The Unfolded Protein Response: From Stress Pathway to Homeostatic Regulation
Abstract
The vast majority of proteins that a cell secretes or displays on its surface first enter the endoplasmic reticulum (ER), where they fold and assemble. Only properly assembled proteins advance from the ER to the cell surface. To ascertain fidelity in protein folding, cells regulate the protein-folding capacity in the ER according to need. The ER responds to the burden of unfolded proteins in its lumen (ER stress) by activating intracellular signal transduction pathways, collectively termed the unfolded protein response (UPR). Together, at least three mechanistically distinct branches of the UPR regulate the expression of numerous genes that maintain homeostasis in the ER or induce apoptosis if ER stress remains unmitigated. Recent advances shed light on mechanistic complexities and on the role of the UPR in numerous diseases.
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Published In
Science
Volume 334 | Issue 6059
25 November 2011
25 November 2011
Copyright
Copyright © 2011, American Association for the Advancement of Science.
Submission history
Published in print: 25 November 2011
Acknowledgments
We thank A. Korrenykh, A. Göke, and members of the Walter lab for helpful comments on the manuscript; K. Gotthardt for help in preparing the structural models; and D. Pincus and H. Li for contributing the fluorescence micrographs in Fig. 3. Supported by funds from the Howard Hughes Medical Institute and the Wellcome Trust. P.W. is an Investigator of the Howard Hughes Medical Institute and D.R. is a Principal Research Fellow of the Wellcome Trust.
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