A simple mass-action model for the eukaryotic heat shock response and its mathematical validation
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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.
KeywordsHeat shock response Heat shock protein Heat shock factor Heat shock element Mathematical model Validation Regulatory network
This work has been partially supported by the following grants from Academy of Finland: project 108421 (IP), project 203667 (A.Mizera), the Center of Excellence on Formal Methods in Programming (R-J.B.).
- Chen WW, Schorberl B, Jasper PJ, Niepel M, Nielsen UB, Lauffenburger DA, Sorger PK (2009) Input–output behavior of ErbB signaling pathways as revealed by a mass action model trained against dynamic data. Mol Syst Biol 5:1–19Google Scholar
- Guldberg CM, Waage P (1864) Studies concerning affinity. C. M. Forhandlinger: Videnskabs-Selskabet i Christiana 35Google Scholar
- Kline MP, Morimoto RI (1997) Repression of the heat shock factor 1 transcriptional activation domain is modulated by constitutive phosphorylation. Mol Cell Biol 17(4):2107–2115Google Scholar
- McKay MD, Beckman RJ, Conover WJ (1979) A comparison of three methods for selecting values of input variables in the analysis of output from a computer code. Technometrics 21(2):239-245Google Scholar
- Morimoto RI, Jurivich DA, Kroger PE, Mathur SK, Murphy SP, et al (1994) Regulation of heat shock gene transcription by a family of heat shock factors. In: Morimoto RI, Tissières A, Georgopoulos C (eds) The biology of the heat shock proteins and molecular chaperones. Cold Spring Harbor Laboratory, New York, pp. 417–455Google Scholar
- Petre I, Mizera A, Hyder CL, Mikhailov A, Eriksson JE, Sistonen L, Back R-J (2009) A new mathematical model for the heat shock response. In: Condon A, Harel D, Kok J, Salomaa A (eds) Algorithmic bioprocesses. Springer, New York, pp. 411–428Google Scholar
- Voellmy R (1994) Transduction of the stress signal and mechanisms of transcriptional regulation of heat shock/stress protein gene expression in higher eukaryotes. Crit Rev Eukaryot Gene Expr 4:357–401Google Scholar