Functional Specificity of Co-Chaperone Interactions with Hsp90 Client Proteins

Abstract

A wide array of proteins in signal transduction pathways depend on Hsp90 and other chaperone components for functional maturation, regulation, and stability. Among these Hsp90 client proteins are steroid receptors, members from other classes of transcription factors, and representatives of both serine/threonine and tyrosine kinase families. Typically, dynamic complexes form on the client protein, and these consist of Hsp90- plus bound co-chaperones that often have enzymatic activities. In addition to its direct influence on client folding, Hsp90 locally concentrates co-chaperone activity within the client complex, and dynamic exchange of co-chaperones on Hsp90 facilitates sampling of co-chaperone activities that may, or may not, act on the client protein. We are just beginning to understand the nature of biochemical and molecular interactions between co-chaperone and Hsp90-bound client. This review focuses on the differential effects of Hsp90 co-chaperones toward client protein function and on the specificity that allows co-chaperones to discriminate between even closely related clients.

Keywords:

• Hsp90
• immunophilin
• co-chaperone
• Cdc37
• Xap2
• FKBP52
• FKBP51
• CyP40
• PP5

Editor: Elizabeth A. Craig

The authors would like to thank Drs. Robert Matts, Gary Perdew, Avrom Caplan and anonymous reviewers for their critical reading of the manuscript and insightful suggestions. Studies in the Smith laboratory are supported by NIH R01DK48218, NIH R01DK44923, and the Mayo Foundation.