Ibrahim2008_MCC_assembly_model_KDM

  public model
Model Identifier
BIOMD0000000193
Short description
BioSystems (2007), doi:10.1016/j.biosystems.2008.06.007

In-silico study of kinetochore control, amplification, and inhibition effects in MCC assembly


Bashar Ibrahim, Eberhard Schmitt, Peter Dittrich, Stephan Diekmann
This is the kinetochore dependent MCC model (KDM) from the article. For the kinetochore independent MCC model (KIM) replace u*k4f in R4 by k4f and u*k5f in R5 by k5f .

This model originates from BioModels Database: A Database of Annotated Published Models. It is copyright (c) 2005-2009 The BioModels Team.
For more information see the terms of use .
To cite BioModels Database, please use Le Novère N., Bornstein B., Broicher A., Courtot M., Donizelli M., Dharuri H., Li L., Sauro H., Schilstra M., Shapiro B., Snoep J.L., Hucka M. (2006) BioModels Database: A Free, Centralized Database of Curated, Published, Quantitative Kinetic Models of Biochemical and Cellular Systems Nucleic Acids Res., 34: D689-D691.

Format
SBML (L2V3)
Related Publication
  • In silico study of kinetochore control, amplification, and inhibition effects in MCC assembly.
  • Ibrahim B, Schmitt E, Dittrich P, Diekmann S
  • Bio Systems , 1/ 2009 , Volume 95 , pages: 35-50 , PubMed ID: 18675311
  • Bio Systems Analysis Group, Institute of Computer Science, Friedrich-Schiller-University Jena, Germany. ibrahim@minet.uni-jena.de
  • Eukaryotic cells rely on a surveillance mechanism, the "Spindle Assembly Checkpoint"SACM in order to ensure accurate chromosome segregation by preventing anaphase initiation until all chromosomes are correctly attached to the mitotic spindle. In different organisms, a mitotic checkpoint complex (MCC) composed of Mad2, Bub3, BubR1/Mad3, and Cdc20 inhibits the anaphase promoting complex (APC/C) to initiate promotion into anaphase. The mechanism of MCC formation and its regulation by the kinetochore are unclear. Here, we constructed dynamical models of MCC formation involving different kinetochore control mechanisms including amplification as well as inhibition effects, and analysed their quantitative properties. In particular, in this system, fast and stable metaphase to anaphase transition can only be triggered when the kinetochore controls the Bub3:BubR1-related reactions; signal amplification and inhibition play a subordinate role. Furthermore, when introducing experimentally determined parameter values into the models analysed here, we found that effective MCC formation is not combined with complete Cdc20 sequestering. Instead, the MCC might bind and completely block the APC/C. The SACM might function by an MCC:APC/C complex rearrangement.
Contributors
Bashar Ibrahim

Metadata information

is
BioModels Database MODEL1667758030
BioModels Database BIOMD0000000193
isDescribedBy
PubMed 18675311
hasTaxon
Taxonomy Homo sapiens
isVersionOf
Reactome Mitotic Spindle Checkpoint
Gene Ontology GO:0007094
isPartOf
KEGG Pathway Cell cycle - Homo sapiens (human)
Curation status
Curated
Tags
Name Description Size Actions

Model files
BIOMD0000000193_url.xml SBML L2V3 representation of Ibrahim2008_MCC_assembly_model_KDM 23.97 KB Preview | Download

Additional files
BIOMD0000000193_urn.xml Auto-generated SBML file with URNs 26.16 KB Preview | Download
BIOMD0000000193.pdf Auto-generated PDF file 186.78 KB Preview | Download
BIOMD0000000193.m Auto-generated Octave file 4.99 KB Preview | Download
BIOMD0000000193-biopax2.owl Auto-generated BioPAX (Level 2) 17.54 KB Preview | Download
BIOMD0000000193.svg Auto-generated Reaction graph (SVG) 18.03 KB Preview | Download
BIOMD0000000193.png Auto-generated Reaction graph (PNG) 48.81 KB Preview | Download
BIOMD0000000193.sci Auto-generated Scilab file 67.00 bytes Preview | Download
BIOMD0000000193-biopax3.owl Auto-generated BioPAX (Level 3) 25.76 KB Preview | Download
BIOMD0000000193.vcml Auto-generated VCML file 36.48 KB Preview | Download
BIOMD0000000193.xpp Auto-generated XPP file 3.15 KB Preview | Download

  • Model originally submitted by : Bashar Ibrahim
  • Submitted: 19-Sep-2008 12:59:46
  • Last Modified: 23-Sep-2009 18:12:59
Revisions
  • Version: 2 public model Download this version
    • Submitted on: 23-Sep-2009 18:12:59
    • Submitted by: Bashar Ibrahim
    • With comment: Current version of Ibrahim2008_MCC_assembly_model_KDM
  • Version: 1 public model Download this version
    • Submitted on: 19-Sep-2008 12:59:46
    • Submitted by: Bashar Ibrahim
    • With comment: Original import of Kinetochore dependent MCC assembly model
Legends
: Variable used inside SBML models


Species
Species Initial Concentration/Amount
Mad1:C-Mad2

Mitotic spindle assembly checkpoint protein MAD2A ; Mitotic spindle assembly checkpoint protein MAD1 		5.0E-8 mol
O-Mad2

Mitotic spindle assembly checkpoint protein MAD2A 		1.3E-7 mol
Mad1:C-Mad2:O-Mad2*

Mitotic spindle assembly checkpoint protein MAD2A ; Mitotic spindle assembly checkpoint protein MAD1 		0.0 mol
Cdc20

Cell division cycle protein 20 homolog 		2.2E-7 mol
Cdc20:C-Mad2

Mitotic spindle assembly checkpoint protein MAD2A ; Cell division cycle protein 20 homolog 		0.0 mol
Bub3:BubR1

Mitotic checkpoint protein BUB3 ; Mitotic checkpoint serine/threonine-protein kinase BUB1 beta 		1.3E-7 mol
Reactions
Reactions Rate Parameters
(Mad1:C-Mad2 + O-Mad2) => (Mad1:C-Mad2:O-Mad2*)

([Mitotic spindle assembly checkpoint protein MAD2A; Mitotic spindle assembly checkpoint protein MAD1] + [Mitotic spindle assembly checkpoint protein MAD2A]) => ([Mitotic spindle assembly checkpoint protein MAD2A; Mitotic spindle assembly checkpoint protein MAD1])		 Cytoplasm*(u*k1f*Mad1_CMad2*OMad2-k1r*Mad1_CMad2_OMad2)

Cytoplasm*(u*k1f*[Mitotic spindle assembly checkpoint protein MAD2A; Mitotic spindle assembly checkpoint protein MAD1]*[Mitotic spindle assembly checkpoint protein MAD2A]-k1r*[Mitotic spindle assembly checkpoint protein MAD2A; Mitotic spindle assembly checkpoint protein MAD1])		 k1f = 200000.0 liter per mole per second; k1r = 0.2 per second; u = 1.0 dimensionless
(Mad1:C-Mad2:O-Mad2* + Cdc20) => (Mad1:C-Mad2 + Cdc20:C-Mad2)

([Mitotic spindle assembly checkpoint protein MAD2A; Mitotic spindle assembly checkpoint protein MAD1] + [Cell division cycle protein 20 homolog]) => ([Mitotic spindle assembly checkpoint protein MAD2A; Mitotic spindle assembly checkpoint protein MAD1] + [Mitotic spindle assembly checkpoint protein MAD2A; Cell division cycle protein 20 homolog])		 Cytoplasm*u*k2f*Mad1_CMad2_OMad2*Cdc20

Cytoplasm*u*k2f*[Mitotic spindle assembly checkpoint protein MAD2A; Mitotic spindle assembly checkpoint protein MAD1]*[Cell division cycle protein 20 homolog]		 k2f = 1.0E7 liter per mole per second; u = 1.0 dimensionless
(Cdc20:C-Mad2) => (Cdc20 + O-Mad2)

([Mitotic spindle assembly checkpoint protein MAD2A; Cell division cycle protein 20 homolog]) => ([Cell division cycle protein 20 homolog] + [Mitotic spindle assembly checkpoint protein MAD2A])		 Cytoplasm*k3f*Cdc20_CMad2

Cytoplasm*k3f*[Mitotic spindle assembly checkpoint protein MAD2A; Cell division cycle protein 20 homolog]		 k3f = 0.01 per second
(O-Mad2 + Cdc20) => (Cdc20:C-Mad2)

([Mitotic spindle assembly checkpoint protein MAD2A] + [Cell division cycle protein 20 homolog]) => ([Mitotic spindle assembly checkpoint protein MAD2A; Cell division cycle protein 20 homolog])		 Cytoplasm*kf6*OMad2*Cdc20

Cytoplasm*kf6*[Mitotic spindle assembly checkpoint protein MAD2A]*[Cell division cycle protein 20 homolog]		 kf6 = 1000.0 liter per mole per second
(Bub3:BubR1 + Cdc20) => (Bub3:BubR1:Cdc20)

([Mitotic checkpoint protein BUB3; Mitotic checkpoint serine/threonine-protein kinase BUB1 beta] + [Cell division cycle protein 20 homolog]) => ([Cell division cycle protein 20 homolog; Mitotic checkpoint serine/threonine-protein kinase BUB1 beta; Mitotic checkpoint protein BUB3])		 Cytoplasm*(u*k5f*Bub3_BubR1*Cdc20-k5r*Bub3_BubR1_Cdc20)

Cytoplasm*(u*k5f*[Mitotic checkpoint protein BUB3; Mitotic checkpoint serine/threonine-protein kinase BUB1 beta]*[Cell division cycle protein 20 homolog]-k5r*[Cell division cycle protein 20 homolog; Mitotic checkpoint serine/threonine-protein kinase BUB1 beta; Mitotic checkpoint protein BUB3])		 k5r = 0.2 per second; k5f = 10000.0 liter per mole per second; u = 1.0 dimensionless
(Cdc20:C-Mad2 + Bub3:BubR1) => (MCC)

([Mitotic spindle assembly checkpoint protein MAD2A; Cell division cycle protein 20 homolog] + [Mitotic checkpoint protein BUB3; Mitotic checkpoint serine/threonine-protein kinase BUB1 beta]) => ([mitotic checkpoint complex; Mitotic checkpoint serine/threonine-protein kinase BUB1 beta; Mitotic spindle assembly checkpoint protein MAD2A; Cell division cycle protein 20 homolog; Mitotic checkpoint protein BUB3])		 Cytoplasm*(u*k4f*Cdc20_CMad2*Bub3_BubR1-k4r*MCC)

Cytoplasm*(u*k4f*[Mitotic spindle assembly checkpoint protein MAD2A; Cell division cycle protein 20 homolog]*[Mitotic checkpoint protein BUB3; Mitotic checkpoint serine/threonine-protein kinase BUB1 beta]-k4r*[mitotic checkpoint complex; Mitotic checkpoint serine/threonine-protein kinase BUB1 beta; Mitotic spindle assembly checkpoint protein MAD2A; Cell division cycle protein 20 homolog; Mitotic checkpoint protein BUB3])		 k4r = 0.02 per second; u = 1.0 dimensionless; k4f = 1.0E7 liter per mole per second
Curator's comment:
(added: 19 Sep 2008, 12:59:19, updated: 19 Sep 2008, 12:59:19)
reproduction of fig. 2 b1,2 using SBML ODESolver 05072008 with options -n,-z,--error 1e-14 and --printstep 1e4