Linke2017 - Synchronization of Cyclins' expression by the Fkh2 transcription factor in the budding yeast cell cycle

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Model Identifier
BIOMD0000000934
Short description

Modeling of the expression of cyclin B2 and B3 in the budding yeast cell cycle
Format
SBML (L2V3)
Related Publication
  • A Clb/Cdk1-mediated regulation of Fkh2 synchronizes CLB expression in the budding yeast cell cycle.
  • Linke C, Chasapi A, González-Novo A, Al Sawad I, Tognetti S, Klipp E, Loog M, Krobitsch S, Posas F, Xenarios I, Barberis M
  • NPJ Systems Biology and Applications , 1/ 2017 , Volume 3 , pages: 7 , PubMed ID: 28649434
  • Max Planck Institute for Molecular Genetics, Berlin, 14195 Germany.
  • Precise timing of cell division is achieved by coupling waves of cyclin-dependent kinase (Cdk) activity with a transcriptional oscillator throughout cell cycle progression. Although details of transcription of cyclin genes are known, it is unclear which is the transcriptional cascade that modulates their expression in a timely fashion. Here, we demonstrate that a Clb/Cdk1-mediated regulation of the Fkh2 transcription factor synchronizes the temporal mitotic CLB expression in budding yeast. A simplified kinetic model of the cyclin/Cdk network predicts a linear cascade where a Clb/Cdk1-mediated regulation of an activator molecule drives CLB3 and CLB2 expression. Experimental validation highlights Fkh2 as modulator of CLB3 transcript levels, besides its role in regulating CLB2 expression. A Boolean model based on the minimal number of interactions needed to capture the information flow of the Clb/Cdk1 network supports the role of an activator molecule in the sequential activation, and oscillatory behavior, of mitotic Clb cyclins. This work illustrates how transcription and phosphorylation networks can be coupled by a Clb/Cdk1-mediated regulation that synchronizes them.
Contributors
Submitter of the first revision: Matthieu MAIRE
Submitter of this revision: Ahmad Zyoud
Modellers: Matthieu MAIRE, Ahmad Zyoud

Metadata information

is (2 statements)
BioModels Database BIOMD0000000934
BioModels Database MODEL1809050002

isDescribedBy (1 statement)
PubMed 28649434

hasPart (1 statement)
Gene Ontology regulation of cell cycle

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

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

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Model files
Linke2017.xml SBML L2V3 representation of Linke2017 - Synchronization of Cyclins\ expression by the Fkh2 transcription factor in the budding yeast cell cycle 80.81 KB Preview | Download

Additional files
Linke2017_figure1b.cps COPASI version 4.27 (Build 217) for reproducing figure 1b in the reference publication. 133.67 KB Preview | Download
Linke2017_figure1c.cps COPASI version 4.27 (Build 217) for reproducing figure 1c in the reference publication. 133.66 KB Preview | Download
Linke2017_figure1c.sedml SEDML file for reproducing figure 1c in the reference publication. 2.84 KB Preview | Download
Linke2017_figure1d.cps COPASI version 4.27 (Build 217) for reproducing figure 1d in the reference publication. 133.66 KB Preview | Download
Linke2017_figure1d.sedml SEDML file for reproducing figure 1d in the reference publication. 2.84 KB Preview | Download
Linke2017_figure1e.cps COPASI version 4.27 (Build 217) for reproducing figure 1e in the reference publication. 133.66 KB Preview | Download
Linke2017_figure1e.sedml SEDML file for reproducing figure 1e in the reference publication. 2.84 KB Preview | Download
Linke2017f1b.sedml SEDML file for reproducing figure 1b in the reference publication. 2.84 KB Preview | Download

  • Model originally submitted by : Matthieu MAIRE
  • Submitted: Sep 5, 2018 4:35:02 PM
  • Last Modified: Apr 24, 2020 3:32:00 PM
Revisions
  • Version: 4 public model Download this version
    • Submitted on: Apr 24, 2020 3:32:00 PM
    • Submitted by: Ahmad Zyoud
    • With comment: Automatically added model identifier BIOMD0000000934
  • Version: 2 public model Download this version
    • Submitted on: Sep 5, 2018 4:35:02 PM
    • Submitted by: Matthieu MAIRE
    • With comment: Edited model metadata online.

(*) 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
Cdk1 Clb5or6

Cyclin-dependent kinase 1 ; S-phase entry cyclin-5 ; protein-containing complex 		0.0 mmol
Sic1

Protein SIC1 		5.0 mmol
Cdk1 Clb1or2

G2/mitotic-specific cyclin-2 ; Cyclin-dependent kinase 1 ; protein-containing complex 		0.0 mmol
Cdk1 Clb1or2 Sic1

Cyclin-dependent kinase 1 ; Protein SIC1 ; G2/mitotic-specific cyclin-2 ; protein-containing complex 		0.0 mmol
Cdk1 Clb5or6 Sic1

Protein SIC1 ; Cyclin-dependent kinase 1 ; S-phase entry cyclin-5 ; protein-containing complex 		0.0 mmol
Clb5or6 degraded

S-phase entry cyclin-5 ; Removed 		0.0 mmol
Cdk1 Clb3or4

G2/mitotic-specific cyclin-3 ; Cyclin-dependent kinase 1 ; protein-containing complex 		0.0 mmol
Cdk1 Clb3or4 Sic1

G2/mitotic-specific cyclin-3 ; Cyclin-dependent kinase 1 ; Protein SIC1 ; protein-containing complex 		0.0 mmol
Reactions
Reactions Rate Parameters
Sic1 + Cdk1_Clb5or6 => Cdk1_Clb5or6_Sic1 cell*k2*Sic1*Cdk1_Clb5or6 k2 = 5.0
Cdk1_Clb3or4_Sic1 => Sic1 + Cdk1_Clb3or4 cell*k16*Cdk1_Clb3or4_Sic1 k16 = 0.5
=> Cdk1_Clb1or2; Cdk1_Clb1or2, Cdk1_Clb3or4, Cdk1_Clb5or6 cell*k9*(1+kD*Cdk1_Clb1or2+kB*Cdk1_Clb3or4+kC*Cdk1_Clb5or6) kB = 1000.0; kC = 100.0; k9 = 0.001; kD = 100.0
Cdk1_Clb1or2_Sic1 => Sic1_degraded_re14; Cdk1_Clb5or6, Cdk1_Clb3or4, Cdk1_Clb1or2 cell*k14*Cdk1_Clb1or2_Sic1*(1+Cdk1_Clb5or6+Cdk1_Clb3or4+Cdk1_Clb1or2) k14 = 0.05
Cdk1_Clb5or6_Sic1 => Sic1 + Cdk1_Clb5or6 cell*k3*Cdk1_Clb5or6_Sic1 k3 = 0.5
Cdk1_Clb5or6 => Clb5or6_degraded cell*k6*Cdk1_Clb5or6 k6 = 0.7
Cdk1_Clb3or4 => Clb3or4_degraded cell*k8*Cdk1_Clb3or4 k8 = 0.7
Cdk1_Clb3or4_Sic1 => Sic1_degraded_re18; Cdk1_Clb5or6, Cdk1_Clb3or4, Cdk1_Clb1or2 cell*k18*Cdk1_Clb3or4_Sic1*(1+Cdk1_Clb5or6+Cdk1_Clb3or4+Cdk1_Clb1or2) k18 = 0.05
Sic1 + Cdk1_Clb3or4 => Cdk1_Clb3or4_Sic1 cell*k15*Sic1*Cdk1_Clb3or4 k15 = 5.0
Curator's comment:
(added: 05 Sep 2018, 16:36:30, updated: 24 Apr 2020, 15:31:42)
Figure 1b,c,d,e of the reference publication has been reproduced using Copasi 4.27 Build 217. Use attach SEDML file to reproduce the figure.