A simple mass-action model for the eukaryotic heat shock response and its mathematical validation

Authors:
Ion Petre;Andrzej Mizera;Claire L. Hyder;Annika Meinander;Andrey Mikhailov;Richard I. Morimoto;Lea Sistonen;John E. Eriksson;Ralph-Johan Back
Affiliations:
Department of Information Technologies, Åbo Akademi University, Turku, Finland 20520;Department of Information Technologies, Åbo Akademi University, Turku, Finland 20520;Turku Centre for Biotechnology, Turku, Finland and Department of Biosciences, Åbo Akademi University, Turku, Finland 20520;Turku Centre for Biotechnology, Turku, Finland and Department of Biosciences, Åbo Akademi University, Turku, Finland 20520;Turku Centre for Biotechnology, Turku, Finland and Department of Biosciences, Åbo Akademi University, Turku, Finland 20520;Department of Biochemistry, Molecular Biology and Cell Biology, Rice Institute for Biomedical Research, Northwestern University, Evanston, USA 60208;Turku Centre for Biotechnology, Turku, Finland and Department of Biosciences, Åbo Akademi University, Turku, Finland 20520;Turku Centre for Biotechnology, Turku, Finland and Department of Biosciences, Åbo Akademi University, Turku, Finland 20520;Department of Information Technologies, Åbo Akademi University, Turku, Finland 20520
Venue:
Natural Computing: an international journal
Year:
2011

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Abstract

The heat shock response is a primordial defense mechanism against cell stress and protein misfolding. It proceeds with the minimum number of mechanisms that any regulatory network must include, a stress-induced activation and a feedback regulation, and can thus be regarded as the archetype for a cellular regulatory process. We propose here a simple mechanistic model for the eukaryotic heat shock response, including its mathematical validation. Based on numerical predictions of the model and on its sensitivity analysis, we minimize the model by identifying the reactions with marginal contribution to the heat shock response. As the heat shock response is a very basic and conserved regulatory network, our analysis of the network provides a useful foundation for modeling strategies of more complex cellular processes.