Sivery2016 - A mammalian heat shock response model

ABSTRACT: Environmental stress, such as oxidative or heat stress, induces the activation of the heat shock response(HSR) and leads to an increase in the heat shock proteins (HSPs) level. These HSPs act as molecularchaperones to maintain cellular proteostasis. Controlled by highly intricate regulatory mechanisms,having stress-induced activation and feedback regulations with multiple partners, the HSR is stillincompletely understood. In this context, we propose a minimal molecular model for the generegulatory network of the HSR that reproduces quantitatively different heat shock experiments bothon heat shock factor 1 (HSF1) and HSPs activities. This model, which is based on chemical kineticslaws, is kept with a low dimensionality without altering the biological interpretation of the modeldynamics. This simplistic model highlights the titration of HSF1 by chaperones as the guiding line ofthe network. Moreover, by a steady states analysis of the network, three different temperature stressregimes appear: normal, acute, and chronic, where normal stress corresponds to pseudo thermaladaption. The protein triage that governs the fate of damaged proteins or the different stress regimesare consequences of the titration mechanism. The simplicity of the present model is of interest inorder to study detailed modelling of cross regulation between the HSR and other major geneticnetworks like the cell cycle or the circadian clock.Sivéry, A., Courtade, E., Thommen, Q. (2016). A minimal titration model of the mammalian dynamical heat shock response. Physical biology, 13(6), 066008.

SUBMITTER: Quentin Thommen 

PROVIDER: MODEL2201210001 | biostudies-other |

SECONDARY ACCESSION(S): 27926536

REPOSITORIES: biostudies-other