Ciliberto2003 - CyclinE / Cdk2 timer in the cell cycle of Xenopus laevis embryo
This model is described in the article:
Abstract:
Early cell cycles of Xenopus laevis embryos are characterized by rapid oscillations in the activity of two cyclin-dependent kinases. Cdk1 activity peaks at mitosis, driven by periodic degradation of cyclins A and B. In contrast, Cdk2 activity oscillates twice per cell cycle, despite a constant level of its partner, cyclin E. Cyclin E degrades at a fixed time after fertilization, normally corresponding to the midblastula transition. Based on published data and new experiments, we constructed a mathematical model in which: (1) oscillations in Cdk2 activity depend upon changes in phosphorylation, (2) Cdk2 participates in a negative feedback loop with the inhibitory kinase Wee1; (3) cyclin E is cooperatively removed from the oscillatory system; and (4) removed cyclin E is degraded by a pathway activated by cyclin E/Cdk2 itself. The model's predictions about embryos injected with Xic1, a stoichiometric inhibitor of cyclin E/Cdk2, were experimentally validated.
This model is hosted on BioModels Database and identified by: BIOMD0000000697.
To cite BioModels Database, please use: Chelliah V et al. BioModels: ten-year anniversary. Nucl. Acids Res. 2015, 43(Database issue):D542-8.
To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.
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A kinetic model of the cyclin E/Cdk2 developmental timer in Xenopus laevis embryos.
- Ciliberto A, Petrus MJ, Tyson JJ, Sible JC
- Biophysical chemistry , 7/ 2003 , Volume 104 , Issue 3 , pages: 573-589 , PubMed ID: 12914904
- Biology Department, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061-0406, USA. ancilibe@vt.edu
- Early cell cycles of Xenopus laevis embryos are characterized by rapid oscillations in the activity of two cyclin-dependent kinases. Cdk1 activity peaks at mitosis, driven by periodic degradation of cyclins A and B. In contrast, Cdk2 activity oscillates twice per cell cycle, despite a constant level of its partner, cyclin E. Cyclin E degrades at a fixed time after fertilization, normally corresponding to the midblastula transition. Based on published data and new experiments, we constructed a mathematical model in which: (1) oscillations in Cdk2 activity depend upon changes in phosphorylation, (2) Cdk2 participates in a negative feedback loop with the inhibitory kinase Wee1; (3) cyclin E is cooperatively removed from the oscillatory system; and (4) removed cyclin E is degraded by a pathway activated by cyclin E/Cdk2 itself. The model's predictions about embryos injected with Xic1, a stoichiometric inhibitor of cyclin E/Cdk2, were experimentally validated.
Submitter of this revision: Rahuman Sheriff
Modellers: Vijayalakshmi Chelliah, Rahuman Sheriff
Metadata information
isDescribedBy (1 statement)
hasPart (1 statement)
hasProperty (1 statement)
occursIn (1 statement)
hasTaxon (1 statement)
Connected external resources
SBGN view in Newt Editor
| Name | Description | Size | Actions |
|---|---|---|---|
Model files |
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| BIOMD0000000697_url.xml | SBML L2V4 representation of Ciliberto2003 - CyclinE / Cdk2 timer in the cell cycle of Xenopus laevis embryo | 136.91 KB | Preview | Download |
Additional files |
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| BIOMD0000000697-biopax2.owl | Auto-generated BioPAX (Level 2) | 44.32 KB | Preview | Download |
| BIOMD0000000697-biopax3.owl | Auto-generated BioPAX (Level 3) | 75.55 KB | Preview | Download |
| BIOMD0000000697.m | Auto-generated Octave file | 15.83 KB | Preview | Download |
| BIOMD0000000697.pdf | Auto-generated PDF file | 234.33 KB | Preview | Download |
| BIOMD0000000697.png | Auto-generated Reaction graph (PNG) | 310.13 KB | Preview | Download |
| BIOMD0000000697.sci | Auto-generated Scilab file | 170.00 Bytes | Preview | Download |
| BIOMD0000000697.svg | Auto-generated Reaction graph (SVG) | 74.38 KB | Preview | Download |
| BIOMD0000000697.vcml | Auto-generated VCML file | 953.00 Bytes | Preview | Download |
| BIOMD0000000697.xpp | Auto-generated XPP file | 12.12 KB | Preview | Download |
| BIOMD0000000697_urn.xml | Auto-generated SBML file with URNs | 136.55 KB | Preview | Download |
| MODEL0913242281_fig5.sedml | SEDML file to generate Figure 5a and 5b | 5.11 KB | Preview | Download |
| MODEL0913242281_fig6.sedml | SEDML file to generate Figure 6a, 6b and 6c | 6.27 KB | Preview | Download |
| MODEL0913242281_final.cps | Model is implemented in the attached COPASI file. The parameters are set to generate Figure 5. | 149.33 KB | Preview | Download |
- Model originally submitted by : Vijayalakshmi Chelliah
- Submitted: Apr 30, 2009 1:00:15 PM
- Last Modified: May 1, 2018 1:26:48 PM
Revisions
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Version: 3
- Submitted on: May 1, 2018 1:26:48 PM
- Submitted by: Rahuman Sheriff
- With comment: Notes updated using online editor.
-
Version: 2
- Submitted on: Apr 30, 2009 1:00:15 PM
- Submitted by: Vijayalakshmi Chelliah
- With comment: Current version of Ciliberto2003_CyclinECdk2Timer
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Version: 1
- Submitted on: Apr 30, 2009 1:00:15 PM
- Submitted by: Vijayalakshmi Chelliah
- With comment: Original import of Ciliberto2003_CyclinECdk2Timer
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: Variable used inside SBML models
| Species | Initial Concentration/Amount |
|---|---|
| Xic NP 001108275.1 |
2.99999999999998 mmol |
| Xic Cdk2 CycE G1/S-specific cyclin-E1 ; protein-containing complex ; Cyclin-dependent kinase 2 ; NP 001108275.1 |
0.0 mmol |
| Xic PCdk2 CycErem Cyclin-dependent kinase 2 ; protein-containing complex ; phosphorylated ; G1/S-specific cyclin-E1 ; inactive ; NP 001108275.1 |
0.0 mmol |
| Cyc total G1/S-specific cyclin-E1 |
1.0 mmol |
| Cdk2 CycE G1/S-specific cyclin-E1 ; cyclin E1-CDK2 complex ; Cyclin-dependent kinase 2 |
0.0599999999999999 mmol |
| Cdk2 CycErem Cyclin-dependent kinase 2 ; cyclin E1-CDK2 complex ; inactive ; G1/S-specific cyclin-E1 |
0.0 mmol |
| PCdk2 CycErem G1/S-specific cyclin-E1 ; cyclin E1-CDK2 complex ; inactive ; Cyclin-dependent kinase 2 ; phosphorylated |
0.0 mmol |
| Reactions | Rate | Parameters |
|---|---|---|
| Xic + Cdk2_CycE => Xic_Cdk2_CycE | compartment*kassoc*Xic*Cdk2_CycE | kassoc = 0.1 1/s |
| Xic_PCdk2_CycE => Xic_Cdk2_CycE | compartment*k25A*Xic_PCdk2_CycE | k25A = 0.1 1/s |
| Xic_Cdk2_CycE => Xic_Cdk2_CycErem | compartment*kon*phi*Xic_Cdk2_CycE | kon = 0.02 1/s; phi = 0.0390625 1 |
| Xic + PCdk2_CycErem => Xic_PCdk2_CycErem | compartment*kassoc*Xic*PCdk2_CycErem | kassoc = 0.1 1/s |
| Cyc_total = Xic_PCdk2_CycE+Xic_Cdk2_CycE+Xic_PCdk2_CycErem+Xic_Cdk2_CycErem+PCdk2_CycErem+Cdk2_CycErem+Cdk2_CycE+PCdk2_CycE | [] | [] |
| Cdk2_CycErem => Cdk2_CycE | compartment*koff*Cdk2_CycErem | koff = 1.0E-4 1/s |
| Cdk2_CycE => Cdk2_CycErem | compartment*kon*phi*Cdk2_CycE | kon = 0.02 1/s; phi = 0.0390625 1 |
| PCdk2_CycE => Cdk2_CycE | compartment*k25A*PCdk2_CycE | k25A = 0.1 1/s |
| Xic + Cdk2_CycErem => Xic_Cdk2_CycErem | compartment*kassoc*Xic*Cdk2_CycErem | kassoc = 0.1 1/s |
| PCdk2_CycE => PCdk2_CycErem | compartment*kon*phi*PCdk2_CycE | kon = 0.02 1/s; phi = 0.0390625 1 |
(added: 01 May 2018, 12:51:55, updated: 01 May 2018, 12:51:55)