The molecular chaperone Hsp90 regulates the folding of diverse signal transducers in all eukaryotes, profoundly affecting cellular circuitry. In fungi, Hsp90 influences development, drug resistance, and evolution. Hsp90 interacts with -10% of the proteome in the model yeast Saccharomyces cerevisiae, while only two interactions have been identified in Candida albicans, the leading fungal pathoge...

Heat shock protein 90 (Hsp90) is a significant target in the development of rational cancer therapy due to its role at the crossroads of multiple signaling pathways associated with cell proliferation and cell viability. The relevance of Hsp90 as a therapeutic target for numerous diseases states has prompted the identification and optimization of novel Hsp90 inhibitors as an emerging therapeutic...

Hsp90 is an essential and highly conserved modular molecular chaperone whose N and middle domains are separated by a disordered region termed the charged linker. Although its importance has been previously disregarded, because a minimal linker length is sufficient for Hsp90 activity, the evolutionary persistence of extensive charged linkers of divergent sequence in Hsp90 proteins of most eukary...

We have shown previously that the molecular chaperone heat shock protein 90 (Hsp90) is required for a proper centrosome function. Indeed, this Hsp90 function seems to be reflected in Polo-like kinase stability. Inhibition of Hsp90 in HeLa cells results in cell cycle arrest either in G2 stage or at the metaphase-anaphase transition. Here, we show that this inhibition leads to inactivation of the...

The aims of the present study were to estimate the affinity between 3,5-(E)-bis(3-methoxy-4-hydroxybenzal)-4-piperidinone hydrochloride (C0818) and heat shock protein 90 (Hsp90) and to investigate the inhibitory effects of this compound on Hsp90 ATPase activity. Fluorescence spectroscopy was used to examine the affinity between varying concentrations of C0818 and Hsp90, N-Hsp90, M-Hsp90 and C-H...

INrf2(Keap1) functions as an adapter for Cul3/Rbx1-mediated degradation of Nrf2. In response to stress, Nrf2 is released from INrf2 and translocates inside the nucleus leading to activation of cytoprotective proteins critical in protection against adverse effects including cancer. We demonstrate here a novel role of heat shock protein 90 (Hsp90) in control of the INrf2 and Nrf2 activation. Hsp9...

The molecular chaperone complex hsp90-p23 interacts with the dioxin receptor, a ligand-dependent basic helix-loop-helix (bHLH)/Per-Arnt-Sim domain transcription factor. Whereas biochemical and genetic evidence indicates that hsp90 is important for maintenance of a high-affinity ligand binding conformation of the dioxin receptor, the role of hsp90-associated proteins in regulation of the dioxin ...

The Hsp90 chaperone buffers development against a wide range of morphological changes in many organisms and in Drosophila masks the effects of hidden genetic variation. Theory predicts that genetic and nongenetic buffering will share common mechanisms. For example, it is argued that Hsp90 genetic buffering evolved solely as a by-product of environmental buffering, and that Hsp90 should mask mor...

Hsp90 is an essential chaperone responsible for trafficking a vast array of client proteins, which are substrates that Hsp90 regulates in eukaryotic cells under stress conditions. The ATP-binding N-terminal domain of Hsp90 (also known as a GHKL type ATPase domain) can serve as a specific drug target, because sufficient structural diversity in the ATP-binding pocket of Hsp90 allows for ortholog ...

The molecular chaperone Heat Shock Protein 90 (Hsp90) is essential for the function of various oncoproteins that are vital components of multiple signaling networks regulating cancer cell proliferation, survival, and metastasis. Hsp90 chaperone function is coupled to its ATPase activity, which can be inhibited by natural products such as the ansamycin geldanamycin (GA) and the resorcinol radici...