Document Detail


A theoretical model for p53 dynamics: identifying optimal therapeutic strategy for its activation and stabilization.
MedLine Citation:
PMID:  19844169     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The activation and stabilization of tumor suppressor p53 are very important in preventing cells from becoming cancerous. Hence, many experimental works have been carried out to investigate p53's dynamics through its interactions with other proteins and its therapeutic applications for the treatment of cancers. In this work, by analyzing a theoretical model, we attempt to search for an optimal therapeutic strategy that guarantees the activation and stabilization of p53. For this purpose, we introduce a new mathematical model including oncogene activation and ARF, which are recognized as crucial for tumor suppression but have not yet been considered in most theoretical works. Through mathematical modeling and numerical simulations, we confirm several important properties of p53 dynamics: the role of the oncogene-mediated activation of ARF as an important factor for the activation and stabilization of p53, the necessity of time delays in negative feedback loops to guarantee sustained p53 oscillations, and the digital behavior of p53 pulses. Furthermore, we propose that the binding of ARF to Mdm2 and enhancing the degradation of Mdm2 is an efficient strategy for therapeutic targeting, which may assure the activation and stabilization of p53.
Authors:
Do-Hyun Kim; Kyoohyoung Rho; Sunghoon Kim
Related Documents :
14525089 - Period locking due to delayed feedback in a laser with saturable absorber.
21947049 - Evaluation of kerr constant of blue-phase liquid crystals by measuring off-axis retarda...
21682519 - On the mechanism of the highly viscous flow.
20173829 - Dispersion engineering with leaky-mode resonant photonic lattices.
19015679 - Wavelength-transparent, stimulated-brillouin-scattering slow light using cross-gain-mod...
17078609 - Controlled excitations of the belousov-zhabotinsky reaction: experimental procedures.
24105519 - Widely tunable vernier ring laser on hybrid silicon.
24269529 - Ultrasound signal wavelet analysis to quantify the microstructures of normal and frozen...
1705219 - A theoretical calculation of the electric field induced in the cortex during magnetic s...
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-11-08
Journal Detail:
Title:  Cell cycle (Georgetown, Tex.)     Volume:  8     ISSN:  1551-4005     ISO Abbreviation:  Cell Cycle     Publication Date:  2009 Nov 
Date Detail:
Created Date:  2009-11-10     Completed Date:  2010-03-01     Revised Date:  2011-11-02    
Medline Journal Info:
Nlm Unique ID:  101137841     Medline TA:  Cell Cycle     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3707-16     Citation Subset:  IM    
Affiliation:
Information Center for Bio-Pharmacological Network, Seoul National University, Suwon, Korea.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Cell Cycle Proteins / metabolism
Computer Simulation
Cyclin-Dependent Kinase Inhibitor p16 / metabolism*
DNA-Binding Proteins / metabolism
Drug Discovery / methods*
Gene Expression Regulation / physiology*,  radiation effects
Humans
Models, Biological*
Neoplasms / drug therapy*
Oscillometry
Phosphoprotein Phosphatases / metabolism
Protein-Serine-Threonine Kinases / metabolism
Proto-Oncogene Proteins c-mdm2 / metabolism*
Radiation, Ionizing
Tumor Suppressor Protein p53 / metabolism*,  therapeutic use
Tumor Suppressor Proteins / metabolism
Chemical
Reg. No./Substance:
0/Cell Cycle Proteins; 0/Cyclin-Dependent Kinase Inhibitor p16; 0/DNA-Binding Proteins; 0/Tumor Suppressor Protein p53; 0/Tumor Suppressor Proteins; EC 2.7.1.11/checkpoint kinase 2; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.1/ataxia telangiectasia mutated protein; EC 3.1.3.16/Phosphoprotein Phosphatases; EC 3.1.3.16/protein phosphatase 2C; EC 6.3.2.19/MDM2 protein, human; EC 6.3.2.19/Proto-Oncogene Proteins c-mdm2

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  AMPK: Evidence for an energy-sensing cytokinetic tumor suppressor.
Next Document:  Protective roles of matrix metalloproteinases: from mouse models to human cancer.