title: Multi-scale modeling of cell survival and death mediated by the p53 network: a systems pharmacology framework.
abstract: The determination of cell fate is a key regulatory process for the development of complex organisms that are controlled by distinct genes in mammalian cells. To interpret the decision process in a rigorous, analytical framework, we performed a multi-scale simulation of cell fate decision mediated by the p53 regulatory network in a systems pharmacology framework. The model treats fate determination as a gradual response to stress that delays the initiation of apoptosis to give the cell an opportunity to survive. The newly proposed two-factor model: DNA-p53 coupling explains the phenomenon of the existing biological responses to stress damage for the p53 regulatory network. In addition, the model also reveals that the cell survival rate can be improved by lowering the p53 level in a feedback network to increase its robustness for external stimuli. The present work not only deepens our understanding of cell fate determination, but also provides a theoretical basis for rational drug discovery and development.
authors: Lab of Systems Pharmacology, Center of Bioinformatics, College of Life Science, Northwest A&F University, Yangling, Shaanxi 712100, China. yh_wang@nwsuaf.edu.cn.
authors: Yuan
authors: Y
authors: Wang
authors: Zihu
authors: Z
authors: Guo
authors: Xuetong
authors: X
authors: Chen
authors: Wenjuan
authors: W
authors: Zhang
authors: Aiping
authors: A
authors: Lu
authors: Yonghua
authors: Y
authors: Wang
mesh_terms: D016923:Cell Death; D019070:Cell Lineage; D002470:Cell Survival; D003198:Computer Simulation; D004249:DNA Damage; D053263:Gene Regulatory Networks; D007700:Kinetics; D008954:Models, Biological; D013312:Stress, Physiological; D049490:Systems Biology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D016159:Tumor Suppressor Protein p53