Bifurcation analysis and potential landscapes of the p53-mdm2 module regulated by the co-activator programmed cell death 5

DOI10.1063/1.4934967zbMATH Open1374.92037arXiv1503.08261OpenAlexW1940491336WikidataQ50762805 ScholiaQ50762805MaRDI QIDQ4591789FDOQ4591789

Authors: Yuanhong Bi, Zhuoqin Yang, Changjing Zhuge, Jinzhi Lei 

Publication date: 17 November 2017

Published in: Chaos: An Interdisciplinary Journal of Nonlinear Science (Search for Journal in Brave)

Abstract: 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.

Full work available at URL: https://arxiv.org/abs/1503.08261

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zbMATH Keywords

Hopf bifurcationp53-mdm2 moduleprogrammed cell death 5

Mathematics Subject Classification ID

Biochemistry, molecular biology (92C40) Cell biology (92C37)

Cites Work

• Simulating, Analyzing, and Animating Dynamical Systems
• Elements of applied bifurcation theory.
• PDCD5 functions as a regulator of p53 dynamics in the DNA damage response

Cited In (6)

• Multiple time delays induced dynamics of p53 gene regulatory network
• Stability and bifurcation analyses of p53 gene regulatory network with time delay
• PDCD5 functions as a regulator of p53 dynamics in the DNA damage response
• Modeling the roles of 14-3-3 σ and Wip1 in p53 dynamics and programmed cell death*
• Construction of a Waddington-like landscape model that can guide clinical exploration of p53-dynamics-activating parameters in the face of divergent p53 dynamics
• Bifurcation and Potential Landscape of p53 Dynamics Depending on PDCD5 Level and ATM Degradation Rate

Uses Software

• XPPAUT

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