Smith2010 - Response of FOXO Transcription Factors to Post-Translational Modifications (with acetylation pathway)

  public model
Model Identifier
BIOMD0000000706
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

Metadata information

is (2 statements)
BioModels Database MODEL1112260001
BioModels Database BIOMD0000000706

isDescribedBy (2 statements)
hasTaxon (1 statement)
Taxonomy Eukaryota

hasPart (1 statement)
hasProperty (1 statement)
Mathematical Modelling Ontology Ordinary differential equation model

Curation status
Curated
Modelling approach(es)
ordinary differential equation model
Tags

Connected external resources

SBGN view in Newt Editor

Name Description Size Actions

Model files
BIOMD0000000706_url.xml SBML L2V4 representation of Smith2010 - Response of FOXO Transcription Factors to Post-Translational Modifications (with acetylation pathway) 555.52 KB Preview | Download

Additional files
BIOMD0000000706-biopax2.owl Auto-generated BioPAX (Level 2) 159.22 KB Preview | Download
BIOMD0000000706-biopax3.owl Auto-generated BioPAX (Level 3) 286.65 KB Preview | Download
BIOMD0000000706.m Auto-generated Octave file 88.04 KB Preview | Download
BIOMD0000000706.png Auto-generated Reaction graph (PNG) 3.63 MB Preview | Download
BIOMD0000000706.sci Auto-generated Scilab file 67.00 Bytes Preview | Download
BIOMD0000000706.svg Auto-generated Reaction graph (SVG) 313.55 KB Preview | Download
BIOMD0000000706.vcml Auto-generated VCML file 897.00 Bytes Preview | Download
BIOMD0000000706.xpp Auto-generated XPP file 83.52 KB Preview | Download
BIOMD0000000706_urn.xml Auto-generated SBML file with URNs 555.50 KB Preview | Download
Smith2010_figure_4D_blue_curve.cps Copasi file for reproducing figure 4D (blue curve) in the reference publication. (Copasi 4.23 Build 184) 575.04 KB Preview | Download
Smith2010_figure_4D_blue_curve.sedml SEDML file to reproduce Figure 4D (blue curve) i in the reference publication 1.74 KB Preview | Download
Smith2010_figure_4D_red_curve.cps Copasi file for reproducing figure 4D (red curve) in the reference publication. (Copasi 4.23 Build 184) 466.96 KB Preview | Download
Smith2010_figure_4D_red_curve.sedml SEDML file to reproduce Figure 4D (red curve) i in the reference publication 1.74 KB Preview | Download

  • Model originally submitted by : Ishan Ajmera
  • Submitted: Dec 26, 2011 11:53:05 PM
  • Last Modified: Jun 1, 2018 1:14:20 PM
Revisions
  • Version: 3 public model Download this version
    • Submitted on: Jun 1, 2018 1:14:20 PM
    • Submitted by: administrator
    • With comment: Annotated file model of the reference publication with explicit names of species and reactions
  • Version: 2 public model Download this version
    • Submitted on: Dec 30, 2011 12:09:21 AM
    • Submitted by: Ishan Ajmera
    • With comment: Current version of Smith2010_Foxo_PTMs_AgeingRelatedSignallingPathway_B
  • Version: 1 public model Download this version
    • Submitted on: Dec 26, 2011 11:53:05 PM
    • Submitted by: Ishan Ajmera
    • With comment: Original import of Smith2010_Foxo_PTMs_AgeingRelatedSignallingPathway_B

(*) You might be seeing discontinuous revisions as only public revisions are displayed here. Any private revisions unpublished model revision of this model will only be shown to the submitter and their collaborators.

Legends
: Variable used inside SBML models


Species
Species Initial Concentration/Amount
nucleus Foxo1 Pa0 Ac1 pUb0

Forkhead box protein O1 ; acetylated protein 		0.0 item
cytoplasm Foxo1 Pa1 Ac1 pUb1

Forkhead box protein O1 ; ubiquitinated protein ; phosphorylated ; acetylated protein 		0.0 item
nucleus Foxo1 Pa1 Ac1 pUb1

Forkhead box protein O1 ; ubiquitinated protein ; acetylated protein ; phosphorylated 		0.0 item
dnabound Foxo1 Pa1 Ac1 pUb1

Forkhead box protein O1 ; phosphorylated ; ubiquitinated protein ; acetylated protein 		0.0 item
cytoplasm Foxo1 tot

Forkhead box protein O1 		1.20481927710843E14 item
nucleus RNA Inr 0.0 item
nucleus RNA Sod2 0.0 item
dnabound Foxo1 Pa0 Ac0 pUb1

Forkhead box protein O1 ; ubiquitinated protein 		0.0 item
dnabound Foxo1 Pa0 Ac1 pUb1

Forkhead box protein O1 ; ubiquitinated protein ; acetylated protein 		0.0 item
Reactions
Reactions Rate Parameters
nucleus_Foxo1_Pa0_Ac0_pUb0 => nucleus_Foxo1_Pa0_Ac1_pUb0; CBPP300 nucleus_Foxo1_Pa0_Ac0_pUb0*nucleus*CBPP300*cytoplasm*kacet kacet=1.0E-4
nucleus_Foxo1_Pa1_Ac1_pUb1 => cytoplasm_Foxo1_Pa1_Ac1_pUb1 nucleus_Foxo1_Pa1_Ac1_pUb1*nucleus*ktr ktr=0.55
cytoplasm_Foxo1_Pa1_Ac1_pUb0 => cytoplasm_Foxo1_Pa1_Ac1_pUb1; SCF cytoplasm*cytoplasm_Foxo1_Pa1_Ac1_pUb0*cytoplasm*SCF*cytoplasm*kub/cytoplasm kub=1.0E-7
nucleus_Foxo1_Pa1_Ac1_pUb1 => nucleus_Foxo1_Pa1_Ac0_pUb1; SIRT1 nucleus_Foxo1_Pa1_Ac1_pUb1*nucleus*SIRT1*cytoplasm*kdeac kdeac=1.0E-4
dnabound_Foxo1_Pa0_Ac1_pUb1 => dnabound_Foxo1_Pa1_Ac1_pUb1; Akt dnabound_Foxo1_Pa0_Ac1_pUb1*dnabound*Akt*cytoplasm*kkin kkin=5.0E-5
cytoplasm_Foxo1_tot = (cytoplasm_Foxo1_Pa0_Ac0_pUb0*cytoplasm+cytoplasm_Foxo1_Pa0_Ac0_pUb1*cytoplasm+cytoplasm_Foxo1_Pa0_Ac1_pUb0*cytoplasm+cytoplasm_Foxo1_Pa0_Ac1_pUb1*cytoplasm+cytoplasm_Foxo1_Pa1_Ac0_pUb0*cytoplasm+cytoplasm_Foxo1_Pa1_Ac0_pUb1*cytoplasm+cytoplasm_Foxo1_Pa1_Ac1_pUb0*cytoplasm+cytoplasm_Foxo1_Pa1_Ac1_pUb1*cytoplasm)/extracellular [] []
null => nucleus_RNA_Inr; dnabound_Foxo1_Pa1_Ac0_pUb1 dnabound_Foxo1_Pa1_Ac0_pUb1*dnabound*ktranscr ktranscr=0.3
null => nucleus_RNA_Sod2 v v=3.0
nucleus_Foxo1_Pa0_Ac0_pUb1 => dnabound_Foxo1_Pa0_Ac0_pUb1 nucleus_Foxo1_Pa0_Ac0_pUb1*nucleus*ktr ktr=0.25
nucleus_Foxo1_Pa0_Ac1_pUb1 => dnabound_Foxo1_Pa0_Ac1_pUb1 nucleus_Foxo1_Pa0_Ac1_pUb1*nucleus*ktr ktr=0.125
Curator's comment:
(added: 01 Jun 2018, 13:13:51, updated: 01 Jun 2018, 13:13:51)
Figure 4D (blue curve) of the reference publication has been reproduced using Copasi 4.23 (Build 184)