Simplified (partial) mechanism for the cytosolic stress response

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Simplified (partial) mechanism for the cytosolic stress response Simplified (partial) mechanism for the cytosolic stress response. Under stress conditions, native proteins and--to a larger degree--proteins containing missense sequence variations as well as modifications will be denatured. According to the simplified "chaperone sequestration" hypothesis, chaperones--particularly Hsp90 and Hsp70--leave the inactivated heat shock factor HSF1 and bind to the unfolded conformations. The unmasked HSF1 will trimerize and be transferred to the nucleus, where it is activated before binding to heat-shock elements of a number of heat-shock genes. Some of these genes code for chaperones, which try to compensate for the functional decrease in the amounts of chaperones available for protection of proteins against aggregation as well as against insults from misfolded proteins on vital cellular functions, such as the mitochondrial function. If this is compromised, reactive oxygen species (ROS) may be formed. In addition to the compensating stress response that induces the production of protecting chaperones, the proteasome--which is the most important proteolytic system in the cell--will try to eliminate misfolded and modified proteins. Depending on the balance between rate and amounts of unfolding and the compensating/eliminating mechanisms, the cell will survive or proceed into apoptosis. Source: Protein Folding and Misfolding: The Role of Cellular Protein Quality Control Systems in Inherited Disorders, The Online Metabolic and Molecular Bases of Inherited Disease Citation: Valle D, Beaudet AL, Vogelstein B, Kinzler KW, Antonarakis SE, Ballabio A, Gibson K, Mitchell G. The Online Metabolic and Molecular Bases of Inherited Disease; 2014 Available at: https://ommbid.mhmedical.com/DownloadImage.aspx?image=/data/books/971/ch13_1fg16.png&sec=62640652&BookID=971&ChapterSecID=62640472&imagename= Accessed: November 03, 2017 Copyright © 2017 McGraw-Hill Education. All rights reserved