Fig. 2

BAG2 interacts with the molecular chaperone Hsp70, which plays a prominent role in protein homeostasis. BAG2 accelerates ADP dissociation from Hsp70 and promotes Hsp70-mediated protein refolding. BAG2 is also an inhibitor of the Hsp70-binding E3 ubiquitin ligase CHIP and inhibits CHIP-mediated ubiquitination. Importantly, BAG2 inhibits tau ubiquitination, delivering phosphorylated tau to the proteasome for degradation via a ubiquitin-independent pathway. (+) indicates promoting, (−) indicates inhibiting, Ub indicates ubiquitin and UPS indicates the ubiquitin–proteasome system