Heat shock protein 90 mediates macrophage activation by Taxol and bacterial lipopolysaccharide Journal Article


Authors: Byrd, C. A.; Bornmann, W.; Erdjument-Bromage, H.; Tempst, P.; Pavletich, N.; Rosen, N.; Nathan, C. F.; Ding, A.
Article Title: Heat shock protein 90 mediates macrophage activation by Taxol and bacterial lipopolysaccharide
Abstract: Taxol, a plant-derived antitumor agent, stabilizes microtubules. Taxol also elicits cell signals in a manner indistinguishable from bacterial lipopolysaccharide (LPS). LPS-like actions of Taxol are controlled by the lps gene and are independent of binding to the known Taxol target, β-tubulin. Using biotin-labeled Taxol, avidin-agarose affinity chromatography, and peptide mass fingerprinting, we identified two Taxol targets from mouse macrophages and brain as heat shock proteins (Hsps) of the 70- and 90-kDa families. Geldanamycin, a specific inhibitor of the Hsp 90 family, blocked the nuclear translocation of NF-κB and expression of tumor necrosis factor in macrophages treated with Taxol or with LPS. Geldanamycin did not block microtubule bundling by Taxol or macrophage activation by tumor necrosis factor. Thus, Taxol binds Hsps, and Hsp 90 helps mediate the activation of macrophages by Taxol and by LPS.
Keywords: immunohistochemistry; signal transduction; controlled study; dna-binding proteins; nonhuman; antineoplastic agents; drug targeting; paclitaxel; mass spectrometry; animal cell; mouse; animals; mice; beta tubulin; protein targeting; immunoglobulin enhancer binding protein; bacteria (microorganisms); animalia; nuclear proteins; tumor necrosis factor-alpha; recombinant tumor necrosis factor; brain; nf-kappa b; heat shock protein 90; hsp90 heat-shock proteins; quinones; heat shock protein 70; protein family; macrophages; microtubule; microtubules; benzoquinones; lactams, macrocyclic; biotinylation; geldanamycin; agarose; affinity chromatography; lipopolysaccharides; macrophage activation; bacterium lipopolysaccharide; avidin; priority journal; article
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Volume: 96
Issue: 10
ISSN: 0027-8424
Publisher: National Academy of Sciences  
Date Published: 1999-05-01
Start Page: 5645
End Page: 5650
Language: English
DOI: 10.1073/pnas.96.10.5645
PUBMED: 10318938
PROVIDER: scopus
PMCID: PMC21914
DOI/URL:
Notes: Article -- Export Date: 16 August 2016 -- Source: Scopus
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MSK Authors
  1. William Bornmann
    110 Bornmann
  2. Neal Rosen
    368 Rosen
  3. Paul J Tempst
    314 Tempst