Hsp90 and Cdc37 -- a chaperone cancer conspiracy.
The Hsp90 molecular chaperone system is involved in the activation of an important set of cell regulatory proteins, including many whose disregulation drives cancer. Recruitment of protein kinases to the Hsp90 system is mediated by the co-chaperone adaptor Cdc37 -- an essential protein whose overexpression is itself, oncogenic. Current structural, biochemical and biological studies of Cdc37 are beginning to unravel the nature of its interactions with Hsp90 and protein kinase clients, and implicate it as a key permissive factor in cell transformation by disregulated protein kinases. The central role of the Hsp90-Cdc37 chaperone complex makes it an important target for future anti-cancer drug development.
Pearl
Laurence H
LH
Section of Structural Biology, Institute of Cancer Research, Chester Beatty Laboratories, London, SW3 6JB, UK. laurence.pearl@icr.ac.uk
D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000502:physiology*; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D018833:Chaperonins; D019281:Dimerization; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*
C498362:CDC37 protein, human; D018797:Cell Cycle Proteins; D018841:HSP90 Heat-Shock Proteins; D018833:Chaperonins