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In this paper, the stability and bifurcation of a two–dimensional p53 gene regulatory network without and with time delay are taken into account by rigorous theoretical analyses and numerical simulations. In the absence of time delay, the existence and local stability of the positive equilibrium are considered through the Descartes' rule of signs, the determinant and trace of the Jacobian matrix, respectively. Then, the conditions for the occurrence of codimension–1 saddle–node and Hopf bifurcation are obtained with the help of Sotomayor's theorem and the Hopf bifurcation theorem, respectively, and the stability of the limit cycle induced by hopf bifurcation is analyzed through the calculation of the first Lyapunov number. Furthermore, codimension-2 Bogdanov–Takens bifurcation is investigated by calculating a universal unfolding near the cusp. In the presence of time delay, we prove that time delay can destabilize a stable equilibrium. All theoretical analyses are supported by numerical simulations. These results will expand our understanding of the complex dynamics of p53 and provide several potential biological applications. [ABSTRACT FROM AUTHOR]

In this paper, based on a p53 gene regulatory network regulated by Programmed Cell Death 5(PDCD5), a time delay in transcription and translation of Mdm2 gene expression is introduced into the network, the effects of the time delay on oscillation dynamics of p53 are investigated through stability and bifurcation analyses. The local stability of the positive equilibrium in the network is proved through analyzing the characteristic values of the corresponding linearized systems, which give the conditions on undergoing Hopf bifurcation without and with time delay, respectively. The theoretical results are verified through numerical simulations of time series, characteristic values and potential landscapes. Furthermore, combined effect of time delay and several typical parameters in the network on oscillation dynamics of p53 are explored through two-parameter bifurcation diagrams. The results show p53 reaches a lower stable steady state under smaller PDCD5 level, the production rates of p53 and Mdm2 while reaches a higher stable steady state under these larger ones. But the case is the opposite for the degradation rate of p53. Specially, p53 oscillates at a smaller Mdm2 degradation rate, but a larger one makes p53 reach a low stable steady state. Besides, moderate time delay can make the steady state switch from stable to unstable and induce p53 oscillation for moderate value of these parameters. Theses results reveal that time delay has a significant impact on p53 oscillation and may provide a useful insight into developing anti-cancer therapy. [ABSTRACT FROM AUTHOR]

The dynamics of p53 play important roles in the regulation of cell fate decisions in response to various stresses, and programmed cell death 5 (PDCD5) functions as a co-activator of p53 that modulates p53 dynamics. In the present paper, we investigated how p53 dynamics are modulated by PDCD5 during the deoxyribose nucleic acid damage response using methods of bifurcation analysis and potential landscape. Our results revealed that p53 activities display rich dynamics under different PDCD5 levels, including monostability, bistability with two stable steady states, oscillations, and the coexistence of a stable steady state (or two states) and an oscillatory state. The physical properties of the p53 oscillations were further demonstrated by the potential landscape in which the potential force attracts the system state to the limit cycle attractor, and the curl flux force drives coherent oscillation along the cyclic trajectory. We also investigated the efficiency with which PDCD5 induced p53 oscillations. We show that Hopf bifurcation can be induced by increasing the PDCD5 efficiency and that the system dynamics exhibited clear transition features in both barrier height and energy dissipation when the efficiency was close to the bifurcation point.