Functional specificity of co-chaperone interactions with Hsp90 client proteins.
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.
Riggs
Daniel L
DL
Department of Biochemistry and Molecular Biology, Mayo Clinic Scottsdale, Scottsdale, AZ 85259, USA.
Cox
Marc B
MB
Cheung-Flynn
Joyce
J
Prapapanich
Viravan
V
Carrigan
Patricia E
PE
Smith
David F
DF
D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism; D018833:Chaperonins; D029721:Drosophila Proteins / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D020104:Immunophilins / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D018832:Molecular Chaperones / Q000378:metabolism; D011506:Proteins / Q000737:chemistry / Q000378:metabolism; D013379:Substrate Specificity
C498362:CDC37 protein, human; D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D018841:HSP90 Heat-Shock Proteins; D047908:Intracellular Signaling Peptides and Proteins; D018832:Molecular Chaperones; D011506:Proteins; C103265:aryl hydrocarbon receptor-interacting protein; D018833:Chaperonins; D020104:Immunophilins