Intense investigations of the Hsp90 chaperone were stimulated by the discovery that Hsp90 inhibitors serve as anticancer agents for many tumor cell lines.1'2 Further biological interest in Hsp90 comes from observations that Hsp90 levels mediate the relationship between genotype and phenotype and thus can impact evolutionary trajectories. 5 Hsp90 is an unusual chaperone because it matures a select set of substrates (referred to as clients) enriched for signal transduction proteins, including many kinases and steroid hormone receptors.6' These clients and their biological roles provide compelling motivation to understand the mechanism bv which Hsr>90 assists in client maturation.
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