deineko1

The SBML for this model was obtained from the BioModels database (BioModels ID: BIOMD0000000208). Biomodels notes: "The model reproduces Fig 3 of the paper corresponding to the transition to S phase. Units have not been defined for this model because the paper mentions the use of arbitrary units for the various species and parameters." JWS Online curation: This model was curated by reproducing the figures as described in the BioModels Notes. No additional changes were made.

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Modeling dynamics of gene net, regulating the cell cycle in mammalian cells.

  • IV Deĭneko
  • AE Kel'
  • OV Kel'-Margulis
  • E Wingender
  • VA Ratner
Genetika 2003; 39 (9): 1285-1292
Abstract
The study of the molecular mechanisms determining cellular programs of proliferation, differentiation, and apoptosis is currently attracting much attention. Recent studies have demonstrated that the system of cell-cycle control based on the transcriptional regulation of the expression of specific genes is responsible for the transition between programs. These groups of functionally connected genes from so-called gene networks characterized by numerous feedbacks and a complex behavioral dynamics. Computer simulation methods have been applied to studying the dynamics of gene networks regulating the cell cycle of vertebrates. The data on the regulation of the key genes obtained from the CYCLE-TRRD database have been used as a basis to construct gene networks of different degrees of complexity controlling the G1/S transition, one of the most important stages of the cell cycle. The behavior dynamics of the model constructed has been analyzed. Two qualitatively different functional modes of the system has been obtained. It has also been shown that the transition between these modes depends on the duration of the proliferation signal. It has also been demonstrated that the additional feedback from factor E2F to genes c-fos and c-jun, which was predicted earlier based on the computer analysis of promoters, plays an important role in the transition of the cell to the S phase.

Unit definitions have no effect on the numerical analysis of the model. It remains the responsibility of the modeler to ensure the internal numerical consistency of the model. If units are provided, however, the consistency of the model units will be checked.

Name Definition
Id Name Spatial dimensions Size
compartment 3.0 1.0
Id Name Initial quantity Compartment Fixed
y1 E2F 0.014 compartment
y2 pRB 0.006 compartment
y3 Phosphorylated pRB 0.0 compartment
y4 inactive cycE_cdk2 0.0 compartment
y5 active cycE_cdk2 0.0001 compartment
y6 AP-1 0.0 compartment

Initial assignments are expressions that are evaluated at time=0. It is not recommended to create initial assignments for all model entities. Restrict the use of initial assignments to cases where a value is expressed in terms of values or sizes of other model entities. Note that it is not permitted to have both an initial assignment and an assignment rule for a single model entity.

Definition
Id Name Objective coefficient Reaction Equation and Kinetic Law Flux bounds
R1 ∅ > y1

emax * k1 * y1 / (k1 * y1 + (k1_prime + k1_double_prime * y1) * y2)
R10 y5 > y4

k4a * y5
R11 y4 > ∅

phi4i * y4
R12 y5 > ∅

phi4a * y5
R13 ∅ > y6

k6 * y1
R14 ∅ > y6

F6
R15 y6 > ∅

phi6 * y6
R2 y1 > ∅

phi1 * y1
R3 ∅ > y2

k2 * y1
R4 y2 > y3

k3 * y2 * y5
R5 y2 > ∅

phi2 * y2
R6 y3 > ∅

phi3 * y3
R7 ∅ > y4

k4 * y1
R8 ∅ > y4

k4_double_prime * y6
R9 y4 > y5

k4i * y4 * y5

Global parameters

Id Value
F6 0.044
emax 2.0
k1 1.0
k1_double_prime 10.0
k1_prime 1.0
k2 1.0
k3 0.4
k4 0.09
k4_double_prime 0.1
k4a 2.0
k4i 1.0
k6 0.0
phi1 0.1
phi2 0.01
phi3 0.1
phi4a 0.01
phi4i 0.01
phi6 0.1

Local parameters

Id Value Reaction

Assignment rules

Definition
F6 = piecewise(0.044, leq(time, 60.0), 0.0)

Rate rules

Definition

Algebraic rules

Definition
Trigger Assignments