obeyesekere

v_1

source = CYCD1cdk4

v_10

v_10

source = MPF

v_11

MPF = sink

v_2

v_2

CYCD1cdk4 = sink

v_3

v_3

source = CYCEcdk2

v_4

v_4

CYCEcdk2 = sink

v_5

v_5

source = Rbhypo + unphosRb

v_6

Rbhypo + freeE2F = RbE2F

v_7

v_7

RbE2F + unphosRb = freeE2F

v_8

v_8

source = MPF

v_9

v_9

source = MPF

Global parameters

Note that constraints are not enforced in simulations. It remains the responsibility of the user to verify that simulation results satisfy these constraints.


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Abstract
A mathematical model integrating the roles of cyclin D, cdk4, cyclin E, cdk2, E2F and RB in control of the G1 phase of the cell cycle is described. Experimental results described with murine embryo fibroblasts (MEFs), either Rb+/+ or Rb-/-, and with the RB-deficient osteosarcoma cell line, Saos-2, served as the basis for the formulation of this mathematical model. A model employing the known interactions of these six proteins does not reproduce the experimental observations described in the MEFs. The appropriate modelling of G1 requires the inclusion of a sensing mechanism which adjusts the activity of cyclin E/cdk2 in response to both RB concentration and growth factors. Incorporation of this sensing mechanism into the model allows it to reproduce most of the experimental results observed in Saos-2 cells, Rb-/- MEFS, and Rb+/+ MEFs. The model also makes specific predictions which have not been tested experimentally.

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