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The Phosphorylation of the Heat Shock Factor as a Modulator for the Heat Shock Response

Eugen Czeizler, Vladimir Rogojin, Ion Petre, The Phosphorylation of the Heat Shock Factor as a Modulator for the Heat Shock Response. In: F. Fages (Ed.), Proceedings of the 9th International Conference on Computational Methods in Systems Biology, 9-24, ACM, 2011.

Abstract:

The heat shock response is a well conserved defence mechanism
against the accumulation of misfolded proteins due to
prolonged elevated heat. The cell responds to heat shock by
raising the levels of heat shock proteins (hsp), which are responsible
for chaperoning protein refolding. The synthesis of
hsp is highly regulated at the transcription level by specific
heat shock (transcription) factors (hsf). One of the regulation
mechanisms is the phosphorylation of hsf’s. Experimental
evidence shows a connection between the hyper-phosphorylation
of hsf’s and the transactivation of the hsp-encoding
genes. In this paper we incorporate several (de)phosphorylation
pathways into an existing well validated computational
model of the heat shock response. We analyze the
quantitative control of each of these pathways over the entire
process. For each of these pathways we create detailed
computational models which we subject to parameter estimation
in order to fit them to existing experimental data.
In particular, we find conclusive evidence supporting only
one of the analyzed pathways. Also, we corroborate our results
with a sequent set of computational models, of a more
reduced size.

BibTeX entry:

@INPROCEEDINGS{inpCzRoPe11a,
  title = {The Phosphorylation of the Heat Shock Factor as a Modulator for the Heat Shock Response},
  booktitle = {Proceedings of the 9th International Conference on Computational Methods in Systems Biology},
  author = {Czeizler, Eugen and Rogojin, Vladimir and Petre, Ion},
  editor = {Fages, F.},
  publisher = {ACM},
  pages = {9-24},
  year = {2011},
  keywords = {Simulation and Modeling— General, Simulation Theory, Applications, Model Validation and Analysis, Model Development},
}

Belongs to TUCS Research Unit(s): Computational Biomodeling Laboratory (Combio Lab)

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