Liu Bo, Yan Shiwei, Wang Qi
College of Nuclear Science and Technology, Beijing Normal University, Beijing 100875, PR China.
Mol Biosyst. 2011 Feb;7(2):457-63. doi: 10.1039/c0mb00133c. Epub 2010 Nov 8.
We explore one of the best-studied protein circuits in human cells, the negative feedback loop between the tumor suppressor p53 and the oncogene Mdm2 following nuclear irradiation. Using stochastic delay differential equations and the Gillespie algorithm, we illustrate the distinct oscillatory dynamics at the single-cell and population-cell levels which were found in the recent experiments. The oscillatory dynamics of p53-Mdm2 interaction appears as coherent resonance with delay and noise in individual cells. Dephasing mechanisms provide the origin of damped oscillation at the population level out of the sustained one at the single-cell level. The non-Gaussian nature of distributions of protein populations results from the interplay between time delay and nonlinearity of reaction processes. Our findings may lead to new insights related to the effects of noise and cancer therapy.
我们研究了人类细胞中研究最为深入的蛋白质回路之一，即核辐射后肿瘤抑制因子p53与癌基因Mdm2之间的负反馈回路。利用随机延迟微分方程和 Gillespie 算法，我们阐明了近期实验中在单细胞和群体细胞水平上发现的不同振荡动力学。p53-Mdm2相互作用的振荡动力学在单个细胞中表现为具有延迟和噪声的相干共振。去相位机制导致了在群体水平上从单细胞水平的持续振荡转变为阻尼振荡。蛋白质群体分布的非高斯性质源于反应过程的时间延迟和非线性之间的相互作用。我们的研究结果可能会为与噪声和癌症治疗的影响相关的新见解提供线索。
