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 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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Author:Christof Hiebel, Elisabeth Stürner, Meike HoffmeisterORCiDGND, Georg TascherORCiDGND, Mario Schwarz, Heike Nagel, Christian Behrends, Christian MünchORCiD, Christian Behl
Pubmed Id:
Parent Title (English):Cells
Place of publication:Basel
Document Type:Article
Date of Publication (online):2020/11/04
Date of first Publication:2020/11/04
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2020/12/23
Tag:BAG3; autophagy; interactome; protein quality control; proteostasis; stress response
Issue:Article 2416
Page Number:40
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0