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. Author manuscript; available in PMC: 2012 Dec 29.
Published in final edited form as: J Cereb Blood Flow Metab. 2006 Aug 16;27(5):875–893. doi: 10.1038/sj.jcbfm.9600388

Figure 3.

Figure 3

The HSR and UPR as examples of endogenous cellular stress systems typical of the model in Figure 2. Accumulation of denatured or misfolded proteins in the cytoplasm or ER, activate the HSR and UPR, respectively. HSF and ATF6 and XBP-1 are the transcriptional effectors for the HSR and UPR, respectively. Both the HSR and the UPR lead to transient inhibition of protein synthesis initiated by at least transient phosphorylation of eIF2α. Both systems lead to increased translation of stress-induced mRNAs. These mRNAs escape translation arrest and lead to production of stress proteins. Heat shock proteins catalyze proper protein folding and prevent protein aggregation, thereby abating cell damage. Heat shock proteins also dissolve stress granules, leading to recovery of protein synthesis. Upregulation of ER enzymes and chaperones increase the processing capacity of the ER lumen, thereby abating ER damage. Translation of GADD34 during the UPR catalyzes dephosphorylation of eIF2α(P), allowing recovery of general protein synthesis.