Pomerening2005- Model of the Xenopus Cdc2/APC System

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Model Identifier
MODEL2005150001
Short description
The cell-cycle oscillator includes an essential negative-feedback loop: Cdc2 activates the anaphase-promoting complex (APC), which leads to cyclin destruction and Cdc2 inactivation. Under some circumstances, a negative-feedback loop is sufficient to generate sustained oscillations. However, the Cdc2/APC system also includes positive-feedback loops, whose functional importance we now assess. We show that short-circuiting positive feedback makes the oscillations in Cdc2 activity faster, less temporally abrupt, and damped. This compromises the activation of cyclin destruction and interferes with mitotic exit and DNA replication. This work demonstrates a systems-level role for positive-feedback loops in the embryonic cell cycle and provides an example of how oscillations can emerge out of combinations of subcircuits whose individual behaviors are not oscillatory. This work also underscores the fundamental similarity of cell-cycle oscillations in embryos to repetitive action potentials in pacemaker neurons, with both systems relying on a combination of negative and positive-feedback loops.
Format
SBML (L2V4)
Related Publication
  • Systems-level dissection of the cell-cycle oscillator: bypassing positive feedback produces damped oscillations.
  • Pomerening JR, Kim SY, Ferrell JE Jr
  • Cell , 8/ 2005 , Volume 122 , Issue 4 , pages: 565-578 , PubMed ID: 16122424
  • Department of Molecular Pharmacology, Stanford University School of Medicine, Stanford, California 94305, USA. pomereni@stanford.edu
  • The cell-cycle oscillator includes an essential negative-feedback loop: Cdc2 activates the anaphase-promoting complex (APC), which leads to cyclin destruction and Cdc2 inactivation. Under some circumstances, a negative-feedback loop is sufficient to generate sustained oscillations. However, the Cdc2/APC system also includes positive-feedback loops, whose functional importance we now assess. We show that short-circuiting positive feedback makes the oscillations in Cdc2 activity faster, less temporally abrupt, and damped. This compromises the activation of cyclin destruction and interferes with mitotic exit and DNA replication. This work demonstrates a systems-level role for positive-feedback loops in the embryonic cell cycle and provides an example of how oscillations can emerge out of combinations of subcircuits whose individual behaviors are not oscillatory. This work also underscores the fundamental similarity of cell-cycle oscillations in embryos to repetitive action potentials in pacemaker neurons, with both systems relying on a combination of negative and positive-feedback loops.
Contributors
Ahmad Zyoud

Metadata information

hasTaxon
Taxonomy Xenopus laevis
hasProperty
Mathematical Modelling Ontology Ordinary differential equation model
NCIt Cyclin
Gene Ontology cell cycle
isDescribedBy

Curation status
Non-curated


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Model files

Pomerening2005.xml SBML L2V4 Pomerening2005- Model of the Xenopus Cdc2/APC System 123.44 KB Preview | Download

Additional files

Pomerening2005.cps COPASI version 4.27 (Build 217) Pomerening2005- Model of the Xenopus Cdc2/APC System 212.61 KB Preview | Download

  • Model originally submitted by : Ahmad Zyoud
  • Submitted: 15-May-2020 17:59:10
  • Last Modified: 22-May-2020 04:38:59
Revisions
  • Version: 2 public model Download this version
    • Submitted on: 22-May-2020 04:38:59
    • Submitted by: Ahmad Zyoud
    • With comment: Model revised without commit message
  • Version: 1 public model Download this version
    • Submitted on: 15-May-2020 17:59:10
    • Submitted by: Ahmad Zyoud
    • With comment: Import of Pomerening2005- Model of the Xenopus Cdc2/APC System
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