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Unfolding the Role of Large Heat Shock Proteins: New Insights and Therapeutic Implications
Heat shock proteins (HSPs) of eukaryotes are evolutionarily conserved molecules present in all the major intracellular organelles. They mainly function as molecular chaperones and participate in maintenance of protein homeostasis in physiological state and under stressful conditions. Despite their r...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2016
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4771732/ https://www.ncbi.nlm.nih.gov/pubmed/26973652 http://dx.doi.org/10.3389/fimmu.2016.00075 |
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author | Zuo, Daming Subjeck, John Wang, Xiang-Yang |
author_facet | Zuo, Daming Subjeck, John Wang, Xiang-Yang |
author_sort | Zuo, Daming |
collection | PubMed |
description | Heat shock proteins (HSPs) of eukaryotes are evolutionarily conserved molecules present in all the major intracellular organelles. They mainly function as molecular chaperones and participate in maintenance of protein homeostasis in physiological state and under stressful conditions. Despite their relative abundance, the large HSPs, i.e., Hsp110 and glucose-regulated protein 170 (Grp170), have received less attention compared to other conventional HSPs. These proteins are distantly related to the Hsp70 and belong to Hsp70 superfamily. Increased sizes of Hsp110 and Grp170, due to the presence of a loop structure, result in their exceptional capability in binding to polypeptide substrates or non-protein ligands, such as pathogen-associated molecules. These interactions that occur in the extracellular environment during tissue injury or microbial infection may lead to amplification of an immune response engaging both innate and adaptive immune components. Here, we review the current advances in understanding these large HSPs as molecular chaperones in proteostasis control and immune modulation as well as their therapeutic implications in treatment of cancer and neurodegeneration. Given their unique immunoregulatory activities, we also discuss the emerging evidence of their potential involvement in inflammatory and immune-related diseases. |
format | Online Article Text |
id | pubmed-4771732 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-47717322016-03-11 Unfolding the Role of Large Heat Shock Proteins: New Insights and Therapeutic Implications Zuo, Daming Subjeck, John Wang, Xiang-Yang Front Immunol Immunology Heat shock proteins (HSPs) of eukaryotes are evolutionarily conserved molecules present in all the major intracellular organelles. They mainly function as molecular chaperones and participate in maintenance of protein homeostasis in physiological state and under stressful conditions. Despite their relative abundance, the large HSPs, i.e., Hsp110 and glucose-regulated protein 170 (Grp170), have received less attention compared to other conventional HSPs. These proteins are distantly related to the Hsp70 and belong to Hsp70 superfamily. Increased sizes of Hsp110 and Grp170, due to the presence of a loop structure, result in their exceptional capability in binding to polypeptide substrates or non-protein ligands, such as pathogen-associated molecules. These interactions that occur in the extracellular environment during tissue injury or microbial infection may lead to amplification of an immune response engaging both innate and adaptive immune components. Here, we review the current advances in understanding these large HSPs as molecular chaperones in proteostasis control and immune modulation as well as their therapeutic implications in treatment of cancer and neurodegeneration. Given their unique immunoregulatory activities, we also discuss the emerging evidence of their potential involvement in inflammatory and immune-related diseases. Frontiers Media S.A. 2016-03-01 /pmc/articles/PMC4771732/ /pubmed/26973652 http://dx.doi.org/10.3389/fimmu.2016.00075 Text en Copyright © 2016 Zuo, Subjeck and Wang. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Zuo, Daming Subjeck, John Wang, Xiang-Yang Unfolding the Role of Large Heat Shock Proteins: New Insights and Therapeutic Implications |
title | Unfolding the Role of Large Heat Shock Proteins: New Insights and Therapeutic Implications |
title_full | Unfolding the Role of Large Heat Shock Proteins: New Insights and Therapeutic Implications |
title_fullStr | Unfolding the Role of Large Heat Shock Proteins: New Insights and Therapeutic Implications |
title_full_unstemmed | Unfolding the Role of Large Heat Shock Proteins: New Insights and Therapeutic Implications |
title_short | Unfolding the Role of Large Heat Shock Proteins: New Insights and Therapeutic Implications |
title_sort | unfolding the role of large heat shock proteins: new insights and therapeutic implications |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4771732/ https://www.ncbi.nlm.nih.gov/pubmed/26973652 http://dx.doi.org/10.3389/fimmu.2016.00075 |
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