Gerard2010 - Progression of mammalian cell cycle by successive activation of various cyclin cdk complexes

  public model
Model Identifier
BIOMD0000000941
Short description 
We previously proposed a detailed, 39-variable model for the network of cyclin-dependent kinases (Cdks) that controls progression along the successive phases of the mammalian cell cycle. Here, we propose a skeleton, 5-variable model for the Cdk network that can be seen as the backbone of the more detailed model for the mammalian cell cycle. In the presence of sufficient amounts of growth factor, the skeleton model also passes from a stable steady state to sustained oscillations of the various cyclin/Cdk complexes. This transition corresponds to the switch from quiescence to cell proliferation. Sequential activation of the cyclin/Cdk complexes allows the ordered progression along the G1, S, G2 and M phases of the cell cycle. The 5-variable model can also account for the existence of a restriction point in G1, and for endoreplication. Like the detailed model, it contains multiple oscillatory circuits and can display complex oscillatory behaviour such as quasi-periodic oscillations and chaos. We compare the dynamical properties of the skeleton model with those of the more detailed model for the mammalian cell cycle.
Format
SBML (L2V4)
Related Publication
  • A skeleton model for the network of cyclin-dependent kinases driving the mammalian cell cycle.
  • Gérard C, Goldbeter A
  • Interface focus , 2/ 2011 , Volume 1 , Issue 1 , pages: 24-35 , PubMed ID: 22419972
  • Faculté des Sciences , Université Libre de Bruxelles (ULB) , Campus Plaine, CP 231, 1050 Brussels , Belgium.
  • We previously proposed a detailed, 39-variable model for the network of cyclin-dependent kinases (Cdks) that controls progression along the successive phases of the mammalian cell cycle. Here, we propose a skeleton, 5-variable model for the Cdk network that can be seen as the backbone of the more detailed model for the mammalian cell cycle. In the presence of sufficient amounts of growth factor, the skeleton model also passes from a stable steady state to sustained oscillations of the various cyclin/Cdk complexes. This transition corresponds to the switch from quiescence to cell proliferation. Sequential activation of the cyclin/Cdk complexes allows the ordered progression along the G1, S, G2 and M phases of the cell cycle. The 5-variable model can also account for the existence of a restriction point in G1, and for endoreplication. Like the detailed model, it contains multiple oscillatory circuits and can display complex oscillatory behaviour such as quasi-periodic oscillations and chaos. We compare the dynamical properties of the skeleton model with those of the more detailed model for the mammalian cell cycle.
Contributors
Submitter of the first revision: Matthieu MAIRE
Submitter of this revision: Ahmad Zyoud
Modellers: Tung Nguyen, Matthieu MAIRE, Ahmad Zyoud

Metadata information

is (2 statements)
BioModels Database BIOMD0000000941
BioModels Database MODEL1809060001

hasTaxon (1 statement)
Taxonomy Mammalia

hasPart (1 statement)
Gene Ontology regulation of cell cycle

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

isDescribedBy (2 statements)
Curation status
Curated
Modelling approach(es)
ordinary differential equation model
Tags

Connected external resources

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Model files
gerard2010.xml SBML L2V4 representation of Gerard2010 - Progression of mammalian cell cycle by successive activation of various cyclin cdk complexes 72.53 KB Preview | Download

Additional files
gerard2010.cps COPASI version 4.27 (Build 217) file for reproducing figure 4B in the reference publication. 113.04 KB Preview | Download
gerard2010.sedml sed-ml L1V2 for reproducing figure 4B in the reference publication. 2.94 KB Preview | Download

  • Model originally submitted by : Matthieu MAIRE
  • Submitted: Sep 6, 2018 11:55:10 AM
  • Last Modified: Apr 30, 2020 6:03:22 PM
Revisions
  • Version: 5 public model Download this version
    • Submitted on: Apr 30, 2020 6:03:22 PM
    • Submitted by: Ahmad Zyoud
    • With comment: Automatically added model identifier BIOMD0000000941
  • Version: 3 public model Download this version
    • Submitted on: Apr 30, 2020 5:29:27 PM
    • Submitted by: Tung Nguyen
    • With comment: Automatically added model identifier BIOMD0000000941
  • Version: 2 public model Download this version
    • Submitted on: Sep 6, 2018 11:55:10 AM
    • Submitted by: Matthieu MAIRE
    • With comment: Edited model metadata online.

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Legends
: Variable used inside SBML models


Species
Species Initial Concentration/Amount
transcription factor E2F active

Transcription factor E2F1 ; active 		2.4855 mmol
Cdc20 active

Cell division cycle protein 20 homolog ; active ; phosphorylated 		0.5 mmol
cyclin B Cdk1

Cyclin-dependent kinase 1 ; G2/mitotic-specific cyclin-B1 ; protein-containing complex 		1.0 mmol
cyclin E Cdk2

G1/S-specific cyclin-E1 ; Cyclin-dependent kinase 2 ; protein-containing complex 		2.0 mmol
cyclin A Cdk2

Cyclin-dependent kinase 2 ; Cyclin-A2 ; protein-containing complex 		2.6 mmol
cyclin D Cdk4 6

G1/S-specific cyclin-D1 ; Cyclin-dependent kinase 4 ; protein-containing complex 		0.7205 mmol
Reactions
Reactions Rate Parameters
=> transcription_factor_E2F_active; E2F_total, cyclin_D_Cdk4_6, cyclin_E_Cdk2 nuclear*V1e2f*(E2F_total-transcription_factor_E2F_active)/((K1e2f+E2F_total)-transcription_factor_E2F_active)*(cyclin_D_Cdk4_6+cyclin_E_Cdk2) K1e2f = 0.01; V1e2f = 0.805
=> Cdc20_active; cyclin_B_Cdk1, Cdc20_total nuclear*V1cdc20*cyclin_B_Cdk1*(Cdc20_total-Cdc20_active)/(K1cdc20+(Cdc20_total-Cdc20_active)) K1cdc20 = 1.0; V1cdc20 = 0.21
cyclin_B_Cdk1 => ; Cdc20_active nuclear*Vdb*Cdc20_active*cyclin_B_Cdk1/(Kdb+cyclin_B_Cdk1) Vdb = 0.28; Kdb = 0.005
Cdc20_active => nuclear*V2cdc20*Cdc20_active/(K2cdc20+Cdc20_active) K2cdc20 = 1.0; V2cdc20 = 0.35
=> cyclin_E_Cdk2; transcription_factor_E2F_active nuclear*vse*transcription_factor_E2F_active vse = 0.21
=> cyclin_A_Cdk2; transcription_factor_E2F_active nuclear*vsa*transcription_factor_E2F_active vsa = 0.175
cyclin_A_Cdk2 => ; Cdc20_active nuclear*Vda*Cdc20_active*cyclin_A_Cdk2/(Kda+cyclin_A_Cdk2) Vda = 0.245; Kda = 0.1
=> cyclin_B_Cdk1; cyclin_A_Cdk2 nuclear*vsb*cyclin_A_Cdk2 vsb = 0.21
cyclin_D_Cdk4_6 => ; cyclin_D_Cdk4_6 nuclear*Vdd*cyclin_D_Cdk4_6/(Kdd+cyclin_D_Cdk4_6) Kdd = 0.1; Vdd = 0.245
cyclin_E_Cdk2 => ; cyclin_A_Cdk2 nuclear*Vde*cyclin_A_Cdk2*cyclin_E_Cdk2/(Kde+cyclin_E_Cdk2) Kde = 0.1; Vde = 0.35
Curator's comment:
(added: 06 Sep 2018, 12:21:01, updated: 06 Sep 2018, 12:21:01)
Figure 4b of the reference publication has been reproduced using Copasi 4.23 Build 184. Use attached SEDML file to reproduce the figure 4b.