Try the new BioModels platform (beta)
BioModels Database logo

BioModels Database

spacer

BIOMD0000000242 - Bai2003_G1phaseRegulation

 

 |   |   |  Send feedback
Reference Publication
Publication ID: 12695688
Bai S, Goodrich D, Thron CD, Tecarro E, Obeyesekere M.
Theoretical and experimental evidence for hysteresis in cell proliferation.
Cell Cycle 2003 Jan-Feb; 2(1): 46-52
Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA.  [more]
Model
Original Model: http://www.itb.cnr.it/cell...
Submitter: Vijayalakshmi Chelliah
Submission ID: MODEL1003050000
Submission Date: 05 Mar 2010 14:37:28 UTC
Last Modification Date: 14 Feb 2014 13:22:55 UTC
Creation Date: 05 Mar 2010 16:22:00 UTC
Encoders:  Vijayalakshmi Chelliah
   Mandri Obeyeseker
set #1
bqmodel:isDerivedFrom BioModels Database Obeyesekere1999_CellCycle
set #2
bqbiol:hasTaxon Taxonomy Murinae
bqbiol:isVersionOf Reactome REACT_1590
Gene Ontology obsolete regulation of transcription involved in G1 phase of mitotic cell cycle
Notes

This a model from the article:
Theoretical and experimental evidence for hysteresis in cell proliferation.
Bai S, Goodrich D, Thron CD, Tecarro E, Obeyesekere M. Cell Cycle. 2003 Jan-Feb;2(1):46-52. 12695688 ,
Abstract:
We propose a mathematical model for the regulation of the G1-phase of the mammalian cell cycle taking into account interactions of cyclin D/cdk4, cyclin E/cdk2, Rb and E2F. Mathematical analysis of this model predicts that a change in the proliferative status in response to a change in concentrations of serum growth factors will exhibit the property of hysteresis: the concentration of growth factors required to induce proliferation is higher than the concentration required to maintain proliferation. We experimentally confirmed this prediction in mouse embryonic fibroblasts in vitro. In agreement with the mathematical model, this indicates that changes in proliferative mode caused by small changes in concentrations of growth factors are not easily reversible. Based on this study, we discuss the importance of proliferation hysteresis for cell cycle regulation.


The original model was taken from the Cell Cycle DataBase (CCDB).

Variable added: assignment rule for denoting phosphorylated Rb (Rb_phosphorylated i.e(RT-RS-R)) created.

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: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.

Model
Publication ID: 12695688 Submission Date: 05 Mar 2010 14:37:28 UTC Last Modification Date: 14 Feb 2014 13:22:55 UTC Creation Date: 05 Mar 2010 16:22:00 UTC
Mathematical expressions
Reactions
cyclinD synthesis cyclinD degradation cyclinE synthesis cyclinE degradation
pRB synthesis pRB/E2F complex association pRB/E2F complex dissociation via cyclin D pRB/E2F complex dissociation via cyclin E
E2F synthesis E2F degradation via cell cycle progression cell cycle progression go cell cycle progression slow
Rules
Assignment Rule (variable: Rb_phosphorylated)      
Physical entities
Compartments Species
cell D E R
RS theta X
Global parameters
GF k1 dD aD
aE k2 aF pX
RT qX pS pD
qD pE qE atheta
k3 dtheta qtheta aX
f g dX dE
fe Rb_phosphorylated    
Reactions (12)
 
 cyclinD synthesis  → [D];  
 
 cyclinD degradation [D] → ;   {D} , {E}
 
 cyclinE synthesis  → [E];   {theta}
 
 cyclinE degradation [E] → ;   {X} , {E}
 
 pRB synthesis  → [R];   {RS} , {R} , {X}
 
 pRB/E2F complex association [R] + [theta] → [RS];  
 
 pRB/E2F complex dissociation via cyclin D [RS] → [theta];   {RS} , {D}
 
 pRB/E2F complex dissociation via cyclin E [RS] → [theta];   {RS} , {E}
 
 E2F synthesis  → [theta];   {theta}
 
 E2F degradation via cell cycle progression [theta] → ;   {theta} , {X}
 
 cell cycle progression go  → [X];   {E} , {theta} , {X}
 
 cell cycle progression slow [X] → ;   {X}
 
Rules (1)
 
 Assignment Rule (name: Rb_phos) Rb_phosphorylated = (RT_1-RS_1)-R_1
 
Functions (1)
 
 Mass_Action_2 lambda(k1, S1, S2, k1*S1*S2)
 
 cell Spatial dimensions: 3.0  Compartment size: 1.0
 
 D
Compartment: cell
Initial amount: 0.0
 
 E
Compartment: cell
Initial amount: 0.0
 
 R
Compartment: cell
Initial amount: 2.5
 
 RS
Compartment: cell
Initial amount: 0.0
 
 theta
Compartment: cell
Initial amount: 0.0
 
   X
Compartment: cell
Initial amount: 0.0
 
Global Parameters (26)
 
   GF
Value: 6.3
Constant
 
   k1
Value: 0.05
Constant
 
   dD
Value: 0.4
Constant
 
   aD
Value: 0.4
Constant
 
   aE
Value: 0.16
Constant
 
   k2
Value: 1000.0
Constant
 
   aF
Value: 0.9
Constant
 
   pX
Value: 0.48
Constant
 
   RT
Value: 2.5
Constant
 
   qX
Value: 0.8
Constant
 
   pS
Value: 0.6
Constant
 
   pD
Value: 0.48
Constant
 
   qD
Value: 0.6
Constant
 
   pE
Value: 0.096
Constant
 
   qE
Value: 0.6
Constant
 
   atheta
Value: 0.05
Constant
 
   k3
Value: 1.5
Constant
 
   dtheta
Value: 0.12
Constant
 
   qtheta
Value: 0.3
Constant
 
   aX
Value: 0.08
Constant
 
   f
Value: 0.35
Constant
 
   g
Value: 0.528
Constant
 
   dX
Value: 1.04
Constant
 
   dE
Value: 0.2
Constant
 
   fe
Value: 0.003
Constant
 
   Rb_phosphorylated
Value: NaN
 
Representative curation result(s)
Representative curation result(s) of BIOMD0000000242

Curator's comment: (updated: 08 Mar 2010 12:06:14 GMT)

The model reproduces figure 2 of the reference publication. The model was integrated and simulated using Copasi v4.5 (Build 30).

spacer
spacer