BAG family molecular chaperone regulator 3 (BAG3)

BAG family molecular chaperone regulator 3 (BAG3) is a co-chaperone protein encoded by the BAG3 gene that functions primarily in cellular protein quality control and stress responses[1][2]. BAG3 interacts with heat shock proteins such as HSP70 and HSPB8 to mediate chaperone-assisted selective autophagy, targeting aggregated or damaged proteins for degradation via the autophagic-lysosomal pathway[2]. It also bridges molecular chaperones and the cytoskeleton, ensuring cellular proteostasis, especially under mechanical or environmental stress[1]. BAG3 is expressed at high levels in muscle and is upregulated during cellular stress and in cancer[4]. Functionally, BAG3 supports cell survival by inhibiting apoptosis, promoting cell proliferation, and enabling cytoskeletal resilience. Disease relevance includes roles in cancer, neurodegeneration, cardiomyopathies, and muscle diseases[1][2][4]. Therapeutically, BAG3 has been explored as a target for modulating proteostasis in neurodegenerative disease, as well as sensitizing tumor cells to apoptosis. However, targeting BAG3 carries safety concerns due to its roles in vital homeostatic processes, especially in muscle and neural tissue[1][2][4].

Other names

BAG3BCL2 associated athanogene 3BAG cochaperone 3

Modulation of autophagy (especially selective macroautophagy for aggregated protein clearance)[2] Promotion of cell survival by inhibiting apoptosis (by interaction with BCL-2, HSP70, etc.)[2][4] Sensitization to apoptotic cell death when BAG3 is suppressed, notably with BH3-mimetics in cancer models[2]