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

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.

BAG3 Alleviates Atherosclerosis by Inhibiting Endothelial-to-Mesenchymal Transition via Autophagy Activation

“…Human BAG3 is 575 amino acids in length and has a molecular mass of 74 kDa [ 32 ], mainly seen in the cytoplasm [ 33 ]. Previous studies have indicated that BAG3 is involved in various cardiovascular diseases, such as myocardial hypertrophy, dilated cardiomyopathy, and chronic heart failure.…”

Genetic Insights into Primary Restrictive Cardiomyopathy

“…BAG3 is a co-chaperone binding to the ATPase domain of heat shock protein Hsc70/Hsp70 and regulating its chaperone function [209]. BAG3 is structurally organized in an Nterminal tryptophan-tryptophan (WW) domain, two IPV domains, two 14-3-3 binding motifs, a proline-rich region and a C-terminal BAG domain [210,211]. The protein-protein interaction of BAG3 with Hsc70/Hsp70 is mediated by its BAG domain [212].…”

Genetic Insights Into Primary Restrictive Cardiomyopathy

“…BAG3 is a co-chaperone binding to the ATPase domain of heat shock protein Hsc70/Hsp70 and regulating its chaperone function [200]. BAG3 is structurally organized in a N-terminal tryptophan-tryptophan (WW) domain, two IPV domains, two 14-3-3 binding motifs, a proline-rich region and a C-terminal BAG domain [201,202]. The protein-protein interaction of BAG3 with Hsc70/Hsp70 is mediated by its BAG domain [203].…”