DNA损伤致p53-Mdm2相互作用的非线性动力学模型(英文)

A Nonlinear Dynamical Model for Studying DNA Damage-induced p53-Mdm2 Interaction

摘要: p53-Mdm2相互作用在DNA损伤的细胞响应方面起着非常重要的作用。最新实验结果表明，在受到各种辐射损伤而引起DNA损伤后，细胞中的p53蛋白浓度在单体细胞和群体细胞情况下，表现为非衰减振荡和衰减振荡两种不同的动力学行为。通过研究p53 -Mdm2负反馈回路的非线性动力学，分析了各种（特别是DNA损伤，p53和Mdm2浓度三者之间的）动力学关系，提出了一个能同时描述这两种不同动力学行为的非线性模型。 Exploring the nonlinear dynamics of the negative feedback loop composed of p53 and Mdm2 proteins, we propose a signal-response model to study the dynamical mechanism of the different oscillatory behaviors for the activities of p53 and Mdm2 proteins both in individual and population of cells. It is shown that the sustained and damped oscillatory dynamics could be described in a unified way when the dynamics of damage-derived signal is properly introduced.

Abstract: Exploring the nonlinear dynamics of the negative feedback loop composed of p53 and Mdm2 proteins, we propose a signal-response model to study the dynamical mechanism of the different oscillatory behaviors for the activities of p53 and Mdm2 proteins both in individual and population of cells. It is shown that the sustained and damped oscillatory dynamics could be described in a unified way when the dynamics of damage-derived signal is properly introduced.