Heat shock protein 90 (hsp90) is a chaperone required for the proper folding and trafficking of many proteins involved in signal transduction. We tested whether hsp90 plays a role as a chaperone for GC-A, the membrane guanylate cyclase that acts as a receptor for atrial natriuretic peptide (ANP). When cultured cells expressing recombinant GC-A were treated with geldanamycin, an inhibitor of hsp...

There is a conserved ATPase domain in topoisomerase II (topo II) and heat shock protein 90 (Hsp90) which belong to the GHKL (gyrase, Hsp90, histidine kinase, and MutL) family. The inhibitors that target each of topo II and Hsp90 are intensively studied as anti-cancer drugs since they play very important roles in cell proliferation and survival. Therefore the development of dual targeting anti-c...

The 90 kDa heat shock protein (Hsp90) induces the condensation of the chromatin structure [Csermely, P., Kajtár, J., Hollósi, M., Oikarinen, J., and Somogyi, J. (1994) Biochem. Biophys. Res. Commun. 202, 1657-1663]. In our present studies we used surface plasmon resonance measurements to demonstrate that Hsp90 binds histones H1, H2A, H2B, H3 and H4 with high affinity having dissociation constan...

The cochaperone Sti1/Hop physically links Hsp70 and Hsp90. The protein exhibits one binding site for Hsp90 (TPR2A) and two binding sites for Hsp70 (TPR1 and TPR2B). How these sites are used remained enigmatic. Here we show that Sti1 is a dynamic, elongated protein that consists of a flexible N-terminal module, a long linker and a rigid C-terminal module. Binding of Hsp90 and Hsp70 regulates the...

We previously reported an association between elevated serum antibody titers to the 90-kDa human heat shock protein (Hsp90), periodontal health and colonization by Porphyromonas gingivalis. In this study, we examined the cellular localization of the Hsp90 homologue of P. gingivalis. Cultures of P. gingivalis were heat-stressed (45 degrees C) and examined for localization of the Hsp90 homologue....

Hsp90 is an abundant molecular chaperone essential to the establishment of many cellular regulation and signal transduction systems, but remains one of the least well described chaperones. The biochemical mechanism of protein folding by Hsp90 is poorly understood, and the direct involvement of ATP has been particularly contentious. Here we demonstrate in vitro an inherent ATPase activity in bot...

Prostate cancer is hormone-dependent and the androgen receptor (AR) involved in its development. AR a transcription factor that activated by ligand binding, result translocation into nucleus, where it initiates gene transcription. In an inactive state cytoplasm exists as complex with heat shock protein 90 (HSP90) some other proteins. When agonist binds, conformational change occurs, resulting H...

Molecular chaperones are cellular machines that facilitate protein folding. The crystal structures of HtpG, the Escherichia coli homolog of hsp90, reported in this issue (Shiau et al., 2006) together with the recently published structures of an hsp90-cochaperone complex (Ali et al., 2006) and an hsp90-client protein complex (Vaughan et al., 2006), reveal exciting insights into the hsp90 reactio...

The molecular chaperone Hsp90 is a hub of protein homeostasis and regulatory circuitry. Hsp90 function is regulated by posttranslational modifications including acetylation in mammals; however, whether this regulation is conserved remains unknown. In fungi, Hsp90 governs the evolution of drug resistance by stabilizing signal transducers. Here, we establish that pharmacological inhibition of lys...

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...