HIP, A NOVEL COCHAPERONE INVOLVED IN THE EUKARYOTIC HSC70 HSP40 REACTION CYCLE/

The Hsc70-interacting protein Hip, a tetratricopeptide repeat protein, participates in the regulation of the eukaryotic 70 kDa heat shock co gnate Hsc70. One Hip oligomer binds the ATPase domains of at least two Hsc70 molecules dependent on activation of the Hsc70 ATPase by Hsp40. While hydrolysis remains the rate-limiting step in the ATPase cycle, Hip stabilizes the ADP state of Hsc70 that has a high affinity for sub strate protein. Through its own chaperone activity, Hip may contribute to the interaction of Hsc70 with various target proteins. We propose a mechanism for the regulation of eukaryotic Hsc70 that is distinct fr om that of bacterial Hsp70. The Hsc70/Hsp40/Hip system is apparently i ndependent of a GrpE-like nucleotide exchange factor.