Hsp90 reaches new heights

Introduction Hsp90 (heat-shock protein 90) is an abundant molecular chaperone, but its function seems to be restricted to the folding of proteins involved in cell signalling, such as transcription factors and protein kinases. This restricted set of ‘clients’ (see Fig. 1) makes Hsp90 an attractive target for cancer therapeutics. As an anti-Hsp90 drug is now in clinical trials, the meeting was relevant to a broad range of scientists interested in its chaperone activity. However, even with this clinical relevance, a meeting devoted to just one chaperone might seem like too much of a good thing, unless one takes into account the myriad of co-chaperones that regulate Hsp90. These co-chaperones modulate the ATPase activity of Hsp90 and many of them have intrinsic chaperone activity of their own, providing some measure of specificity for different Hsp90 clients. There is also some crossover between different chaperone machineries, as some co-chaperones interact with Hsp70 as well as Hsp90. The conference was opened by D. Smith (Scottsdale, AZ, USA), who gave a historical perspective on the interactions of Hsp90 and its co-chaperones with steroid receptors (reviewed by Pratt & Toft, 1997). His presentation began with a review of the work of Toft and Gorksi from the late 1960s, in which an oestrogen receptor was identified and found to exist in a large complex of proteins. Smith followed the identification and characterization of Hsp90 and other receptor-associated chaperones in this complex through to his recent studies on the regulation of the hormone-binding affinity of Hsp90-bound immunophilins. The theme of Hsp90 regulation, in particular by Hsp90-binding co-chaperones, and the variety of protein clients and physiological processes that are affected by the Hsp90 machinery was continued throughout the meeting.