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BAG3 Proteomic Signature under Proteostasis Stress
The multifunctional HSP70 co-chaperone BAG3 (BCL-2-associated athanogene 3) represents a key player in the quality control of the cellular proteostasis network. In response to stress, BAG3 specifically targets aggregation-prone proteins to the perinuclear aggresome and promotes their degradation via...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7694386/ https://www.ncbi.nlm.nih.gov/pubmed/33158300 http://dx.doi.org/10.3390/cells9112416 |
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author | Hiebel, Christof Stürner, Elisabeth Hoffmeister, Meike Tascher, Georg Schwarz, Mario Nagel, Heike Behrends, Christian Münch, Christian Behl, Christian |
author_facet | Hiebel, Christof Stürner, Elisabeth Hoffmeister, Meike Tascher, Georg Schwarz, Mario Nagel, Heike Behrends, Christian Münch, Christian Behl, Christian |
author_sort | Hiebel, Christof |
collection | PubMed |
description | The multifunctional HSP70 co-chaperone BAG3 (BCL-2-associated athanogene 3) represents a key player in the quality control of the cellular proteostasis network. In response to stress, BAG3 specifically targets aggregation-prone proteins to the perinuclear aggresome and promotes their degradation via BAG3-mediated selective macroautophagy. To adapt cellular homeostasis to stress, BAG3 modulates and functions in various cellular processes and signaling pathways. Noteworthy, dysfunction and deregulation of BAG3 and its pathway are pathophysiologically linked to myopathies, cancer, and neurodegenerative disorders. Here, we report a BAG3 proteomic signature under proteostasis stress. To elucidate the dynamic and multifunctional action of BAG3 in response to stress, we established BAG3 interactomes under basal and proteostasis stress conditions by employing affinity purification combined with quantitative mass spectrometry. In addition to the identification of novel potential BAG3 interactors, we defined proteins whose interaction with BAG3 was altered upon stress. By functional annotation and protein-protein interaction enrichment analysis of the identified potential BAG3 interactors, we confirmed the multifunctionality of BAG3 and highlighted its crucial role in diverse cellular signaling pathways and processes, ensuring cellular proteostasis and cell viability. These include protein folding and degradation, gene expression, cytoskeleton dynamics (including cell cycle and transport), as well as granulostasis, in particular. |
format | Online Article Text |
id | pubmed-7694386 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-76943862020-11-28 BAG3 Proteomic Signature under Proteostasis Stress Hiebel, Christof Stürner, Elisabeth Hoffmeister, Meike Tascher, Georg Schwarz, Mario Nagel, Heike Behrends, Christian Münch, Christian Behl, Christian Cells Article The multifunctional HSP70 co-chaperone BAG3 (BCL-2-associated athanogene 3) represents a key player in the quality control of the cellular proteostasis network. In response to stress, BAG3 specifically targets aggregation-prone proteins to the perinuclear aggresome and promotes their degradation via BAG3-mediated selective macroautophagy. To adapt cellular homeostasis to stress, BAG3 modulates and functions in various cellular processes and signaling pathways. Noteworthy, dysfunction and deregulation of BAG3 and its pathway are pathophysiologically linked to myopathies, cancer, and neurodegenerative disorders. Here, we report a BAG3 proteomic signature under proteostasis stress. To elucidate the dynamic and multifunctional action of BAG3 in response to stress, we established BAG3 interactomes under basal and proteostasis stress conditions by employing affinity purification combined with quantitative mass spectrometry. In addition to the identification of novel potential BAG3 interactors, we defined proteins whose interaction with BAG3 was altered upon stress. By functional annotation and protein-protein interaction enrichment analysis of the identified potential BAG3 interactors, we confirmed the multifunctionality of BAG3 and highlighted its crucial role in diverse cellular signaling pathways and processes, ensuring cellular proteostasis and cell viability. These include protein folding and degradation, gene expression, cytoskeleton dynamics (including cell cycle and transport), as well as granulostasis, in particular. MDPI 2020-11-04 /pmc/articles/PMC7694386/ /pubmed/33158300 http://dx.doi.org/10.3390/cells9112416 Text en © 2020 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 | Article Hiebel, Christof Stürner, Elisabeth Hoffmeister, Meike Tascher, Georg Schwarz, Mario Nagel, Heike Behrends, Christian Münch, Christian Behl, Christian BAG3 Proteomic Signature under Proteostasis Stress |
title | BAG3 Proteomic Signature under Proteostasis Stress |
title_full | BAG3 Proteomic Signature under Proteostasis Stress |
title_fullStr | BAG3 Proteomic Signature under Proteostasis Stress |
title_full_unstemmed | BAG3 Proteomic Signature under Proteostasis Stress |
title_short | BAG3 Proteomic Signature under Proteostasis Stress |
title_sort | bag3 proteomic signature under proteostasis stress |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7694386/ https://www.ncbi.nlm.nih.gov/pubmed/33158300 http://dx.doi.org/10.3390/cells9112416 |
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