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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...

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Autores principales: Hiebel, Christof, Stürner, Elisabeth, Hoffmeister, Meike, Tascher, Georg, Schwarz, Mario, Nagel, Heike, Behrends, Christian, Münch, Christian, Behl, Christian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
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.
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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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