Caydasi2012 - Regulation of Tem1 by the GAP complex in spindle position cell cycle checkpoint - Ubiquitous association model
This model is described in the article:
Abstract:
The orientation of the mitotic spindle with respect to the polarity axis is crucial for the accuracy of asymmetric cell division. In budding yeast, a surveillance mechanism called the spindle position checkpoint (SPOC) prevents exit from mitosis when the mitotic spindle fails to align along the mother-to-daughter polarity axis. SPOC arrest relies upon inhibition of the GTPase Tem1 by the GTPase-activating protein (GAP) complex Bfa1-Bub2. Importantly, reactions signaling mitotic exit take place at yeast centrosomes (named spindle pole bodies, SPBs) and the GAP complex also promotes SPB localization of Tem1. Yet, whether the regulation of Tem1 by Bfa1-Bub2 takes place only at the SPBs remains elusive. Here, we present a quantitative analysis of Bfa1-Bub2 and Tem1 localization at the SPBs. Based on the measured SPB-bound protein levels, we introduce a dynamical model of the SPOC that describes the regulation of Bfa1 and Tem1. Our model suggests that Bfa1 interacts with Tem1 in the cytoplasm as well as at the SPBs to provide efficient Tem1 inhibition.
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To cite BioModels Database, please use: Chelliah V et al. BioModels: ten-year anniversary. Nucl. Acids Res. 2015, 43(Database issue):D542-8.
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A dynamical model of the spindle position checkpoint.
- Caydasi AK, Lohel M, Grünert G, Dittrich P, Pereira G, Ibrahim B
- Molecular Systems Biology , 1/ 2012 , Volume 8 , pages: 582 , PubMed ID: 22580890
- Molecular Biology of Centrosomes and Cilia, German Cancer Research Center, DKFZ-ZMBH Alliance, Heidelberg, Germany.
- The orientation of the mitotic spindle with respect to the polarity axis is crucial for the accuracy of asymmetric cell division. In budding yeast, a surveillance mechanism called the spindle position checkpoint (SPOC) prevents exit from mitosis when the mitotic spindle fails to align along the mother-to-daughter polarity axis. SPOC arrest relies upon inhibition of the GTPase Tem1 by the GTPase-activating protein (GAP) complex Bfa1-Bub2. Importantly, reactions signaling mitotic exit take place at yeast centrosomes (named spindle pole bodies, SPBs) and the GAP complex also promotes SPB localization of Tem1. Yet, whether the regulation of Tem1 by Bfa1-Bub2 takes place only at the SPBs remains elusive. Here, we present a quantitative analysis of Bfa1-Bub2 and Tem1 localization at the SPBs. Based on the measured SPB-bound protein levels, we introduce a dynamical model of the SPOC that describes the regulation of Bfa1 and Tem1. Our model suggests that Bfa1 interacts with Tem1 in the cytoplasm as well as at the SPBs to provide efficient Tem1 inhibition.
Submitter of this revision: Rahuman Sheriff
Modellers: Rahuman Sheriff, Bashar Ibrahim
Metadata information
isDescribedBy (2 statements)
hasTaxon (1 statement)
hasProperty (4 statements)
Gene Ontology mitotic spindle orientation checkpoint
Gene Ontology mitotic spindle organization
Mathematical Modelling Ontology Ordinary differential equation model
Connected external resources
SBGN view in Newt Editor
| Name | Description | Size | Actions |
|---|---|---|---|
Model files |
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| BIOMD0000000699_url.xml | SBML L2V4 representation of Caydasi2012 - Regulation of Tem1 by the GAP complex in spindle position cell cycle checkpoint - Ubiquitous association model | 261.44 KB | Preview | Download |
Additional files |
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| BIOMD0000000699-biopax3.owl | Auto-generated BioPAX (Level 3) | 122.21 KB | Preview | Download |
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| BIOMD0000000699.sci | Auto-generated Scilab file | 67.00 Bytes | Preview | Download |
| BIOMD0000000699.svg | Auto-generated Reaction graph (SVG) | 97.46 KB | Preview | Download |
| BIOMD0000000699.vcml | Auto-generated VCML file | 897.00 Bytes | Preview | Download |
| BIOMD0000000699.xpp | Auto-generated XPP file | 24.51 KB | Preview | Download |
| BIOMD0000000699_urn.xml | Auto-generated SBML file with URNs | 261.27 KB | Preview | Download |
| MODEL1202090002_Fig5 i.sedml | SEDML file to reproduce Figure 5 i in the reference publication | 6.78 KB | Preview | Download |
| MODEL1202090002_Figure5_i.cps | Copasi file for reproducing figure 5 I in the reference publication. | 312.51 KB | Preview | Download |
- Model originally submitted by : Bashar Ibrahim
- Submitted: Feb 9, 2012 7:14:06 PM
- Last Modified: May 21, 2018 3:49:22 PM
Revisions
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Version: 3
- Submitted on: May 21, 2018 3:49:22 PM
- Submitted by: Rahuman Sheriff
- With comment: Notes updated using online editor.
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Version: 2
- Submitted on: May 10, 2012 2:50:01 PM
- Submitted by: Bashar Ibrahim
- With comment: Current version of Caydasi2012_SPOC_UbiquitousAssociation
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Version: 1
- Submitted on: Feb 9, 2012 7:14:06 PM
- Submitted by: Bashar Ibrahim
- With comment: Original import of MODEL1202090002.xml.origin
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: Variable used inside SBML models
| Species | Initial Concentration/Amount |
|---|---|
| Bfa1P5 Mitotic check point protein BFA1 ; increased phosphorylation |
0.0 mol |
| Tem1GDP GDP ; Protein TEM1 |
7.99E-9 mol |
| B Bfa1P4 Mitotic check point protein BFA1 ; binding site ; phosphorylated |
0.0 mol |
| B Bfa1 Tem1GTP GTP ; binding site ; Protein TEM1 ; Mitotic check point protein BFA1 |
0.0 mol |
| Bfa1 Tem1GDP Protein TEM1 ; GDP ; Mitotic check point protein BFA1 |
0.0 mol |
| Inactive Tem1 in the cytosol Protein TEM1 ; inactive |
481.16910585 mol |
| Bfa1P4 Mitotic check point protein BFA1 ; phosphorylated |
0.0 mol |
| Reactions | Rate | Parameters |
|---|---|---|
| Bfa1P5 + SPB_B => B_Bfa1P5 | c3*(konB*SPB_B*Bfa1P5-koffB*B_Bfa1P5) | konB = 1250000.0 l/(mol*s); koffB = 0.0012 1/s |
| Bfa1P5 + Tem1GDP => Bfa1P5_Tem1GDP | c2*(alpha*konB5T*Bfa1P5*Tem1GDP-koffBT*Bfa1P5_Tem1GDP) | alpha = 1.0 1; koffBT = 0.183 1/s; konB5T = 7000000.0 l/(mol*s) |
| Bfa1P4 + Tem1GDP => Bfa1P4_Tem1GDP | c2*(alpha*konB4T*Bfa1P4*Tem1GDP-koffBT*Bfa1P4_Tem1GDP) | konB4T = 3.65E7 l/(mol*s); alpha = 1.0 1; koffBT = 0.183 1/s |
| Bfa1P4 + SPB_B => B_Bfa1P4 | c3*(konB4*SPB_B*Bfa1P4-koffB4*B_Bfa1P4) | koffB4 = 0.0365 1/s; konB4 = 20000.0 l/(mol*s) |
| B_Bfa1_Tem1GTP => B_Bfa1_Tem1GDP | c3*khydBT*B_Bfa1_Tem1GTP | khydBT = 2.0 1/s |
| Bfa1 + Tem1GDP => Bfa1_Tem1GDP | c2*(alpha*konBT*Bfa1*Tem1GDP-koffBT*Bfa1_Tem1GDP) | alpha = 1.0 1; koffBT = 0.183 1/s; konBT = 3.65E7 l/(mol*s) |
| Bfa1_Tem1GDP => Bfa1P4_Tem1GDP | c2*u*kfKin4Cyto*Bfa1_Tem1GDP | kfKin4Cyto = 0.09 1/s; u = 1.0 1 |
| Inactive_Tem1_in_the_cytosol = (Tem1GDP+Bfa1_Tem1GDP+Bfa1P4_Tem1GDP+Bfa1P5_Tem1GDP)*c2*avogadro | [] | avogadro = 6.0221415E23 |
| Bfa1P4 => Bfa1 | c2*krKin4*Bfa1P4 | krKin4 = 0.0251 1/s |
(added: 11 May 2018, 18:15:49, updated: 11 May 2018, 18:15:49)