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BIOMD0000000228 - Swat2004_Mammalian_G1_S_Transition

 

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Reference Publication
Publication ID: 15231543
Swat M, Kel A, Herzel H.
Bifurcation analysis of the regulatory modules of the mammalian G1/S transition.
Bioinformatics 2004 Jul; 20(10): 1506-1511
Institute for Theoretical Biology, Humboldt University Berlin, Invalidenstrasse 43, Berlin, D-10115, Germany. swat@itb.biologie.hu-berlin.de  [more]
Model
Original Model: http://www.itb.cnr.it/cell...
Submitter: Nicolas Le Novère
Submission ID: MODEL3897709120
Submission Date: 25 Mar 2009 09:37:21 UTC
Last Modification Date: 09 Aug 2012 16:28:08 UTC
Creation Date: 17 Aug 2009 14:15:15 UTC
Encoders:  Lukas Endler
set #1
bqbiol:hasTaxon Taxonomy Mammalia
bqbiol:isVersionOf Gene Ontology regulation of transcription involved in G1/S transition of mitotic cell cycle
bqbiol:isPartOf Reactome REACT_1783
Notes

This is the extended model described the article:
Bifurcation analysis of the regulatory modules of the mammalian G1/S transition.
Swat M, Kel A, Herzel H. Bioinformatics 2004 Jul 10;20(10):1506-11. PMID: 15231543 , doi: 10.1093/bioinformatics/bth110
Abstract:
MOTIVATION: Mathematical models of the cell cycle can contribute to an understanding of its basic mechanisms. Modern simulation tools make the analysis of key components and their interactions very effective. This paper focuses on the role of small modules and feedbacks in the gene-protein network governing the G1/S transition in mammalian cells. Mutations in this network may lead to uncontrolled cell proliferation. Bifurcation analysis helps to identify the key components of this extremely complex interaction network.
RESULTS: We identify various positive and negative feedback loops in the network controlling the G1/S transition. It is shown that the positive feedback regulation of E2F1 and a double activator-inhibitor module can lead to bistability. Extensions of the core module preserve the essential features such as bistability. The complete model exhibits a transcritical bifurcation in addition to bistability. We relate these bifurcations to the cell cycle checkpoint and the G1/S phase transition point. Thus, core modules can explain major features of the complex G1/S network and have a robust decision taking function.

This model originates from BioModels Database: A Database of Annotated Published Models. It is copyright (c) 2005-2010 The BioModels Team.
To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not..

To cite BioModels Database, please use Le Novère N., Bornstein B., Broicher A., Courtot M., Donizelli M., Dharuri H., Li L., Sauro H., Schilstra M., Shapiro B., Snoep J.L., Hucka M. (2006) BioModels Database: A Free, Centralized Database of Curated, Published, Quantitative Kinetic Models of Biochemical and Cellular Systems Nucleic Acids Res., 34: D689-D691.

Model
Publication ID: 15231543 Submission Date: 25 Mar 2009 09:37:21 UTC Last Modification Date: 09 Aug 2012 16:28:08 UTC Creation Date: 17 Aug 2009 14:15:15 UTC
Mathematical expressions
Reactions
pRB synthesis pRB phosphorylation pRBp dephosphorylation pRB degradation
E2F1 synthesis E2F1 degradation CycD synthesis CycD inibition
CycD activation CycD degradation CycD degradation2 AP1 synthesis
Ap1 degradation pRBp phosphorylation pRBpp dephosphorylation pRBpp degradation
pRBp degradation CycE synthesis CycE activation CycE inibition
CycE degradation CycE degradation2    
Physical entities
Compartments Species
cell pRB pRBp E2F1
CycD/cdk4,6(i) CycD/cdk4,6(a) AP1
pRBpp CycE/cdk2(i) CycEa/cdk2(a)
Global parameters
k1 Km1 J11 J61
k16 k61 phi_pRB kp
k2 a Km2 J12
J62 phi_E2F1 k3 k23
J13 J63 k34 Km4
phi_CycDi k43 phi_CycDa Fm
k25 J15 J65 phi_AP1
k67 k76 phi_pRBpp phi_pRBp
k28 J18 J68 k89
Km9 k98 phi_CycEi phi_CycEa
Reactions (22)
 
 pRB synthesis  → [pRB];   {pRB} , {pRBp} , {E2F1}
 
 pRB phosphorylation [pRB] → [pRBp];   {pRB} , {CycD/cdk4,6(a)}
 
 pRBp dephosphorylation [pRBp] → [pRB];  
 
 pRB degradation [pRB] → ;  
 
 E2F1 synthesis  → [E2F1];   {E2F1} , {pRB} , {pRBp}
 
 E2F1 degradation [E2F1] → ;  
 
 CycD synthesis  → [CycD/cdk4,6(i)];   {E2F1} , {pRB} , {pRBp} , {AP1}
 
 CycD inibition [CycD/cdk4,6(a)] → [CycD/cdk4,6(i)];  
 
 CycD activation [CycD/cdk4,6(i)] → [CycD/cdk4,6(a)];   {CycD/cdk4,6(i)} , {CycD/cdk4,6(a)}
 
 CycD degradation [CycD/cdk4,6(i)] → ;  
 
 CycD degradation2 [CycD/cdk4,6(a)] → ;  
 
 AP1 synthesis  → [AP1];   {E2F1} , {pRB} , {pRBp}
 
 Ap1 degradation [AP1] → ;  
 
 pRBp phosphorylation [pRBp] → [pRBpp];   {pRBp} , {CycEa/cdk2(a)}
 
 pRBpp dephosphorylation [pRBpp] → [pRBp];  
 
 pRBpp degradation [pRBpp] → ;  
 
 pRBp degradation [pRBp] → ;  
 
 CycE synthesis  → [CycE/cdk2(i)];   {E2F1} , {pRB} , {pRBp}
 
 CycE activation [CycE/cdk2(i)] → [CycEa/cdk2(a)];   {CycE/cdk2(i)} , {CycEa/cdk2(a)}
 
 CycE inibition [CycEa/cdk2(a)] → [CycE/cdk2(i)];  
 
 CycE degradation [CycE/cdk2(i)] → ;  
 
 CycE degradation2 [CycEa/cdk2(a)] → ;  
 
   cell Spatial dimensions: 3.0  Compartment size: 1.0
 
 pRB
Compartment: cell
Initial concentration: 0.1
 
 pRBp
Compartment: cell
Initial concentration: 0.1
 
 E2F1
Compartment: cell
Initial concentration: 0.1
 
 CycD/cdk4,6(i)
Compartment: cell
Initial concentration: 0.1
 
 CycD/cdk4,6(a)
Compartment: cell
Initial concentration: 0.1
 
 AP1
Compartment: cell
Initial concentration: 0.1
 
 pRBpp
Compartment: cell
Initial concentration: 0.1
 
 CycE/cdk2(i)
Compartment: cell
Initial concentration: 0.1
 
 CycEa/cdk2(a)
Compartment: cell
Initial concentration: 0.1
 
Global Parameters (40)
 
   k1
Value: 1.0
Constant
 
   Km1
Value: 0.5
Constant
 
   J11
Value: 0.5
Constant
 
   J61
Value: 5.0
Constant
 
   k16
Value: 0.4
Constant
 
   k61
Value: 0.3
Constant
 
   phi_pRB
Value: 0.005
Constant
 
   kp
Value: 0.05
Constant
 
   k2
Value: 1.6
Constant
 
   a
Value: 0.04
Constant
 
   Km2
Value: 4.0
Constant
 
   J12
Value: 5.0
Constant
 
   J62
Value: 8.0
Constant
 
   phi_E2F1
Value: 0.1
Constant
 
   k3
Value: 0.05
Constant
 
   k23
Value: 0.3
Constant
 
   J13
Value: 0.002
Constant
 
   J63
Value: 2.0
Constant
 
   k34
Value: 0.04
Constant
 
   Km4
Value: 0.3
Constant
 
   phi_CycDi
Value: 0.023
Constant
 
   k43
Value: 0.01
Constant
 
   phi_CycDa
Value: 0.03
Constant
 
 Fm
Value: 0.005
Constant
 
   k25
Value: 0.9
Constant
 
   J15
Value: 0.001
Constant
 
   J65
Value: 6.0
Constant
 
   phi_AP1
Value: 0.01
Constant
 
   k67
Value: 0.7
Constant
 
   k76
Value: 0.1
Constant
 
   phi_pRBpp
Value: 0.04
Constant
 
   phi_pRBp
Value: 0.06
Constant
 
   k28
Value: 0.06
Constant
 
   J18
Value: 0.6
Constant
 
   J68
Value: 7.0
Constant
 
   k89
Value: 0.07
Constant
 
   Km9
Value: 0.005
Constant
 
   k98
Value: 0.01
Constant
 
   phi_CycEi
Value: 0.06
Constant
 
   phi_CycEa
Value: 0.05
Constant
 
Representative curation result(s)
Representative curation result(s) of BIOMD0000000228

Curator's comment: (updated: 18 Aug 2009 15:26:56 BST)

Reproduction of figure 5a from the original publication. The results were calculated using the AUTO 2000 front-end of Systems Biology Workbench created by Frank Bergman.

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