Dong2018 - E2F dynamics in G1 phase

  public model
Model Identifier
MODEL1811050001
Short description

The length of the G1 phase in the cell cycle shows significant variability in different cell types and tissue types. To gain insights into the control of G1 length, we generated an E2F activity reporter that captures free E2F activity after dissociation from Rb sequestration and followed its kinetics of activation at the single-cell level, in real time. Our results demonstrate that its activity is precisely coordinated with S phase progression. Quantitative analysis indicates that there is a pre-S phase delay between E2F transcriptional dynamic and activity dynamics. This delay is variable among different cell types and is strongly modulated by the cyclin D/CDK4/6 complex activity through Rb phosphorylation. Our findings suggest that the main function of this complex is to regulate the appropriate timing of G1 length.

Format
SBML (L2V4)
Related Publication
  • Cyclin D/CDK4/6 activity controls G1 length in mammalian cells.
  • Dong P, Zhang C, Parker BT, You L, Mathey-Prevot B
  • PloS one , 1/ 2018 , Volume 13 , Issue 1 , pages: e0185637 , PubMed ID: 29309421
  • Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC, United States of America.
  • The length of the G1 phase in the cell cycle shows significant variability in different cell types and tissue types. To gain insights into the control of G1 length, we generated an E2F activity reporter that captures free E2F activity after dissociation from Rb sequestration and followed its kinetics of activation at the single-cell level, in real time. Our results demonstrate that its activity is precisely coordinated with S phase progression. Quantitative analysis indicates that there is a pre-S phase delay between E2F transcriptional dynamic and activity dynamics. This delay is variable among different cell types and is strongly modulated by the cyclin D/CDK4/6 complex activity through Rb phosphorylation. Our findings suggest that the main function of this complex is to regulate the appropriate timing of G1 length.
Contributors
Submitter of the first revision: Ashley Xavier
Submitter of this revision: Ashley Xavier
Modellers: Ashley Xavier

Metadata information

isDescribedBy (2 statements)
hasTaxon (2 statements)
Taxonomy Homo sapiens
Taxonomy Rattus norvegicus


Curation status
Non-curated

Tags

Connected external resources

SBGN view in Newt Editor

Name Description Size Actions

Model files

Dong2018_final.xml SBML lvl2 file containing the model 87.61 KB Preview | Download

Additional files

Dong2018.cps copasi file to generate figure 3 g 137.82 KB Preview | Download

  • Model originally submitted by : Ashley Xavier
  • Submitted: Nov 7, 2018 1:26:16 PM
  • Last Modified: Nov 7, 2018 1:26:16 PM
Revisions
  • Version: 6 public model Download this version
    • Submitted on: Nov 7, 2018 1:26:16 PM
    • Submitted by: Ashley Xavier
    • With comment: Edited model metadata online.
Curator's comment:
(added: 05 Nov 2018, 16:56:18, updated: 22 Jan 2019, 17:20:06)
When using copasi to simulate from SBML file, requires checking the "Fire at initial Time if Trigger true" option for "Pre E2Fm trancription" in Events The model was simulated in COPASI 4.24 and plotted in R 3.5.1 . Figure 3h of the reference publication which cannot be accurately reproduced is represented on the right side.