v_1
v_1
pRBE2F = aCYCEcdk21 + E2F
v_10
CYCDcdk4 = xvar
v_11
xvar = p27
v_12
v_12
p27 = xvar
v_13
aCYCEcdk2 + p27 = CYCEcdk2p27
v_14
CYCEcdk2p27 = aCYCEcdk2 + p27
v_15
aCYCEcdk20 + CYCDcdk4 = xvar
v_16
xvar = E2F
v_17
CYCDcdk4 + p27 = CYCDcdk4p27
v_18
CYCDcdk4p27 = CYCDcdk4 + p27
v_19
aCYCEcdk2 = xvar
v_2
E2F + pRB = pRBE2F
v_20
p27 = xvar
v_21
xvar = aCYCEcdk20
v_22
aCYCEcdk20 = xvar
v_23
v_23
xvar = aCYCEcdk20
v_24
v_24
xvar = pRB
v_25
xvar = pRB
v_26
pRB = xvar
v_27
aCYCEcdk21 = pRB
v_3
iCYCEcdk2 = aCYCEcdk2
v_4
aCYCEcdk2 = iCYCEcdk2
v_5
v_5
xvar = iCYCEcdk2
v_6
xvar = E2F
v_7
E2F = xvar
v_8
iCYCEcdk2 = xvar
v_9
xvar = CYCDcdk4
Note that constraints are not enforced in simulations. It remains the responsibility of the user to verify that simulation results satisfy these constraints.
The kinetic origins of the restriction point in the mammalian cell cycle.
Cell Prolif. 1999;
32
(5):
321-335
- PubMed: 10619492
- ISSN: 0960-7722
- URL: http://ncbi.nlm.nih.gov/pubmed/10619492
Abstract
A detailed model mechanism for the G1/S transition in the mammalian cell cycle is presented and analysed by computer simulation to investigate whether the kinetic origins of the restriction point (R-point) can be identified. The R-point occurs in mid-to-late G1 phase and marks the transition between mitogen-dependent to mitogen-independent progression of the cell cycle. For purposes of computer simulations, the R-point is defined as the first point in time after mitosis where cutting off mitogen stimulation does not prevent the cell reaching the threshold activity of cyclin-E/cdk2 required for entry into S phase. The key components of the network that generate a dynamic switching behaviour associated with the R-point include a positive feedback loop between cyclin-E/cdk2 and Cdc25A, along with the mutually negative interaction between the cdk inhibitor p27Kip1 and cyclin-E/cdk2. Simulations of the passage through the R-point were carried out and the factors affecting the position of the R-point in G1 are determined. The detailed model also shows various points in the network where the activation of cyclin-E/cdk2 can be initiated with or without the involvement of the retinoblastoma protein.
The SBML for this model was obtained from the BioModels database (BioModels ID: BIOMD0000000169)
Biomodels notes: The plots correspond to the time profiles of p27, E2F and cycE/CDK2 as depicted in Fig 5c of the paper. MathSBML was used to obtain simulation results.
JWS Online curation: This model was curated by reproducing the figures as described in the BioModels Notes. No additional changes were made.