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ER Stress and Unfolded Protein Response in Leukemia: Friend, Foe, or Both?
The unfolded protein response (UPR) is an evolutionarily conserved adaptive signaling pathway triggered by a stress of the endoplasmic reticulum (ER) lumen compartment, which is initiated by the accumulation of unfolded proteins. This response, mediated by three sensors-Inositol Requiring Enzyme 1 (...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7911881/ https://www.ncbi.nlm.nih.gov/pubmed/33573353 http://dx.doi.org/10.3390/biom11020199 |
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author | Féral, Kelly Jaud, Manon Philippe, Céline Di Bella, Doriana Pyronnet, Stéphane Rouault-Pierre, Kevin Mazzolini, Laurent Touriol, Christian |
author_facet | Féral, Kelly Jaud, Manon Philippe, Céline Di Bella, Doriana Pyronnet, Stéphane Rouault-Pierre, Kevin Mazzolini, Laurent Touriol, Christian |
author_sort | Féral, Kelly |
collection | PubMed |
description | The unfolded protein response (UPR) is an evolutionarily conserved adaptive signaling pathway triggered by a stress of the endoplasmic reticulum (ER) lumen compartment, which is initiated by the accumulation of unfolded proteins. This response, mediated by three sensors-Inositol Requiring Enzyme 1 (IRE1), Activating Transcription Factor 6 (ATF6), and Protein Kinase RNA-Like Endoplasmic Reticulum Kinase (PERK)—allows restoring protein homeostasis and maintaining cell survival. UPR represents a major cytoprotective signaling network for cancer cells, which frequently experience disturbed proteostasis owing to their rapid proliferation in an usually unfavorable microenvironment. Increased basal UPR also participates in the resistance of tumor cells against chemotherapy. UPR activation also occurs during hematopoiesis, and growing evidence supports the critical cytoprotective role played by ER stress in the emergence and proliferation of leukemic cells. In case of severe or prolonged stress, pro-survival UPR may however evolve into a cell death program called terminal UPR. Interestingly, a large number of studies have revealed that the induction of proapoptotic UPR can also strongly contribute to the sensitization of leukemic cells to chemotherapy. Here, we review the current knowledge on the consequences of the deregulation of UPR signaling in leukemias and their implications for the treatment of these diseases. |
format | Online Article Text |
id | pubmed-7911881 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-79118812021-02-28 ER Stress and Unfolded Protein Response in Leukemia: Friend, Foe, or Both? Féral, Kelly Jaud, Manon Philippe, Céline Di Bella, Doriana Pyronnet, Stéphane Rouault-Pierre, Kevin Mazzolini, Laurent Touriol, Christian Biomolecules Review The unfolded protein response (UPR) is an evolutionarily conserved adaptive signaling pathway triggered by a stress of the endoplasmic reticulum (ER) lumen compartment, which is initiated by the accumulation of unfolded proteins. This response, mediated by three sensors-Inositol Requiring Enzyme 1 (IRE1), Activating Transcription Factor 6 (ATF6), and Protein Kinase RNA-Like Endoplasmic Reticulum Kinase (PERK)—allows restoring protein homeostasis and maintaining cell survival. UPR represents a major cytoprotective signaling network for cancer cells, which frequently experience disturbed proteostasis owing to their rapid proliferation in an usually unfavorable microenvironment. Increased basal UPR also participates in the resistance of tumor cells against chemotherapy. UPR activation also occurs during hematopoiesis, and growing evidence supports the critical cytoprotective role played by ER stress in the emergence and proliferation of leukemic cells. In case of severe or prolonged stress, pro-survival UPR may however evolve into a cell death program called terminal UPR. Interestingly, a large number of studies have revealed that the induction of proapoptotic UPR can also strongly contribute to the sensitization of leukemic cells to chemotherapy. Here, we review the current knowledge on the consequences of the deregulation of UPR signaling in leukemias and their implications for the treatment of these diseases. MDPI 2021-01-30 /pmc/articles/PMC7911881/ /pubmed/33573353 http://dx.doi.org/10.3390/biom11020199 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Féral, Kelly Jaud, Manon Philippe, Céline Di Bella, Doriana Pyronnet, Stéphane Rouault-Pierre, Kevin Mazzolini, Laurent Touriol, Christian ER Stress and Unfolded Protein Response in Leukemia: Friend, Foe, or Both? |
title | ER Stress and Unfolded Protein Response in Leukemia: Friend, Foe, or Both? |
title_full | ER Stress and Unfolded Protein Response in Leukemia: Friend, Foe, or Both? |
title_fullStr | ER Stress and Unfolded Protein Response in Leukemia: Friend, Foe, or Both? |
title_full_unstemmed | ER Stress and Unfolded Protein Response in Leukemia: Friend, Foe, or Both? |
title_short | ER Stress and Unfolded Protein Response in Leukemia: Friend, Foe, or Both? |
title_sort | er stress and unfolded protein response in leukemia: friend, foe, or both? |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7911881/ https://www.ncbi.nlm.nih.gov/pubmed/33573353 http://dx.doi.org/10.3390/biom11020199 |
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