How do J-proteins get Hsp70 to do so many different things?

Abstract

Hsp70 chaperone machineries play pivotal roles in a wide array of fundamental biological processes, through their facilitation of protein folding, disaggregation and remodeling. Hsp70’s obligate J-protein co-chaperones drive much of this remarkable multi-functionality, with most Hsp70s having multiple J-protein partners. Recent data suggest that J-protein-driven versatility is substantially due to precise localization within the cell and specificity of substrate protein binding. However, this relatively simple view belies the intricacy of J-protein function. Examples are emerging of J-protein interactions with Hsp70 and other chaperones, as well as integration into broader cellular networks. These interactions fine-tune, in critical ways, the ability of Hsp70 to participate in diverse cellular processes.