Dynamic behavior of P53-Mdm2-Wip1 gene regulatory network under the influence of time delay and noise

Abstract

<abstract><p>The tumor suppressor protein P53 can regulate the cell cycle, thereby preventing cell abnormalities. In this paper, we study the dynamic characteristics of the P53 network under the influence of time delay and noise, including stability and bifurcation. In order to study the influence of several factors on the concentration of P53, bifurcation analysis on several important parameters is conducted; the results show that the important parameters could induce P53 oscillations within an appropriate range. Then we study the stability of the system and the existing conditions of Hopf bifurcation by using Hopf bifurcation theory with time delays as the bifurcation parameter. It is found that time delay plays a key role in inducing Hopf bifurcation and regulating the period and amplitude of system oscillation. Meanwhile, the combination of time delays can not only promote the oscillation of the system but it also provides good robustness. Changing the parameter values appropriately can change the bifurcation critical point and even the stable state of the system. In addition, due to the low copy number of the molecules and the environmental fluctuations, the influence of noise on the system is also considered. Through numerical simulation, it is found that noise not only promotes system oscillation but it also induces system state switching. The above results may help us to further understand the regulation mechanism of the P53-Mdm2-Wip1 network in the cell cycle.</p></abstract>