Disease relevance of HSP90

• Our findings indicate for the first time that substantially decreased heart HSP90 is associated with HCM pigs with sudden death [1].
• Molecular cloning and characterization of porcine cDNA encoding a 90-kDa heat shock protein and its expression following hyperthermia [2].
• Exposure of PAEC to hypoxia also caused time-dependent decreases of heat shock protein 90 (HSP90) that were prevented by calpain inhibitor I and calpeptin [3].
• The molecular chaperone function of HSP90 is activated under heat-stress conditions [4].
• The amino acid sequences of three portions (total 47 amino acid residues) of lymphoma HSP90 were determined and they were homologous to those of the corresponding portions of Drosophila HSP83A and yeast HSP90 [5].

High impact information on HSP90

• When primary cultures of guinea pig gastric mucosal cells were exposed to heat (43 degree C), ethanol, hydrogen peroxide (H2O2), or diamide, heat shock proteins (HSP90, HSP70, HSP60, and HSC73) were rapidly synthesized [6].
• The presence of a nucleotide binding site on hsp90 was very controversial until x-ray structure of the hsp90 N-terminal domain, showing a nonconventional nucleotide binding site, appeared [7].
• Furthermore, we found that HSP90 prevents luciferase from irreversible thermal denaturation and enables it to refold when postincubated with reticulocyte lysates [8].
• Finally, we found that HSP90 activates CKII; an addition of HSP90 to CKII dramatically increased phosphorylation of exogenous substrates as well as the CKII beta subunit [9].
• We found that a preparation of the 90-kDa heat shock protein, HSP90, purified to apparent homogeneity, contains a serine/threonine kinase which phosphorylates HSP90 [9].

Biological context of HSP90

• We have isolated and sequenced cDNA clones encoding a 90-kDa heat shock protein (HSP90) from a porcine brain cDNA library [2].
• Moreover, the deduced amino acid sequence of the porcine hsp90 cDNA was 99.7% identical to that of the human counterpart, with a difference of only three amino acids in a total of 733 residues [2].
• HSP90 forms transient or stable complexes with several key proteins involved in signal transduction including protooncogenic protein kinases and nuclear receptors, it interacts with cellular structural elements such as actin-microfilament, tubulin-microtubule and intermediate filaments, and also exhibits conventional chaperone functions [10].
• The aim of the present study was to further characterize the plausible novel function of HSP90 on sperm motility [11].
• Hsp90 function is intimately linked to intrinsic ATP binding and hydrolysis activities, the latter of which is under the regulatory control of accessory factors [12].

Anatomical context of HSP90

• The changes in eNOS activity induced by modification of microtubules are due, at least in part, to the altered binding of HSP90 to eNOS protein [13].
• Exposure to Ang-1 caused an increase in endothelial cell migration, tube formation, and sprouting from PCAEC spheroids, and pharmacological blockage of HSP90 function or inhibition of PI3K-Akt pathway completely abolished these effects [14].
• HSP90 and Akt modulate Ang-1-induced angiogenesis via NO in coronary artery endothelium [14].
• HSP90 is one of the most abundant proteins in the cytosol of eukaryotic cells [10].
• Mouse liver HSP90 and porcine brain HSP90 were compared with mouse lymphoma HSP90 which was purified from T lymphoma cell line, L5178Y, by a modification of the previously reported method [5].

Associations of HSP90 with chemical compounds

• It has been reported that immunosuppressant cyclosporin A or FK506 binds to immunophilins in the cell and that these immunophilins make a complex with molecular chaperones HSP70 or HSP90 [15].
• Geldanamycin, a HSP90 inhibitor, prevented the taxol-induced increase in eNOS activity [13].
• Incubation of PAEC with nocodazole (50 microM) for 2-4 h induced a decrease in NO production, eNOS activity, and the amount of HSP90 binding to eNOS [13].
• CONCLUSIONS: Taken together, these data indicate that AMPK activity is essential for estradiol-induced eNOS activation via the promotion of eNOS interaction with HSP90 [16].
• However, inhibition of AMPK did not alter estradiol-induced eNOS phosphorylation at serine 1177 or threonine 495 but decreased eNOS interaction with HSP90 [16].

Other interactions of HSP90

• After 10 days of hypoxia, NO function is impaired in PAs despite preserved levels of NOS-3, HSP90, and caveolin-1 [17].
• NOS-3, HSP90, and caveolin-1 levels were similar in hypoxic and control PAs [17].
• Glucose-regulated protein of 94 kDa (GRP94), the endoplasmic reticulum Hsp90, is highly homologous to cytosolic Hsp90 [12].

Analytical, diagnostic and therapeutic context of HSP90

• METHODS: Heat shock proteins (HSPs) were detected by immunoblotting with antibody against HSP90, HSP70, heat shock cognate protein 70, or HSP60 [18].
• As determined by the molecular mass and isoelectric point on 2-dimensional gels and Western immunoblot with a specific 90 kDa heat shock protein (HSP90) monoclonal antibody, the unknown protein was identified as HSP90 [1].
• MALDI mass spectra of HSP90 samples after chemical cross-linking showed a high percentage of alpha-alpha homodimers [10].
• These results indicate that small-scale HPLC purification of HSP90 from porcine brain tissue can be readily accomplished, with high yield, using a convenient one-step purification method [19].
• In this paper, the interactions of ATP with native hsp90 and its recombinant N-terminal (positions 1-221) and C-terminal (positions 446-728) domains were studied by isothermal titration calorimetry, scanning differential calorimetry, and fluorescence spectroscopy [7].

References