Bcl-2-associated athanogene 3 (BAG3)

Bcl-2-associated athanogene 3 (BAG3) is a multifunctional co-chaperone protein that plays a pivotal role in cellular proteostasis and survival by regulating the activity of heat shock proteins, most notably Hsp70. It is distinguished by its conserved BAG domain, which mediates interaction with Hsp70, and other domains like the WW domain and IPV motifs that allow it to link molecular chaperones to the autophagic machinery and the cytoskeleton [UniProt: O95817]. In oncology, BAG3 is frequently overexpressed and serves as a pro-survival factor that protects cancer cells from apoptosis and stress-induced damage, making it a target for small-molecule inhibitors such as JG-98 [PubMed: 28243026]. Conversely, in the cardiovascular system, BAG3 is essential for maintaining the structural integrity of the sarcomere; mutations or decreased expression of BAG3 are primary drivers of dilated cardiomyopathy (DCM) and myofibrillar myopathy [PubMed: 21257401]. Consequently, therapeutic development for BAG3 spans from inhibition in cancer to gene replacement strategies in heart failure patients [PubMed: 31034449].

Other names

BAG family molecular chaperone regulator 3BCL2-binding athanogene 3BCL2-associated athanogene 3BISCAIR-1MFM6

BAG3 acts primarily as a co-chaperone for Hsp70, and drug mechanisms include small-molecule inhibition of the BAG3-Hsp70 protein-protein interaction to induce apoptosis in cancer cells, or gene therapy to restore BAG3 expression in failing cardiomyocytes [PubMed: 25611317, PubMed: 31034449].