College of Nuclear Science and Technology, Beijing Normal University, Beijing 100875, China.
J Theor Biol. 2011 Jan 21;269(1):104-8. doi: 10.1016/j.jtbi.2010.10.009. Epub 2010 Oct 23.
The p53 feedback loop can induce cellular senescence, cell cycle arrest and apoptosis in response to various stresses, including DNA damage, hypoxia and nutrient deprivation. Using a stochastic model of the negative feedback circuit involving p53 and its inhibitor Mdm2, we present the different oscillatory dynamics at the single-cell and population-cell levels as described in the experiments, and the resonant nature of the oscillations is captured. The stationary distributions of protein populations are characterized by non-Gaussian nature which is due to the interplay between time delay and nonlinearity of reactions.
p53 反馈回路可以响应各种应激,包括 DNA 损伤、缺氧和营养剥夺,诱导细胞衰老、细胞周期停滞和细胞凋亡。我们使用涉及 p53 和其抑制剂 Mdm2 的负反馈回路的随机模型,展示了如实验所描述的单细胞和群体细胞水平的不同振荡动力学,并捕捉到了振荡的共振性质。蛋白质群体的静态分布表现出非高斯性质,这是由于反应的时滞和非线性相互作用所致。