共激活剂PDCD5调控的p53-Mdm2振子的分岔分析和潜在景观
Bifurcation analysis and potential landscape of the p53-Mdm2 oscillator regulated by the co-activator PDCD5
摘要：
已知p53的动力学在响应于各种应激的细胞命运决定的调节中起重要作用，并且PDCD 5作为p53的共激活剂发挥作用以调节p53动力学。在本文中，我们研究如何p53动力学的DNA损伤反应过程中PDCD 5调制的分岔分析和潜在的景观的方法。我们的研究结果表明，p53活性在不同的PDCD 5水平下可以显示出丰富的动态，包括单稳态，双稳态与两个稳定的稳态，振荡，以及共存的稳定的稳态和振荡状态。p53振荡的物理性质进一步显示的潜在景观，其中的潜在力量吸引系统状态的极限环吸引子，和旋度通量力驱动的相干振荡沿循环。我们还研究了PDCD 5效率对诱导p53振荡的影响。结果表明，随着PDCD 5效率的提高，系统发生了Hopf分岔，当效率接近分岔点时，系统动力学在势垒高度和能量耗散两个方面都表现出明显的过渡特征.这项研究提供了一个全面的图片PDCD 5如何通过与p53-Mdm 2振荡器的相互作用，调节p53的动力学，可以帮助理解复杂的p53动力学在一个更完整的p53通路。
英文摘要：
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.
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