Mechanisms, regulation and functions of the unfolded protein response
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2020Metadata
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Hetz Flores, Claudio
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Mechanisms, regulation and functions of the unfolded protein response
Abstract
The unfolded protein response (UPR) comprises a network of signalling pathways that reprogramme transcription, translation and protein modifications to relieve the load of unfolded or misfolded proteins in the endoplasmic reticulum lumen and restore proteostasis. Understanding the regulation of the UPR and the role it has in the pathophysiology of various cell types and organs might open new therapeutic avenues.
Cellular stress induced by the abnormal accumulation of unfolded or misfolded proteins at the endoplasmic reticulum (ER) is emerging as a possible driver of human diseases, including cancer, diabetes, obesity and neurodegeneration. ER proteostasis surveillance is mediated by the unfolded protein response (UPR), a signal transduction pathway that senses the fidelity of protein folding in the ER lumen. The UPR transmits information about protein folding status to the nucleus and cytosol to adjust the protein folding capacity of the cell or, in the event of chronic damage, induce apoptotic cell death. Recent advances in the understanding of the regulation of UPR signalling and its implications in the pathophysiology of disease might open new therapeutic avenues.
Patrocinador
United States Department of Health & Human Services
National Institutes of Health (NIH) - USA
NIH National Cancer Institute (NCI)
R01 CA198103
P30 CA030199
United States Department of Health & Human Services
National Institutes of Health (NIH) - USA
NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK)
R01 DK103185
R01 DK113171
P30 DK063491
R24 DK110973
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Artículo de publicación ISI Artículo de publicación SCOPUS
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Nature Reviews Molecular Cell Biology 21(8):1-18
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