Heat shock protein 90 (HSP90) is a molecular chaperone that supports the stability of client proteins. The proteasome is one of the targets for cancer therapy, and studies are underway to use proteasome inhibitors as anti-cancer drugs. In this study, we found that HSP90 was cleaved to a 55kDa protein after treatment with proteasome inhibitors including MG132 in leukemia cells but was not cleave...

The activator of Hsp90 ATPase 1, Aha1, has been shown to participate in the Hsp90 chaperone cycle by stimulating the low intrinsic ATPase activity of Hsp90. To elucidate the structural basis for ATPase stimulation of human Hsp90 by human Aha1, we have developed novel mass spectrometry approaches that demonstrate that the N- and C-terminal domains of Aha1 cooperatively bind across the dimer inte...

The 20 S proteasome has been suggested to play a critical role in mediating the degradation of abnormal proteins under conditions of oxidative stress and has been found in tight association with the molecular chaperone Hsp90. To elucidate the role of Hsp90 in promoting the degradation of oxidized calmodulin (CaMox), we have purified red blood cell 20 S proteasomes free of Hsp90 and assessed the...

Hsp90 is a molecular chaperone for many signal transducers and may influence evolution by releasing previously silent genetic variation in response to environmental change. In fungi separated by approximately 800 million years of evolution, Hsp90 potentiated the evolution of drug resistance in a different way, by enabling new mutations to have immediate phenotypic consequences. Resistance was a...

In this minireview we summarize evidence that the association of the glucocorticoid receptor (GR) with hsp90 may determine three functional states of the receptor. First, there is a direct correlation between hsp90 binding to the receptor and repression of DNA binding activity. Temperature-dependent dissociation of hsp90 from the cytosolic GR-hsp90 complex is promoted by hormone with simultaneo...

PURPOSE To examine the interaction of heat shock protein 90 (Hsp90) with the CB2 cannabinoid receptor in trabecular meshwork (TM) cells and to investigate the roles of Hsp90 in CB2 receptor-mediated cell signaling and actin cytoskeleton remodeling. METHODS Coimmunoprecipitation experiments and western blot analyses, using specific anti-CB2 and anti-Hsp90 antibodies, were performed to study th...

Hsp90 is a molecular chaperone, a vital protein that facilitates the folding and unfolding of a variety of proteins or ‘clients’. Kinases are one such client, with over half of the human kinome dependent on Hsp90 for activation (1). As its name suggests, Hsp90 is a heat shock protein and thus is highly expressed when the cell is under stress to ensure that proteins are folded and active. Its ex...

BACKGROUND Heat shock protein 90 (Hsp90) interacts with and stabilizes several oncogenic protein kinases (e.g., p185(erbB2), p60(v-src), and Raf-1) and is required for the stability and dominant-negative function of mutated p53 protein. Two unrelated antibiotics, geldanamycin and radicicol, bind specifically to an atypical nucleotide-binding pocket of Hsp90, a site that shares homology with the...

The 90-kDa heat shock protein (Hsp90) plays an important role in endothelial nitric-oxide synthase (eNOS) regulation. Besides acting as an allosteric enhancer, Hsp90 was shown to serve as a module recruiting Akt to phosphorylate the serine 1179/1177 (bovine/human) residue of eNOS. Akt is activated by the phosphorylation of 3-phosphoinositide-dependent kinase 1 (PDK1). Whether PDK1 is involved i...

The molecular chaperone Hsp90 orchestrates regulatory circuitry governing fungal morphogenesis, biofilm development, drug resistance, and virulence. Hsp90 functions in concert with co-chaperones to regulate stability and activation of client proteins, many of which are signal transducers. Here, we characterize the first Hsp90 co-chaperone in the leading human fungal pathogen, Candida albicans. ...