Ibrahim2008_MCC_assembly_model_KDM

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.
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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.
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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.
Metadata information
Name | Description | Size | Actions |
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Model files |
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BIOMD0000000193_url.xml | SBML L2V3 representation of Ibrahim2008_MCC_assembly_model_KDM | 23.97 KB | Preview | Download |
Additional files |
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BIOMD0000000193-biopax2.owl | Auto-generated BioPAX (Level 2) | 17.54 KB | Preview | Download |
BIOMD0000000193.xpp | Auto-generated XPP file | 3.15 KB | Preview | Download |
BIOMD0000000193.png | Auto-generated Reaction graph (PNG) | 48.81 KB | Preview | Download |
BIOMD0000000193_urn.xml | Auto-generated SBML file with URNs | 26.16 KB | Preview | Download |
BIOMD0000000193.vcml | Auto-generated VCML file | 36.48 KB | Preview | Download |
BIOMD0000000193.pdf | Auto-generated PDF file | 186.78 KB | Preview | Download |
BIOMD0000000193.svg | Auto-generated Reaction graph (SVG) | 18.03 KB | Preview | Download |
BIOMD0000000193.m | Auto-generated Octave file | 4.99 KB | Preview | Download |
BIOMD0000000193-biopax3.owl | Auto-generated BioPAX (Level 3) | 25.76 KB | Preview | Download |
BIOMD0000000193.sci | Auto-generated Scilab file | 67.00 Bytes | Preview | Download |
- Model originally submitted by : Bashar Ibrahim
- Submitted: 19-Sep-2008 12:59:46
- Last Modified: 23-Sep-2009 18:12:59
Revisions
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Version: 2
- Submitted on: 23-Sep-2009 18:12:59
- Submitted by: Bashar Ibrahim
- With comment: Current version of Ibrahim2008_MCC_assembly_model_KDM
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Version: 1
- Submitted on: 19-Sep-2008 12:59:46
- Submitted by: Bashar Ibrahim
- With comment: Original import of Kinetochore dependent MCC assembly model
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revisions as only public revisions are displayed here. Any private revisions
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: Variable used inside SBML models
Species | Initial Concentration/Amount |
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Cdc20 CMad2 Mitotic spindle assembly checkpoint protein MAD2A ; Cell division cycle protein 20 homolog |
0.0 mol |
MCC 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 |
0.0 mol |
Bub3 BubR1 Cdc20 Cell division cycle protein 20 homolog ; Mitotic checkpoint serine/threonine-protein kinase BUB1 beta ; Mitotic checkpoint protein BUB3 |
0.0 mol |
OMad2 Mitotic spindle assembly checkpoint protein MAD2A |
1.3E-7 mol |
Mad1 CMad2 OMad2 Mitotic spindle assembly checkpoint protein MAD2A ; Mitotic spindle assembly checkpoint protein MAD1 |
0.0 mol |
Bub3 BubR1 Mitotic checkpoint protein BUB3 ; Mitotic checkpoint serine/threonine-protein kinase BUB1 beta |
1.3E-7 mol |
Mad1 CMad2 Mitotic spindle assembly checkpoint protein MAD2A ; Mitotic spindle assembly checkpoint protein MAD1 |
5.0E-8 mol |
Reactions | Rate | Parameters |
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OMad2 + Cdc20 => Cdc20_CMad2 | Cytoplasm*kf6*OMad2*Cdc20 | kf6 = 1000.0 liter per mole per second |
Cdc20_CMad2 + Bub3_BubR1 => MCC | Cytoplasm*(u*k4f*Cdc20_CMad2*Bub3_BubR1-k4r*MCC) | k4r = 0.02 per second; u = 1.0 dimensionless; k4f = 1.0E7 liter per mole per second |
Bub3_BubR1 + Cdc20 => Bub3_BubR1_Cdc20 | Cytoplasm*(u*k5f*Bub3_BubR1*Cdc20-k5r*Bub3_BubR1_Cdc20) | k5r = 0.2 per second; k5f = 10000.0 liter per mole per second; u = 1.0 dimensionless |
Mad1_CMad2 + OMad2 => Mad1_CMad2_OMad2 | Cytoplasm*(u*k1f*Mad1_CMad2*OMad2-k1r*Mad1_CMad2_OMad2) | k1f = 200000.0 liter per mole per second; k1r = 0.2 per second; u = 1.0 dimensionless |
Mad1_CMad2_OMad2 + Cdc20 => Mad1_CMad2 + Cdc20_CMad2 | Cytoplasm*u*k2f*Mad1_CMad2_OMad2*Cdc20 | k2f = 1.0E7 liter per mole per second; u = 1.0 dimensionless |
Cdc20_CMad2 => Cdc20 + OMad2 | Cytoplasm*k3f*Cdc20_CMad2 | k3f = 0.01 per second |
(added: 19 Sep 2008, 12:59:19, updated: 19 Sep 2008, 12:59:19)