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Biophysical Chemistry 134 (2008) 93-100

Mad2 binding is not sufficient for complete Cdc20 sequestering in mitotic transition control (an in silico study)

Bashar Ibrahim, Peter Dittrich, Stephan Diekmann, Eberhard Schmitt

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Related Publication
  • Mad2 binding is not sufficient for complete Cdc20 sequestering in mitotic transition control (an in silico study).
  • Ibrahim B, Dittrich P, Diekmann S, Schmitt E
  • Biophysical chemistry , 4/ 2008 , Volume 134 , pages: 93-100 , PubMed ID: 18295960
  • Bio Systems Analysis Group, Institute of Computer Science, Friedrich-Schiller-University Jena, Ernst-Abbe-Platz 1-4, D-07743 Jena, Germany.
  • For successful mitosis, metaphase has to be arrested until all centromeres are properly attached. The onset of anaphase, which is initiated by activating the APC, is controlled by the spindle assembly checkpoint (M)SAC. Mad2, which is a constitutive member of the (M)SAC, is supposed to inhibit the activity of the APC by sequestering away its co-activator Cdc20. Mad1 recruits Mad2 to unattached kinetochores and is compulsory for the establishment of the Mad2 and Cdc20 complexes. Recently, based on results from in vivo and in vitro studies, two biochemical models were proposed: the Template and the Exchange model. Here, we derive a mathematical description to compare the dynamical behaviour of the two models. Our simulation analysis supports the Template model. Using experimentally determined values for the model parameters, the Cdc20 concentration is reduced down to only about half. Thus, although the Template model displays good metaphase-to-anaphase switching behaviour, it is not able to completely describe (M)SAC regulation. This situation is neither improved by amplification nor by p31(comet) inhibition. We speculate that either additional reaction partners are required for total inhibition of Cdc20 or an extended mechanism has to be introduced for (M)SAC regulation.
Submitter of the first revision: Bashar Ibrahim
Submitter of this revision: Bashar Ibrahim
Modellers: Bashar Ibrahim

Metadata information

BioModels Database MODEL1667525941
BioModels Database BIOMD0000000194
PubMed 18295960
Taxonomy Homo sapiens

Curation status


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Model files

BIOMD0000000194_url.xml SBML L2V3 representation of Ibrahim2008_Cdc20_Sequestring_Template_Model 15.84 KB Preview | Download

Additional files

BIOMD0000000194-biopax2.owl Auto-generated BioPAX (Level 2) 11.33 KB Preview | Download
BIOMD0000000194-biopax3.owl Auto-generated BioPAX (Level 3) 15.77 KB Preview | Download
BIOMD0000000194.m Auto-generated Octave file 3.87 KB Preview | Download
BIOMD0000000194.pdf Auto-generated PDF file 167.22 KB Preview | Download
BIOMD0000000194.png Auto-generated Reaction graph (PNG) 27.67 KB Preview | Download
BIOMD0000000194.sci Auto-generated Scilab file 67.00 Bytes Preview | Download
BIOMD0000000194.svg Auto-generated Reaction graph (SVG) 10.12 KB Preview | Download
BIOMD0000000194.vcml Auto-generated VCML file 25.31 KB Preview | Download
BIOMD0000000194.xpp Auto-generated XPP file 2.20 KB Preview | Download
BIOMD0000000194_urn.xml Auto-generated SBML file with URNs 17.57 KB Preview | Download

  • Model originally submitted by : Bashar Ibrahim
  • Submitted: Sep 19, 2008 5:32:34 PM
  • Last Modified: Sep 23, 2009 6:09:50 PM
  • Version: 2 public model Download this version
    • Submitted on: Sep 23, 2009 6:09:50 PM
    • Submitted by: Bashar Ibrahim
    • With comment: Current version of Ibrahim2008_Cdc20_Sequestring_Template_Model
  • Version: 1 public model Download this version
    • Submitted on: Sep 19, 2008 5:32:34 PM
    • Submitted by: Bashar Ibrahim
    • With comment: Original import of Template Model

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: Variable used inside SBML models

Reactions Rate Parameters
Mad1_CMad2 + OMad2 => Mad1_CMad2_OMad2 Cytoplasm*(u*alpha_T*Mad1_CMad2*OMad2-beta_T*Mad1_CMad2_OMad2) beta_T = 0.2 per second; alpha_T = 200000.0 liter per mole per second; u = 1.0 dimensionless
Cdc20_CMad2 => Cdc20 + OMad2 Cytoplasm*eta_T*Cdc20_CMad2 eta_T = 0.01 per second
Mad1_CMad2_OMad2 + Cdc20 => Mad1_CMad2 + Cdc20_CMad2 Cytoplasm*u*gamma_T*Mad1_CMad2_OMad2*Cdc20 gamma_T = 1.0E9 liter per mole per second; u = 1.0 dimensionless
Curator's comment:
(added: 19 Sep 2008, 17:31:58, updated: 19 Sep 2008, 17:31:58)
Reproduction of fig 2b using SBML ODE Solver for integration and Xmgrace for plotting