Breaking BAG: The Co-Chaperone BAG3 in Health and Disease

Human BAG (Bcl-2-associated athanogene) proteins form a family of antiapoptotic proteins that currently consists of six members (BAG1–6) all sharing the BAG protein domain from which the name arises. Via this domain, BAG proteins bind to the heat shock protein 70 (Hsp70), thereby acting as a co-chaperone regulating the activity of Hsp70. In addition to their antiapoptotic activity, all human BAG proteins have distinct functions in health and disease, and BAG3 in particular is the focus of many investigations. BAG3 has a modular protein domain composition offering the possibility for manifold interactions with other proteins. Various BAG3 functions are implicated in disorders including cancer, myopathies, and neurodegeneration. The discovery of its role in selective autophagy and the description of BAG3-mediated selective macroautophagy as an adaptive mechanism to maintain cellular homeostasis, under stress as well as during aging, make BAG3 a highly interesting target for future pharmacological interventions.

TrendsBAG3 appears to have multiple functions in health and disease.BAG3 is investigated in cancer, myopathy, and neurodegenerative disorders.The multimodal protein domain structure of BAG3 allows many interactions with intracellular signaling molecules.BAG3 has antiapoptotic functions as other members of the BAG protein family but the portfolio of activities has been extended to important functions in macroautophagy.BAG3-mediated selective macroautophagy is an adaptation of stressed and/or aging cells to maintain protein homeostasis.