Regulation of Signaling Protein Function and Trafficking by the hsp90/hsp70-Based Chaperone Machinery

Nearly 100 proteins are known to be regulated by hsp90. Most of these substrates or "client proteins" are involved in signal transduction, and they are brought into complex with hsp90 by a multiprotein hsp90/hsp70-based chaperone machinery. In addition to binding substrate proteins at the chaperone site(s), hsp90 binds cofactors at other sites that are part of the heterocomplex assembly machinery as well as immunophilins that connect assembled substrate*hsp90 complexes to protein-trafficking systems. In the 5 years since we last reviewed this subject, much has been learned about hsp90 structure, nucleotide-binding, and cochaperone interactions; the most important concept is that ATP hydrolysis by an intrinsic…