ibrahim4

R6

Mad1_CMad2 + OMad2 = Mad1_CMad2_OMad2

R7

Mad1_CMad2_OMad2 + Cdc20 > Mad1_CMad2 + Cdc20_CMad2

R8

Cdc20_CMad2 > Cdc20 + OMad2

Global parameters

mt_attachment

Trigger: gt(time, 2000)

Delay:

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  • u = const_val_0

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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
Biophys. Chem. 2008; 134 : 93
Abstract
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.
The SBML for this model was obtained from the BioModels database (BioModels ID: BIOMD0000000194) Biomodels notes: Reproduction of fig 2b using SBML ODE Solver for integration and Xmgrace for plotting. JWS Online curation: This model was curated by reproducing the figures as described in the BioModels Notes. No additional changes were made.