NDLI: Multi-scale modeling of cell survival and death mediated by the p53 network: a systems pharmacology framework.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Wang, Yuan Guo, Zihu Chen, Xuetong Zhang, Wenjuan Lu, Aiping Wang, Yonghua
Description	Country affiliation: China Author Affiliation: Wang Y ( Lab of Systems Pharmacology, Center of Bioinformatics, College of Life Science, Northwest A&F University, Yangling, Shaanxi 712100, China. yh_wang@nwsuaf.edu.cn.)
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.
File Format	HTM / HTML
ISSN	1742206X
Issue Number	11
Volume Number	11
e-ISSN	17422051
Journal	Molecular BioSystems
Language	English
Publisher	Royal Society of Chemistry
Publisher Date	2015-11-01
Publisher Place	Great Britain (UK)
Access Restriction	Subscribed
Subject Keyword	Discipline Molecular Biology Discipline Biochemistry Gene Regulatory Networks Models, Biological Systems Biology Tumor Suppressor Protein P53 Metabolism Cell Death Cell Lineage Cell Survival Computer Simulation Dna Damage Kinetics Stress, Physiological Journal Article Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Molecular Biology Biotechnology

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