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Effect of the Unfolded Protein Response on ER Protein Export: a Potential New Mechanism to Relieve ER Stress

Overview
Publisher Elsevier
Specialty Cell Biology
Date 2018 May 7
PMID 29730847
Citations 18
Authors
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Abstract

The unfolded protein response (UPR) is an adaptive cellular response that aims to relieve endoplasmic reticulum (ER) stress via several mechanisms, including inhibition of protein synthesis and enhancement of protein folding and degradation. There is a controversy over the effect of the UPR on ER protein export. While some investigators suggested that ER export is inhibited during ER stress, others suggested the opposite. In this article, their conflicting studies are analyzed and compared in attempt to solve this controversy. The UPR appears indeed to enhance ER export, possibly via multiple mechanisms. However, another factor, which is the integrity of the folding machinery/environment inside ER, determines whether ER export will appear increased or decreased during experimentation. Also, different methods of stress induction appear to have different effects on ER export. Thus, improvement of ER export may represent a new mechanism by which the UPR alleviates ER stress. This may help researchers to understand how the UPR works inside cells and how to manipulate it to alter cell fate during stress, either to promote cell survival or death. This may open up new approaches for the treatment of ER stress-related diseases.

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References
1.
Travers K, Patil C, Wodicka L, Lockhart D, Weissman J, Walter P . Functional and genomic analyses reveal an essential coordination between the unfolded protein response and ER-associated degradation. Cell. 2000; 101(3):249-58. DOI: 10.1016/s0092-8674(00)80835-1. View

2.
Bobrovnikova-Marjon E, Pytel D, Riese M, Vaites L, Singh N, Koretzky G . PERK utilizes intrinsic lipid kinase activity to generate phosphatidic acid, mediate Akt activation, and promote adipocyte differentiation. Mol Cell Biol. 2012; 32(12):2268-78. PMC: 3372262. DOI: 10.1128/MCB.00063-12. View

3.
Burikhanov R, Zhao Y, Goswami A, Qiu S, Schwarze S, Rangnekar V . The tumor suppressor Par-4 activates an extrinsic pathway for apoptosis. Cell. 2009; 138(2):377-88. PMC: 2774252. DOI: 10.1016/j.cell.2009.05.022. View

4.
Saito A, Hino S, Murakami T, Kanemoto S, Kondo S, Saitoh M . Regulation of endoplasmic reticulum stress response by a BBF2H7-mediated Sec23a pathway is essential for chondrogenesis. Nat Cell Biol. 2009; 11(10):1197-204. DOI: 10.1038/ncb1962. View

5.
DArcangelo J, Stahmer K, Miller E . Vesicle-mediated export from the ER: COPII coat function and regulation. Biochim Biophys Acta. 2013; 1833(11):2464-72. PMC: 3676692. DOI: 10.1016/j.bbamcr.2013.02.003. View