[HTML][HTML] Akt forms an intracellular complex with heat shock protein 90 (Hsp90) and Cdc37 and is destabilized by inhibitors of Hsp90 function
Hsp90 is a chaperone required for the conformational maturation of certain signaling
proteins including Raf, cdk4, and steroid receptors. Natural products and synthetic small
molecules that bind to the ATP-binding pocket in the amino-terminal domain of Hsp90 inhibit
its function and cause the degradation of these client proteins. Inhibition of Hsp90 function in
cells causes down-regulation of an Akt kinase-dependent pathway required for D-cyclin
expression and retinoblastoma protein-dependent G 1 arrest. Intracellular Akt is associated …
proteins including Raf, cdk4, and steroid receptors. Natural products and synthetic small
molecules that bind to the ATP-binding pocket in the amino-terminal domain of Hsp90 inhibit
its function and cause the degradation of these client proteins. Inhibition of Hsp90 function in
cells causes down-regulation of an Akt kinase-dependent pathway required for D-cyclin
expression and retinoblastoma protein-dependent G 1 arrest. Intracellular Akt is associated …