Cargando…

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 (...

Descripción completa

Detalles Bibliográficos
Autores principales: Féral, Kelly, Jaud, Manon, Philippe, Céline, Di Bella, Doriana, Pyronnet, Stéphane, Rouault-Pierre, Kevin, Mazzolini, Laurent, Touriol, Christian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
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
_version_ 1783656446002462720
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
work_keys_str_mv AT feralkelly erstressandunfoldedproteinresponseinleukemiafriendfoeorboth
AT jaudmanon erstressandunfoldedproteinresponseinleukemiafriendfoeorboth
AT philippeceline erstressandunfoldedproteinresponseinleukemiafriendfoeorboth
AT dibelladoriana erstressandunfoldedproteinresponseinleukemiafriendfoeorboth
AT pyronnetstephane erstressandunfoldedproteinresponseinleukemiafriendfoeorboth
AT rouaultpierrekevin erstressandunfoldedproteinresponseinleukemiafriendfoeorboth
AT mazzolinilaurent erstressandunfoldedproteinresponseinleukemiafriendfoeorboth
AT touriolchristian erstressandunfoldedproteinresponseinleukemiafriendfoeorboth