The carboxyl terminus of the Hsc70-interacting protein (CHIP) is an Hsp70 co-chaperone as
well as an E3 ubiquitin ligase that protects cells from proteotoxic stress. The abilities of CHIP
to interact with Hsp70 and function as a ubiquitin ligase place CHIP at a pivotal position in
the protein quality control system, where its entrance into Hsp70-substrate complexes
partitions nonnative proteins toward degradation. However, the manner by which Hsp70
substrates are selected for ubiquitination by CHIP is not well understood. We discovered that …