The role of BAG3 in health and disease: A "Magic BAG of Tricks"

J Cell Biochem. 2022 Jan;123(1):4-21. doi: 10.1002/jcb.29952. Epub 2021 May 14.

Abstract

The multi-domain structure of Bcl-2-associated athanogene 3 (BAG3) facilitates its interaction with many different proteins that participate in regulating a variety of biological pathways. After revisiting the BAG3 literature published over the past ten years with Citespace software, we classified the BAG3 research into several clusters, including cancer, cardiomyopathy, neurodegeneration, and viral propagation. We then highlighted recent key findings in each cluster. To gain greater insight into the roles of BAG3, we analyzed five different published mass spectrometry data sets of proteins that co-immunoprecipitate with BAG3. These data gave us insight into universal, as well as cell-type-specific BAG3 interactors in cancer cells, cardiomyocytes, and neurons. Finally, we mapped variable BAG3 SNPs and also mutation data from previous publications to further explore the link between the domains and function of BAG3. We believe this review will provide a better understanding of BAG3 and direct future studies towards understanding BAG3 function in physiological and pathological conditions.

Keywords: BAG3; cancer; interactome; myopathy; neurodegeneration; viral replication.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Apoptosis Regulatory Proteins / genetics*
  • Apoptosis Regulatory Proteins / metabolism*
  • Cardiomyopathies / metabolism*
  • Humans
  • Mutation
  • Myocytes, Cardiac / metabolism
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Neurodegenerative Diseases / metabolism*
  • Neurons / metabolism
  • Polymorphism, Single Nucleotide
  • Virus Diseases / metabolism*
  • Virus Diseases / virology

Substances

  • Adaptor Proteins, Signal Transducing
  • Apoptosis Regulatory Proteins
  • BAG3 protein, human