The Unfolded Protein Response: An Overview

Read, Adam; Schröder, Martin

Abstract

The unfolded protein response is the mechanism by which cells control endoplasmic reticulum (ER) protein homeostasis. Under normal conditions, the UPR is not activated; however, under certain stresses, such as hypoxia or altered glycosylation, the UPR can be activated due to an accumulation of unfolded proteins. The activation of the UPR involves three signaling pathways, IRE1, PERK and ATF6, which all play vital roles in returning protein homeostasis to levels seen in non-stressed cells. IRE1 is the best studied of the three pathways, as it is the only pathway present in Saccharomyces cerevisiae. This pathway involves spliceosome independent splicing of HAC1 or XBP1 in yeast and mammalians cells, respectively. PERK limits protein synthesis, therefore reducing the number of new proteins requiring folding. ATF6 is translocated and proteolytically cleaved, releasing a NH2 domain fragment which is transported to the nucleus and which affects gene expression. If the UPR is unsuccessful at reducing the load of unfolded proteins in the ER and the UPR signals remain activated, this can lead to programmed cell death.

Citation

Read, A., & Schröder, M. (2021). The Unfolded Protein Response: An Overview. Biology, 10(5), Article 384. https://doi.org/10.3390/biology10050384

• Journal Article Type: Article
• Acceptance Date: Apr 27, 2021
• Online Publication Date: Apr 29, 2021
• Publication Date: 2021-05
• Deposit Date: Oct 20, 2021
• Publicly Available Date: Oct 28, 2022
• Journal: Biology
• Electronic ISSN: 2079-7737
• Publisher: MDPI
• Peer Reviewed: Peer Reviewed
• Volume: 10
• Issue: 5
• Article Number: 384
• DOI: https://doi.org/10.3390/biology10050384
• Public URL: https://durham-repository.worktribe.com/output/1229002