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Modeling the basal dynamics of p53 system.

BACKGROUNDThe tumor suppressor p53 has become one of most investigated genes. Once activated by stress, p53 leads to cellular responses such as cell cycle arrest and apoptosis. METHODOLOGY/PRINCIPAL FINDINGSMost previous models have ignored the basal dynamics of p53 under nonstressed conditions. To... Full description

Journal Title: PloS one 2011, Vol.6(11), p.e27882
Main Author: Sun, Tingzhe
Other Authors: Yang, Weiwei , Liu, Jing , Shen, Pingping
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 1932-6203 ; DOI: 10.1371/journal.pone.0027882
Link: http://search.proquest.com/docview/906154613/?pq-origsite=primo
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title: Modeling the basal dynamics of p53 system.
format: Article
creator:
  • Sun, Tingzhe
  • Yang, Weiwei
  • Liu, Jing
  • Shen, Pingping
subjects:
  • Ataxia Telangiectasia Mutated Proteins–Metabolism
  • Cell Cycle–Metabolism
  • Cell Cycle Proteins–Metabolism
  • Computer Simulation–Metabolism
  • Cyclin-Dependent Kinase Inhibitor P21–Metabolism
  • DNA Damage–Genetics
  • DNA-Binding Proteins–Metabolism
  • Humans–Metabolism
  • Models, Biological–Metabolism
  • Models, Theoretical–Metabolism
  • Phosphoprotein Phosphatases–Metabolism
  • Phosphorylation–Metabolism
  • Protein Phosphatase 2c–Metabolism
  • Protein Processing, Post-Translational–Metabolism
  • Protein-Serine-Threonine Kinases–Metabolism
  • Signal Transduction–Metabolism
  • Tumor Suppressor Protein P53–Metabolism
  • Tumor Suppressor Proteins–Metabolism
  • Cdkn1a Protein, Human
  • Cell Cycle Proteins
ispartof: PloS one, 2011, Vol.6(11), p.e27882
description: BACKGROUNDThe tumor suppressor p53 has become one of most investigated genes. Once activated by stress, p53 leads to cellular responses such as cell cycle arrest and apoptosis. METHODOLOGY/PRINCIPAL FINDINGSMost previous models have ignored the basal dynamics of p53 under nonstressed conditions. To explore the basal dynamics of p53, we constructed a stochastic delay model by incorporating two negative feedback loops. We found that protein distribution of p53 under nonstressed condition is highly skewed with a fraction of cells showing high p53 levels comparable to those observed under stressed conditions. Under nonstressed conditions, asynchronous and spontaneous p53 pulses are triggered by basal DNA double strand breaks produced during normal cell cycle progression. The first peaking times show a predominant G1 distribution while the second ones are more widely distributed. The spontaneous pulses are triggered by an excitable mechanism. Once initiated, the amplitude and duration of pulses...
language: eng
source:
identifier: E-ISSN: 1932-6203 ; DOI: 10.1371/journal.pone.0027882
fulltext: fulltext
issn:
  • 19326203
  • 1932-6203
url: Link


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titleModeling the basal dynamics of p53 system.
creatorSun, Tingzhe ; Yang, Weiwei ; Liu, Jing ; Shen, Pingping
contributorSun, Tingzhe (correspondence author) ; Sun, Tingzhe (record owner)
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identifierE-ISSN: 1932-6203 ; DOI: 10.1371/journal.pone.0027882
subjectAtaxia Telangiectasia Mutated Proteins–Metabolism ; Cell Cycle–Metabolism ; Cell Cycle Proteins–Metabolism ; Computer Simulation–Metabolism ; Cyclin-Dependent Kinase Inhibitor P21–Metabolism ; DNA Damage–Genetics ; DNA-Binding Proteins–Metabolism ; Humans–Metabolism ; Models, Biological–Metabolism ; Models, Theoretical–Metabolism ; Phosphoprotein Phosphatases–Metabolism ; Phosphorylation–Metabolism ; Protein Phosphatase 2c–Metabolism ; Protein Processing, Post-Translational–Metabolism ; Protein-Serine-Threonine Kinases–Metabolism ; Signal Transduction–Metabolism ; Tumor Suppressor Protein P53–Metabolism ; Tumor Suppressor Proteins–Metabolism ; Cdkn1a Protein, Human ; Cell Cycle Proteins
descriptionBACKGROUNDThe tumor suppressor p53 has become one of most investigated genes. Once activated by stress, p53 leads to cellular responses such as cell cycle arrest and apoptosis. METHODOLOGY/PRINCIPAL FINDINGSMost previous models have ignored the basal dynamics of p53 under nonstressed conditions. To explore the basal dynamics of p53, we constructed a stochastic delay model by incorporating two negative feedback loops. We found that protein distribution of p53 under nonstressed condition is highly skewed with a fraction of cells showing high p53 levels comparable to those observed under stressed conditions. Under nonstressed conditions, asynchronous and spontaneous p53 pulses are triggered by basal DNA double strand breaks produced during normal cell cycle progression. The first peaking times show a predominant G1 distribution while the second ones are more widely distributed. The spontaneous pulses are triggered by an excitable mechanism. Once initiated, the amplitude and duration of pulses...
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titleModeling the basal dynamics of p53 system.
descriptionBACKGROUNDThe tumor suppressor p53 has become one of most investigated genes. Once activated by stress, p53 leads to cellular responses such as cell cycle arrest and apoptosis. METHODOLOGY/PRINCIPAL FINDINGSMost previous models have ignored the basal dynamics of p53 under nonstressed conditions. To explore the basal dynamics of p53, we constructed a stochastic delay model by incorporating two negative feedback loops. We found that protein distribution of p53 under nonstressed condition is highly skewed with a fraction of cells showing high p53 levels comparable to those observed under stressed conditions. Under nonstressed conditions, asynchronous and spontaneous p53 pulses are triggered by basal DNA double strand breaks produced during normal cell cycle progression. The first peaking times show a predominant G1 distribution while the second ones are more widely distributed. The spontaneous pulses are triggered by an excitable mechanism. Once initiated, the amplitude and duration of pulses...
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15Signal Transduction–Metabolism
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18Cdkn1a Protein, Human
19Cell Cycle Proteins
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abstractBACKGROUNDThe tumor suppressor p53 has become one of most investigated genes. Once activated by stress, p53 leads to cellular responses such as cell cycle arrest and apoptosis. METHODOLOGY/PRINCIPAL FINDINGSMost previous models have ignored the basal dynamics of p53 under nonstressed conditions. To explore the basal dynamics of p53, we constructed a stochastic delay model by incorporating two negative feedback loops. We found that protein distribution of p53 under nonstressed condition is highly skewed with a fraction of cells showing high p53 levels comparable to those observed under stressed conditions. Under nonstressed conditions, asynchronous and spontaneous p53 pulses are triggered by basal DNA double strand breaks produced during normal cell cycle progression. The first peaking times show a predominant G1 distribution while the second ones are more widely distributed. The spontaneous pulses are triggered by an excitable mechanism. Once initiated, the amplitude and duration of pulses...
doi10.1371/journal.pone.0027882
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date2011-01-01