Dataset Information

Hatzimanikatis1999-Regulation of the G1-S transition of the mammalian cell cycle.

ABSTRACT: 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.

SUBMITTER: Ahmad Zyoud

PROVIDER: MODEL2005070001 | BioModels | 2020-05-07

REPOSITORIES: BioModels

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Publications

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

Hatzimanikatis V V Lee K H KH Bailey J E JE

Biotechnology and bioengineering 19991201 6

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. ...[more]

PMID: 10550769

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Project description:Barrack2014 - Calcium/cell cycle coupling - Rs dependent ATP release This model is designed based on the hypothesis that cytoplasmic calcium accelerates entry into S phase of the cell cycle and/or acts to recruit otherwise quiescents cells onto the cell cycle. The model describes the ATP mediated calcium-cell cycle coupling via Rs (retinoblastoma tumour suppressor protein bound to the E2F transcription factor) in a single radial glial cell. This model is described in the article: Modelling the coupling between intracellular calcium release and the cell cycle during cortical brain development. Barrack DS, Thul R, Owen MR. J Theor Biol. 2014 Jan 13;347C:17-32. Abstract: Most neocortical neurons formed during embryonic brain development arise from radial glial cells which communicate, in part, via ATP mediated calcium signals. Although the intercellular signalling mechanisms that regulate radial glia proliferation are not well understood, it has recently been demonstrated that ATP dependent intracellular calcium release leads to an increase of nearly 100% in overall cellular proliferation. It has been hypothesised that cytoplasmic calcium accelerates entry into S phase of the cell cycle and/or acts to recruit otherwise quiescent cells onto the cell cycle. In this paper we study this cell cycle acceleration and recruitment by forming a differential equation model for ATP mediated calcium-cell cycle coupling via Cyclin D in a single radial glial cell. Bifurcation analysis and numerical simulations suggest that the cell cycle period depends only weakly on cytoplasmic calcium. Therefore, the accelerative impact of calcium on the cell cycle can only account for a small fraction of the large increase in proliferation observed experimentally. Crucially however, our bifurcation analysis reveals that stable fixed point and stable limit cycle solutions can coexist, and that calcium dependent Cyclin D dynamics extend the oscillatory region to lower Cyclin D synthesis rates, thus rendering cells more susceptible to cycling. This supports the hypothesis that cycling glial cells recruit quiescent cells (in G0 phase) onto the cell cycle, via a calcium signalling mechanism, and that this may be the primary means by which calcium augments proliferation rates at the population scale. Numerical simulations of two coupled cells demonstrate that such a scenario is indeed feasible. This model is hosted on BioModels Database and identified by: BIOMD0000000509 . To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models . To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Dataset Information

Hatzimanikatis1999-Regulation of the G1-S transition of the mammalian cell cycle.

Publications

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

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