics of tumor suppressor protein p53plays an important role in cell fate after stresses.The dynamics of p53is closely related to the intensity of DNA damage and the protein expression level in p53signaling pathway.Recent studies have considered the regulation of protein PDCD5on p53signaling pathway and analyzed its effect on p53dynamics,but ignored the role of gene transcription and mRNA translation delay in the pathway.In this paper,we focus on p53signal pathway model with time delays and PDCD5,and explore the effects of DNA damage intensity and PDCD5expression level on the dynamics of p53in the presence or absence of time delay,respectively.Bifurcation analyses show that the expression level of p53present a low stable steady state,oscillation and high steady state with the increase of PDCD5expression for no time delay.While the time delay enlarges the range of p53oscillation.The stability of these dynamics are analyzed by the potential landscapes.The results obtained in this paper will play aguiding role in the regulation of p53dynamics after DNA damage.