Heat shock protein 70–Bcl2-associated athanogene 3 protein-protein interaction (Hsp70–BAG3 interaction)

The Hsp70–BAG3 protein-protein interaction is a pivotal scaffold for sensing proteotoxic stress in cells. Hsp70 is a molecular chaperone, and BAG3 is a multi-domain co-chaperone that connects Hsp70 to other stress response networks. This complex regulates protein folding, degradation, aggregation, and orchestrates signaling pathways controlling cell fate decisions, including apoptosis and survival. Dysregulation or mutation in BAG3 can result in abnormal aggregate formation, and both proteins are upregulated in various cancers and stress conditions. The complex is pharmacologically targetable, with small molecule inhibitors disrupting the interaction as a therapeutic strategy against cancer and certain myopathies. However, therapeutic targeting must consider the essential roles of chaperone function in normal physiology.

Other names

Hsp70–BAG3 complexHsp70–BAG3 PPI (Protein-Protein Interaction)Hsp70–Bag3 scaffoldHB complex

Disruption/blockade of the Hsp70–BAG3 interaction destabilizes the complex, alters chaperone-mediated protein quality control, and can induce apoptosis in cancer cells or prevent pathological protein aggregation in myopathies. Stabilizing the ADP-bound state of Hsp70 can block its binding to BAG3.