Activation of Hsf1p secondarily induces the expression of chaperonins and inhibits the cell cycle. A mathematical model of these aspects is found in this reference [41]. In order to model Hsf1p activation, we consider a pool of yeast proteins that is prone to heat denaturation and serves the purpose of providing the signal input to the heat

stress response (Figure 1). These proteins might be enzymes or structural Inhibitors,research,lifescience,medical proteins that tend to unfold at non-optimal temperatures, or they might be intrinsically disordered proteins that are known to have signaling functions [42]. These types of heat-induced effects can be converted into Inhibitors,research,lifescience,medical a canonical model where a folded protein controls a heat signaling pathway and where its unfolding triggers—or at least contributes

to—a stress response. As is typical in nature, the ultimate response to a stress situation is the result of a balance between opposing forces. We already discussed the counteracting effects of cAMP-PKA and heat on the localization of MSN2/4 (Figure 2). Another example of the balance of opposing forces Inhibitors,research,lifescience,medical is the folding, unfolding, and refolding dynamics of proteins (Figure 3). The disaccharide trehalose protects proteins from unfolding, but interferes with the refolding and degradation of the unfolded Inhibitors,research,lifescience,medical protein [43]. By contrast, chaperonins (as representatives of heat shock proteins) promote refolding and facilitate the degradation of unfolded proteins. If these forces are entered into a model, the degradation of unfolded forms has to be balanced with the production of proteins, so that the model may eventually reach a steady state. This production term may be made heat stress sensitive, Inhibitors,research,lifescience,medical which is in line with the observation that many transcripts are simply

down-regulated under heat stress [5]. At the same time, protein degradation is known to be affected by heat, and inclusion of this effect in the model might improve the functioning of this hypothetical signaling pathway under stress. 3.5. Modeling Specific Metabolic Events under Heat Stress: The Trehalose AV-951 Cycle Events at the metabolic level are typically easier to model than at other levels, because specific kinetic information is often available and phenomena like the conservation of mass in reactions provide very valuable constraints that aid the parameter estimation process. As a consequence, several models have been proposed to Enzastaurin clinical analyze heat stress and its metabolic effects in yeast and other organisms (e.g., [44,45,46,47,48,49,50,51]). For example, Voit and prompt delivery Radivoyevitch [48] used a canonical modeling approach to study the metabolic consequences of changes in gene expression following heat stress.