Bifurcation analysis and potential landscape of the p53-Mdm2 oscillator regulated by the co-activator PDCD5
Dynamics of p53 is known to play important roles in the regulation of cell fate decisions in response to various stresses, and PDCD5 functions as a co-activator of p53 to modulate the p53 dynamics. In the present paper, we investigate how p53 dynamics are modulated by PDCD5 during the DNA damage response using methods of bifurcation analysis and potential landscape. Our results reveal that p53 activities can display rich dynamics under different PDCD5 levels, including monostability, bistability with two stable steady states, oscillations, and co-existence of a stable steady state and an oscillatory state. Physical properties of the p53 oscillations are further shown by the potential landscape, in which the potential force attracts the system state to the limit cycle attractor, and the curl flux force drives the coherent oscillation along the cyclic. We also investigate the effect of PDCD5 efficiency on inducing the p53 oscillations. We show that Hopf bifurcation is induced by increasing the PDCD5 efficiency, and the system dynamics show clear transition features in both barrier height and energy dissipation when the efficiency is close to the bifurcation point. This study provides a global picture of how PDCD5 regulates p53 dynamics via the interaction with the p53-Mdm2 oscillator and can be helpful in understanding the complicate p53 dynamics in a more complete p53 pathway.
Code (0)
등록된 구현이 없습니다.
Similar Papers 제목 키워드 기반
Hopf-type neurons increase input-sensitivity by forming forcing-coupled ensembles
Astounding properties of biological sensors can often be mapped onto a dynamical system in the vicinity a bifurcation. For mammalian hearing, a Hopf bifurcation description has been shown to work across a whole range of …
SensitivityVocal Bursts Type PredictionMoment Closure Stability Analysis of Stochastic Reaction Networks with Oscillatory Dynamics
Biochemical reactions with oscillatory behavior play an essential role in synthetic biology at the microscopic scale. Although a robust stability theory for deterministic chemical oscillators in the macroscopic limit exi…
Dynamics of ERK regulation in the processive limit
We consider a model of extracellular signal-regulated kinase (ERK) regulation by dual-site phosphorylation and dephosphorylation, which exhibits bistability and oscillations, but loses these properties in the limit in wh…
Gene expression noise accelerates the evolution of a biological oscillator
Gene expression is a biochemical process, where stochastic binding and un-binding events naturally generate fluctuations and cell-to-cell variability in gene dynamics. These fluctuations typically have destructive conseq…
Nonlinear Robust Periodic Output Regulation of Minimum Phase Systems
In linear systems theory it's a well known fact that a regulator given by the cascade of an oscillatory dynamics, driven by some regulated variables, and of a stabiliser stabilising the cascade of the plant and of the os…
Blocking