_1
cycD/CDK4 synthesis
∅ > D_1
_7
pRB/E2F complex deassociation via cycE/CDK2
RS_1 > ∅
cycECDK2degradation_1
cycE/CDK2 degradation
E_1 > ∅
cyclebreak_1
cycle break
X_1 > ∅
cycleprogression_1
cycle progression
∅ > X_1
cyclinCDK4degradation_1
cycD/CDK4 degradation
D_1 > ∅
cyclin_1
cycE/CDK2 synthesis
∅ > E_1
pRBE2Fcomplexassociation_1
pRB/E2F complex association
R_1 > RS_1
pRBE2FcomplexdeassociationviacycDCDK4_1
pRB/E2F complex deassociation via cycD/CDK4
RS_1 > ∅
pRBpdephosphorylation_1
pRB-p dephosphorilation
∅ > R_1
Assignment rules
RP_1 = RT_1 - RS_1 - R_1
E2F_1 = theta_1 - RS_1
unpho_RB = R_1 + RS_1
Function definitions
Note that constraints are not enforced in simulations. It remains the responsibility of the user to verify that simulation results satisfy these constraints.
A model of cell cycle behavior dominated by kinetics of a pathway stimulated by growth factors.
Bull. Math. Biol. 1999;
61
(5):
917-934
- PubMed: 17886749
- ISSN: 0092-8240
- URL: https://ncbi.nlm.nih.gov/pubmed/17886749
Abstract
A modified version of a previously developed mathematical model [Obeyesekere et al., Cell Prolif. (1997)] of the G1-phase of the cell cycle is presented. This model describes the regulation of the G1-phase that includes the interactions of the nuclear proteins, RB, cyclin E, cyclin D, cdk2, cdk4 and E2F. The effects of the growth factors on cyclin D synthesis under saturated or unsaturated growth factor conditions are investigated based on this model. The solutions to this model (a system of nonlinear ordinary differential equations) are discussed with respect to existing experiments. Predictions based on mathematical analysis of this model are presented. In particular, results are presented on the existence of two stable solutions, i.e., bistability within the G1-phase. It is shown that this bistability exists under unsaturated growth factor concentration levels. This phenomenon is very noticeable if the efficiency of the signal transduction, initiated by the growth factors leading to cyclin D synthesis, is low. The biological significance of this result as well as possible experimental designs to test these predictions are presented.
The SBML for this model was obtained from the BioModels database (BioModels ID: BIOMD0000000168).
Biomodels notes: "The model reproduces the time profiles of the different species depicted in Fig 3a of the paper. Model successfully reproduced using MathSBML."
JWS Online curation: This model was curated by reproducing the figures as described in the BioModels Notes. In order to reproduce Figure 3A the following initials values (as the manuscript states) were used: D[0] = 0.1, E[0] = 0.6, R[0] = 0.5, RS[0] = 1.0, X[0] = 0.7