Smith2010 - Response of FOXO Transcription Factors to Post-Translational Modifications Made by Ageing-Related Signalling Pathways
Model Identifier
BIOMD0000000705
Short description
Format
SBML
(L2V4)
Related Publication
-
Modelling the response of FOXO transcription factors to multiple post-translational modifications made by ageing-related signalling pathways.
- Smith GR, Shanley DP
- PloS one , 6/ 2010 , Volume 5 , Issue 6 , pages: e11092 , PubMed ID: 20567500
- Henry Wellcome Laboratory for Biogerontology, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, UK.
- FOXO transcription factors are an important, conserved family of regulators of cellular processes including metabolism, cell-cycle progression, apoptosis and stress resistance. They are required for the efficacy of several of the genetic interventions that modulate lifespan. FOXO activity is regulated by multiple post-translational modifications (PTMs) that affect its subcellular localization, half-life, DNA binding and transcriptional activity. Here, we show how a mathematical modelling approach can be used to simulate the effects, singly and in combination, of these PTMs. Our model is implemented using the Systems Biology Markup Language (SBML), generated by an ancillary program and simulated in a stochastic framework. The use of the ancillary program to generate the SBML is necessary because the possibility that many regulatory PTMs may be added, each independently of the others, means that a large number of chemically distinct forms of the FOXO molecule must be taken into account, and the program is used to generate them. Although the model does not yet include detailed representations of events upstream and downstream of FOXO, we show how it can qualitatively, and in some cases quantitatively, reproduce the known effects of certain treatments that induce various single and multiple PTMs, and allows for a complex spatiotemporal interplay of effects due to the activation of multiple PTM-inducing treatments. Thus, it provides an important framework to integrate current knowledge about the behaviour of FOXO. The approach should be generally applicable to other proteins experiencing multiple regulations.
Contributors
Submitter of the first revision: Ishan Ajmera
Submitter of this revision: administrator
Modellers: administrator, Ishan Ajmera
Submitter of this revision: administrator
Modellers: administrator, Ishan Ajmera
Metadata information
is (2 statements)
isDescribedBy (2 statements)
hasTaxon (1 statement)
hasProperty (1 statement)
hasPart (4 statements)
isDescribedBy (2 statements)
hasTaxon (1 statement)
hasProperty (1 statement)
hasPart (4 statements)
NCIt
Apoptosis
Gene Ontology regulation of cell cycle
Gene Ontology metabolic process
Gene Ontology post-translational protein modification
Gene Ontology regulation of cell cycle
Gene Ontology metabolic process
Gene Ontology post-translational protein modification
Curation status
Curated
Modelling approach(es)
Tags
Connected external resources
SBGN view in Newt Editor
| Name | Description | Size | Actions |
|---|---|---|---|
Model files |
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| BIOMD0000000705_url.xml | SBML L2V4 representation of Smith2010 - Response of FOXO Transcription Factors to Post-Translational Modifications Made by Ageing-Related Signalling Pathways | 281.30 KB | Preview | Download |
Additional files |
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| BIOMD0000000705-biopax2.owl | Auto-generated BioPAX (Level 2) | 84.79 KB | Preview | Download |
| BIOMD0000000705-biopax3.owl | Auto-generated BioPAX (Level 3) | 143.86 KB | Preview | Download |
| BIOMD0000000705.m | Auto-generated Octave file | 38.11 KB | Preview | Download |
| BIOMD0000000705.png | Auto-generated Reaction graph (PNG) | 963.55 KB | Preview | Download |
| BIOMD0000000705.sci | Auto-generated Scilab file | 154.00 Bytes | Preview | Download |
| BIOMD0000000705.svg | Auto-generated Reaction graph (SVG) | 146.07 KB | Preview | Download |
| BIOMD0000000705.vcml | Auto-generated VCML file | 897.00 Bytes | Preview | Download |
| BIOMD0000000705.xpp | Auto-generated XPP file | 35.70 KB | Preview | Download |
| BIOMD0000000705_urn.xml | Auto-generated SBML file with URNs | 281.27 KB | Preview | Download |
| Smith2010_figure_4C_blue_curve.cps | Copasi file for reproducing figure 4 (blue curve) in the reference publication. | 314.25 KB | Preview | Download |
| Smith2010_figure_4C_blue_curve.sedml | SED-ML file to reproduce Figure 4 (blue curve) in the reference publication | 1.77 KB | Preview | Download |
| Smith2010_figure_4C_red_curve.cps | Copasi file for reproducing figure 4 (red curve) in the reference publication. | 314.24 KB | Preview | Download |
| Smith2010_figure_4C_red_curve.sedml | SED-ML file to reproduce Figure 4 (red curve) in the reference publication | 1.77 KB | Preview | Download |
- Model originally submitted by : Ishan Ajmera
- Submitted: Dec 26, 2011 11:52:44 PM
- Last Modified: May 31, 2018 6:28:54 PM
Revisions
-
Version: 3
- Submitted on: May 31, 2018 6:28:54 PM
- Submitted by: administrator
- With comment: Annotated file model of the reference publication with explicit names of species and reactions
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Version: 2
- Submitted on: Dec 30, 2011 12:07:20 AM
- Submitted by: Ishan Ajmera
- With comment: Current version of Smith2010_Foxo_PTMs_AgeingRelatedSignallingPathway_A
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Version: 1
- Submitted on: Dec 26, 2011 11:52:44 PM
- Submitted by: Ishan Ajmera
- With comment: Original import of Smith2010_Foxo_PTMs_AgeingRelatedSignallingPathway_A
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Legends
: Variable used inside SBML models
: Variable used inside SBML models
Species
| Species | Initial Concentration/Amount |
|---|---|
| degr Foxo1 Forkhead box protein O1 ; Removed |
0.0 item |
| cytoplasm Foxo1 Pa0 pUb1 Forkhead box protein O1 ; ubiquitinated protein |
0.0 item |
| dnabound Foxo1 Pa1 pUb0 Forkhead box protein O1 ; phosphorylated |
0.0 item |
| nucleus RNA Inr ribonucleic acid |
0.0 item |
| Foxo1 total rate | 1.0 item |
| cytoplasm Foxo1 Pa1 pUb0 Forkhead box protein O1 ; phosphorylated |
0.0 item |
| dnabound Foxo1 tot Forkhead box protein O1 |
0.0 item |
| cytoplasm Foxo1 Pa0 pUb0 Forkhead box protein O1 |
6.06060606060606E13 item |
Reactions
| Reactions | Rate | Parameters |
|---|---|---|
| cytoplasm_Foxo1_Pa1_pUb1 => degr_Foxo1; Proteasome | cytoplasm*cytoplasm_Foxo1_Pa1_pUb1*cytoplasm*Proteasome*cytoplasm*kdeg/cytoplasm | kdeg = 1.0E-4 |
| nucleus_Foxo1_Pa0_pUb1 => cytoplasm_Foxo1_Pa0_pUb1 | nucleus_Foxo1_Pa0_pUb1*nucleus*ktr4_055 | ktr4_055 = 0.055 |
| dnabound_Foxo1_Pa1_pUb0 => dnabound_Foxo1_Pa1_pUb1; SCF | dnabound_Foxo1_Pa1_pUb0*dnabound*SCF*cytoplasm*kub2 | kub2 = 3.0E-6 |
| null => nucleus_RNA_Inr | transcription_rate | transcription_rate = 3.0 |
| Foxo1_total_rate = Foxo1_all/Metabolite_21 | [] | Metabolite_21 = 1.20481927710843E14 |
| cytoplasm_Foxo1_Pa0_pUb1 => nucleus_Foxo1_Pa0_pUb1 | cytoplasm_Foxo1_Pa0_pUb1*cytoplasm*ktr1_181818 | ktr1_181818 = 0.181818 |
| cytoplasm_Foxo1_Pa1_pUb0 => cytoplasm_Foxo1_Pa0_pUb0; PP2A | cytoplasm*cytoplasm_Foxo1_Pa1_pUb0*cytoplasm*PP2A*cytoplasm*kdephos/cytoplasm | kdephos = 5.0E-5 |
| dnabound_Foxo1_tot = (dnabound_Foxo1_Pa0_pUb0*dnabound+dnabound_Foxo1_Pa0_pUb1*dnabound+dnabound_Foxo1_Pa1_pUb0*dnabound+dnabound_Foxo1_Pa1_pUb1*dnabound)/extracellular | [] | [] |
| nucleus_Foxo1_Pa0_pUb0 => cytoplasm_Foxo1_Pa0_pUb0 | nucleus_Foxo1_Pa0_pUb0*nucleus*ktr4_055 | ktr4_055 = 0.055 |
| cytoplasm_Foxo1_Pa0_pUb1 => cytoplasm_Foxo1_Pa1_pUb1; Akt | cytoplasm*cytoplasm_Foxo1_Pa0_pUb1*cytoplasm*Akt*cytoplasm*kkin/cytoplasm | kkin = 5.0E-5 |
Curator's comment:
(added: 31 May 2018, 18:28:29, updated: 31 May 2018, 18:28:29)
(added: 31 May 2018, 18:28:29, updated: 31 May 2018, 18:28:29)
Figure 4 of the reference publication (blue curve) has been reproduced using Copasi 4.23 (Build 184)