ATM磷酸化速率调控p53动力学的分岔分析

Bifurcation of p53 Dynamics Regulated by ATM Phosphorylation Rate

压力后细胞内p53的不同动力学决定不同的细胞命运。本文基于包含ATM(Ataxia Telangiectasia Mutated)感应模块和PDCD5(Programmed Cell Death 5)调控p53-Mdm2(Murine Double Minute 2)振子的基因调控网络,利用分岔分析,探讨了在不同PDCD5表达水平下,ATM磷酸化速率对p53动力学的影响。结果显示,参数的变化可使系统产生平衡点的鞍结分岔,霍普夫分岔,同宿分岔,鞍结同宿分岔以及极限环的鞍结分岔,这些分岔使p53呈现单稳态,双稳态和三稳态的动力学。该研究表明PDCD5表达水平和ATM磷酸化速率对p53动力学有重要的影响,对了解压力后细胞命运起到一定理论指导作用。

Different dynamics of p53 in cells after stress determine different cell fates.Based on a gene regulation network model including ATM(Ataxia Telangiectasia Mutated)sensing module and PDCD5(Programmed Cell Death 5)regulating p53-MDM2(Murine Double Minute 2)oscillator,the effect of ATM phosphorylation rate on p53 dynamics at different PDCD5 expression levels are discussed by bifurcation analysis.The results show that the variation of parameters can induce saddle-node bifurcation of equilibrium point,Hopf bifurcation,homoclinic bifurcation,saddle node homoclinic bifurcation and saddle-node bifurcation of limit cycle.These bifurcations make p53 show rich dynamics with monostablity,bistablity and tristablity.Our study indicates that PDCD5 expression level and ATM phosphorylation rate have important effects on p53 dynamics,and play a theoretical guiding role in understanding cell fate after stress.