PDCD5调控的p53动力学分岔分析

Bifurcation Analysis of p53 Dynamics Mediated by PDCD5

肿瘤抑制蛋白p53在DNA损伤的反应中起到关键的作用.基于PDCD5(Programmed Cell Death 5)调控的p53-Mdm2振子模型,增加了药物依托泊苷(etoposide,简称ETS)引起DNA损伤进而激活ATM(ataxia telangiectasia mutated)的模块.通过分岔分析,首先探讨了PDCD5和ETS剂量调控的p53动力学.在任何ETS剂量下,随着PDCD5浓度的增加产生了超临界Hopf分岔,系统由单稳态转为振荡.其次,在确定的ETS剂量下,讨论了PDCD5和激活的ATM降解速率对p53动力学的影响.随着这两个参数的变化,p53展现出丰富的动力学,包括单稳态、两个稳定的稳态、振荡以及单稳态与振荡共存的双稳态.通过研究这些参数对p53动力学的影响,可以在理解DNA损伤后的p53信号通路调控中起到一定的指导作用.

Tumor suppressor protein p53 plays a key role in the DNA damage response. The modules with DNA damage induced by ETS and the activation of ATM are added to p53-Mdm2 os- cillator model mediated by PDCDS. Through bifurcation analysis,p53 dynamics mediated by PDCD5 and the dosage of ETS is firstly explored. The dynamics of system changes from a single steady state to oscillation due to the supercritical Hopf bifurcation with the increasing of PDCD5 level at any ETS dosage. Secondly, the effects of PDCD5 and the active ATM degradation rate on p53 dy- namics are discussed. With the change of these two parameters,p53 exhibits rich dynamics,inclu- ding a single steady state,two steady states,oscillation and the bistability with a single steady state and oscillation. These results show that the effect of these parameters on p53 dynamics is helpful for understanding the regulation of p53 signaling pathway after DNA damage.