Ciliberto2005 - Steady states and oscillations in the p53/Mdm2 network

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Model Identifier
Short description
Its a mathematial model studying steady state and oscialltions in p53-MDM2 network triggered by IR induced DNA Damage.
Related Publication
  • Steady states and oscillations in the p53/Mdm2 network.
  • Ciliberto A, Bela Novak, Tyson JJ
  • Cell cycle (Georgetown, Tex.) , 3/ 2005 , Volume 4 , Issue 3 , pages: 488-493 , PubMed ID: 15725723
  • Molecular Network Dynamics Research Group of Hungarian Academy of Sciences, Budapest University of Technology and Economics, Budapest, Hungary.
  • p53 is activated in response to events compromising the genetic integrity of a cell. Recent data show that p53 activity does not increase steadily with genetic damage but rather fluctuates in an oscillatory fashion. Theoretical studies suggest that oscillations can arise from a combination of positive and negative feedbacks or from a long negative feedback loop alone. Both negative and positive feedbacks are present in the p53/Mdm2 network, but it is not known what roles they play in the oscillatory response to DNA damage. We developed a mathematical model of p53 oscillations based on positive and negative feedbacks in the p53/Mdm2 network. According to the model, the system reacts to DNA damage by moving from a stable steady state into a region of stable limit cycles. Oscillations in the model are born with large amplitude, which guarantees an all-or-none response to damage. As p53 oscillates, damage is repaired and the system moves back to a stable steady state with low p53 activity. The model reproduces experimental data in quantitative detail. We suggest new experiments for dissecting the contributions of negative and positive feedbacks to the generation of oscillations.
Krishna Kumar Tiwari

Metadata information

PubMed 15725723
Taxonomy Homo sapiens
Mathematical Modelling Ontology Ordinary differential equation model
Brenda Tissue Ontology epithelial cell

Curation status

Name Description Size Actions

Model files

Ciliberto2005.xml SBML L2V4 file for the curated model 98.91 KB Preview | Download

Additional files

p53-Mdm2.ode XPP file provided by Author (on request) 1.22 KB Preview | Download
Ciliberto2005.sedml SEDML file for the curated model 4.75 KB Preview | Download
Ciliberto2005.cps COPASI 4.30(Build240) file for the model 157.75 KB Preview | Download

  • Model originally submitted by : Krishna Kumar Tiwari
  • Submitted: 14-Apr-2021 16:26:16
  • Last Modified: 14-Apr-2021 16:26:16
  • Version: 2 public model Download this version
    • Submitted on: 14-Apr-2021 16:26:16
    • Submitted by: Krishna Kumar Tiwari
    • With comment: Automatically added model identifier BIOMD0000001006
: Variable used inside SBML models

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Curator's comment:
(added: 14 Apr 2021, 16:25:39, updated: 14 Apr 2021, 16:25:39)
Literature figure 2A,B,C is reproduced in the model. Model encoded, simulated and annotated using COPASI 4.30 (Build240). Simulation figures are generated using COPASI.