BAG3 Proteomic Signature under Proteostasis Stress

Cells. 2020 Nov 4;9(11):2416. doi: 10.3390/cells9112416.


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.

Keywords: BAG3; autophagy; interactome; protein quality control; proteostasis; stress response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Apoptosis Regulatory Proteins / metabolism*
  • Gene Ontology
  • HEK293 Cells
  • Humans
  • Molecular Sequence Annotation
  • Multivariate Analysis
  • Proteasome Inhibitors / pharmacology
  • Protein Binding / drug effects
  • Protein Interaction Maps / drug effects
  • Proteomics*
  • Proteostasis* / drug effects
  • Proto-Oncogene Proteins c-yes / metabolism
  • Stress, Physiological* / drug effects


  • Adaptor Proteins, Signal Transducing
  • Apoptosis Regulatory Proteins
  • BAG3 protein, human
  • Proteasome Inhibitors
  • Proto-Oncogene Proteins c-yes
  • YES1 protein, human