Biological activities of HAP46/BAG-1. The HAP46/BAG-1 protein: regulator of HSP70 chaperones, DNA-binding protein and stimulator of transcription.

HAP46/BAG-1M and its isoforms affect the protein-folding activities of mammalian HSP70 chaperones. They interact with the ATP-binding domain of HSP70 or HSC70, leaving the substrate-binding site available for further interactions. Trimeric complexes can therefore form with, for example, transcription factors. Moreover, HAP46/BAG-1M and the larger isoform HAP50/BAG-1L bind to DNA non-specifically and enhance transcription in vitro and upon overexpression in intact cells. These factors are linked to positive effects on cell proliferation and survival. This review focuses on DNA-binding activity and transcriptional stimulation by HAP46/BAG-1M, and presents a molecular model for the underlying mechanism. It is proposed that transcription factors are recruited into complexes with HAP46/BAG-1M or HAP50/BAG-1L through HSP70/HSC70 and that response-element-bound complexes that contain HAP46/BAG-1M and/or HAP50/BAG-1L along with HSP70s target and affect the basal transcription machinery.