A mathematical description of regulation of the G1-S transition of the mammalian cell cycle

A math. model of regulation of the G1-S transition of the mammalian cell cycle has been formulated to organize available exptl. mol.-level information in a systematic quant. framework and to evaluate the ability of this manifestation of current knowledge to calc. correctly exptl. obsd. 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 solns. corresponding to cell proliferation and asymptotically stable solns. corresponding to cell cycle arrest (quiescence). Bifurcation anal. of the system suggests changes in the intracellular concns. of either E2F or cyclin E can activate cell proliferation and that co-overexpression of these mols. can prevent cell proliferation. Further anal. suggests that the amt. of inhibitor necessary to prevent cell proliferation is independent of the concns. of cyclin E and E2F and depends only on the equil. ratio between the bound and unbound forms of the inhibitor to the complex. [on SciFinder (R)]