title: Breaking BAG: The Co-Chaperone BAG3 in Health and Disease.
abstract: 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.
authors.affiliation: Institute of Pathobiochemistry, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany. Electronic address: cbehl@uni-mainz.de.
authors.forename: Christian
authors.initials: C
authors.lastname: Behl
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism / Q000502:physiology*; D001343:Autophagy / Q000502:physiology; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D009135:Muscular Diseases / Q000473:pathology; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D019636:Neurodegenerative Diseases / Q000378:metabolism / Q000473:pathology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C414431:BAG3 protein, human; D018840:HSP70 Heat-Shock Proteins
keywords: BAG1–BAG3 switch; Bcl-2; Hsc/Hsp70; macroautophagy; proteasome; protein quality control