Dynamical Analyses Of P53 Signaling Pathway With Time Delay

Cancer is not only a major challenge in medicine,but also an urgent problem for human beings.When the double helix base mutation and heterotopia of the genetic material DNA occur,it will cause the change of the genetic material DNA and lead to the formation of cancer.In this paper,we start with an important tumor suppressor protein p53 and based on a p53 gene regulatory network composed of p53 core regulator ATM,Wip1 and Mdm2,the effect of time delays in transcription and translation of Mdm2 and Wip1 gene expression on p53 dynamics are investigated through stability theory,bifurcation analysis and energy surface analysis.The details are as follows:In the first chapter,we briefly describe the research background,research progress at home and abroad,and the research content and results of this paper.In the second chapter,the types of singularity and Hill function are given.In the third chapter,for the model of PDCD5 regulating p53 signal pathway with time delay,the effects of DNA damage intensity and PDCD5 expression level on p53 dynamics were analyzed with or without time delay.The results show that for any DNA damage intensity without time delay,the expression level of P53 p presents the dynamics of monostable,oscillatory and high steady state with the increase of PDCD5 expression,the time delay will enlarge the range of P53 p oscillation.In the fourth chapter,a five dimensional comprehensive mathematical model of p53 gene regulatory network with two time delays and negative feedback loops is established.The critical value of Hopf bifurcation induced by time delay is analyzed theoretically,At the same time,the Hopf bifurcation induced by time delay is studied by numerical simulation.The results show that with the increase of time delay,the system will switch from stable steady state to unstable steady state,thus driving p53 to produce oscillation.In the last chapter,summarize the full text and expectations for future work.