Hsp90: Chaperoning signal transduction

Hsp90 is an ATP dependent molecular chaperone involved in the folding and a ctivation of an unknown number of substrate proteins. These substrate prote ins include protein kinases and transcription factors. Consistent with this task, Hsp90 is an essential protein in all eucaryotes. The interaction of Hsp90 with its substrate proteins involves the transient formation of multi protein complexes with a set of highly conserved partner proteins. The spec ific function of each component in the processing of substrates is still un known. Large ATP-dependent conformational changes of Hsp90 occur during the hydrolysis reaction and these changes are thought to drive the chaperone c ycle. Natural inhibitors of the ATPase activity, like geldanamycin and radi cicol, block the processing of Hsp90 substrate proteins. As many of these s ubstrates are critical elements in signal transduction, Hsp90 seems to intr oduce an additional level of regulation.