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Swat2004_Mammalian_G1_S_Transition

ABSTRACT: This is the extended model described the article: Bifurcation analysis of the regulatory modules of the mammalian G1/S transition. Swat M, Kel A, Herzel H. Bioinformatics 2004 Jul 10;20(10):1506-11. PMID: 15231543 , doi: 10.1093/bioinformatics/bth110 Abstract: MOTIVATION: Mathematical models of the cell cycle can contribute to an understanding of its basic mechanisms. Modern simulation tools make the analysis of key components and their interactions very effective. This paper focuses on the role of small modules and feedbacks in the gene-protein network governing the G1/S transition in mammalian cells. Mutations in this network may lead to uncontrolled cell proliferation. Bifurcation analysis helps to identify the key components of this extremely complex interaction network. RESULTS: We identify various positive and negative feedback loops in the network controlling the G1/S transition. It is shown that the positive feedback regulation of E2F1 and a double activator-inhibitor module can lead to bistability. Extensions of the core module preserve the essential features such as bistability. The complete model exhibits a transcritical bifurcation in addition to bistability. We relate these bifurcations to the cell cycle checkpoint and the G1/S phase transition point. Thus, core modules can explain major features of the complex G1/S network and have a robust decision taking function. This model originates from BioModels Database: A Database of Annotated Published Models. It is copyright (c) 2005-2010 The BioModels Team. 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. In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not.. To cite BioModels Database, please use Le Novère N., Bornstein B., Broicher A., Courtot M., Donizelli M., Dharuri H., Li L., Sauro H., Schilstra M., Shapiro B., Snoep J.L., Hucka M. (2006) BioModels Database: A Free, Centralized Database of Curated, Published, Quantitative Kinetic Models of Biochemical and Cellular Systems Nucleic Acids Res., 34: D689-D691.

SUBMITTER: Nicolas Le Novère

PROVIDER: BIOMD0000000228 | BioModels | 2024-09-02

REPOSITORIES: BioModels

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Bifurcation analysis of the regulatory modules of the mammalian G1/S transition.

Swat Maciej M Kel Alexander A Herzel Hanspeter H

Bioinformatics (Oxford, England) 20040701 10

<h4>Motivation</h4>Mathematical models of the cell cycle can contribute to an understanding of its basic mechanisms. Modern simulation tools make the analysis of key components and their interactions very effective. This paper focuses on the role of small modules and feedbacks in the gene-protein network governing the G1/S transition in mammalian cells. Mutations in this network may lead to uncontrolled cell proliferation. Bifurcation analysis helps to identify the key components of this extreme ...[more]

PMID: 15231543

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