A mathematical description of regulation of the G1-S transition of the mammalian cell cycle.
A mathematical model of regulation of the G1-S transition of the mammalian cell cycle has been formulated to organize available experimental molecular-level information in a systematic quantitative framework and to evaluate the ability of this manifestation of current knowledge to calculate correctly experimentally observed phenotypes. This model includes nine components and includes cyclin-cdk complexes, a pocket protein (pRb), a transcription factor (E2F-1), and a cyclin-cdk complex inhibitor. Simulation of the model equations yields stable oscillatory solutions corresponding to cell proliferation and asymptotically stable solutions corresponding to cell cycle arrest (quiescence). Bifurcation analysis of the system suggests changes in the intracellular concentrations of either E2F or cyclin E can activate cell proliferation and that co-overexpression of these molecules can prevent cell proliferation. Further analysis suggests that the amount of inhibitor necessary to prevent cell proliferation is independent of the concentrations of cyclin E and E2F and depends only on the equilibrium ratio between the bound and unbound forms of the inhibitor to the complex.
Hatzimanikatis
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Cargill Bioscience Division, Wayzata, Minnesota 55391-2397, USA.
Lee
K H
KH
Bailey
J E
JE
D000818:Animals; D042846:CDC2-CDC28 Kinases; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D002455:Cell Division; D019927:Cyclin E / Q000235:genetics / Q000378:metabolism; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D016193:G1 Phase; D007700:Kinetics; D008322:Mammals; D008954:Models, Biological; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism; D056465:Retinoblastoma-Binding Protein 1; D016196:S Phase; D013816:Thermodynamics; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D019927:Cyclin E; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D016160:Retinoblastoma Protein; D056465:Retinoblastoma-Binding Protein 1; D014157:Transcription Factors; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases