The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

Hsp90ab1  -  heat shock protein 90 alpha (cytosolic),...

Mus musculus

Synonyms: 90kDa, AL022974, C81438, HSP 84, HSP84, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of Hsp90ab1


High impact information on Hsp90ab1

  • We examined the therapeutic effects of 17-allylamino-17-demethoxygeldanamycin (17-AAG), a potent Hsp90 inhibitor, and its ability to degrade polyglutamine-expanded mutant AR [1].
  • 17-AAG, an Hsp90 inhibitor, ameliorates polyglutamine-mediated motor neuron degeneration [1].
  • Hsp90 chaperones protein folding in vitro [5].
  • The heat-shock protein Hsp90 is the most abundant constitutively expressed stress protein in the cytosol of eukaryotic cells, where it participates in the maturation of other proteins, modulation of protein activity in the case of hormone-free steroid receptors, and intracellular transport of some newly synthesized kinases [5].
  • Modulating molecular chaperone Hsp90 functions through reversible acetylation [6].

Chemical compound and disease context of Hsp90ab1


Biological context of Hsp90ab1

  • The common tetratricopeptide repeat acceptor site for steroid receptor-associated immunophilins and hop is located in the dimerization domain of Hsp90 [12].
  • Chromosomal analysis indicated that hsp84-related sequences are on at least three different chromosomes [13].
  • The steady-state levels of HSP86 and HSP84 paralleled the pattern of the expression of their respective mRNAs, suggesting that regulation at the level of translation was not a major mechanism controlling hsp90 gene expression in testicular cells [14].
  • The amino acid sequences deduced from the contiguous ORF of the hsp84 and the hsp84-related cDNA coincide with the N-terminal sequence of formerly identified 84-kDa and 86-kDa tumour-specific transplantation antigens (Ullrich et al., 1986) [15].
  • Hsp90 was required for signal transducers and activators of transcription 1 phosphorylation, and in its absence, Janus kinase (JAK) 1/2 were degraded by the proteosome [16].

Anatomical context of Hsp90ab1

  • By contrast, the HSP84 protein was detected in the somatic cells of the testis rather than in germ cells [14].
  • The biological consequences were suggested by experiments showing that T cell activation by interferon-gamma-primed macrophages and the antiviral response of interferons required Hsp90 [16].
  • The interaction between Hsp90 and eNOS enhances the activation of the enzyme in cells and in intact blood vessels leading to NO production [17].
  • Geldanamycin (0.1, 0.3, 1 mg kg(-1)), a specific inhibitor of Hsp-90, that inhibits endothelium-dependent relaxations of the rat aorta, mesentery and middle artery inhibits carrageenan-induced mouse paw oedema in a dose dependent manner [17].
  • In various cellular models, increased levels of Hsp70 and Hsp90 promote tau solubility and tau binding to microtubules, reduce insoluble tau and cause reduced tau phosphorylation [18].

Associations of Hsp90ab1 with chemical compounds

  • Comparison of the NH2-terminal and CNBr-fragment sequence data to the sequences of the yeast and Drosophila heat shock proteins (Hsp90 and Hsp83, respectively) reveals that 73 of 91 residues compared are identical [19].
  • We now report that this regulation occurred with both the HSP86 and HSP84 forms of HSP90 as well as with the 94-kilodalton glucose-regulated protein [20].
  • Geldanamycin treatment, which specifically inhibits Hsp90, caused a partial loss of wild-type Galpha(12) and a complete loss of the Cys-11 mutant from the lipid rafts and the appearance of a higher molecular weight form of Galpha(12) in the soluble fractions [21].
  • Surprisingly, we found, using highly purified proteins, that only Hsp90 and Hsc70 are required for the activation of glucocorticoid receptors in the presence of steroids; in the absence of steroids, either p23 or molybdate are also required as reported previously [22].
  • Aldosterone led to increased association of Src with HSP84 [23].

Physical interactions of Hsp90ab1

  • Hsp90 is reported to bind to and stabilize Akt kinase and also to bind to DSG [24].
  • Despite belonging to a class of NR not known to interact with cytosolic chaperone complexes, we have recently shown that PPARalpha interacts with heat shock protein 90 (Hsp90), although the biological consequence of this association was unknown [25].

Regulatory relationships of Hsp90ab1


Other interactions of Hsp90ab1


Analytical, diagnostic and therapeutic context of Hsp90ab1

  • Immunoprecipitation analysis revealed that a 70-kDa protein coprecipitated with the HSP86/HSP84 proteins in testicular homogenates [14].
  • Northern blot hybridization experiments reveal a 2.6-kb poly(A)+RNA when probed with the hsp84 clone and a 2.85-kb signal with the hsp84-related cDNA [15].
  • We verified array results with RT-PCR and Northern blotting for three genes which are related to oxidative damage closely, including Hsp84, Hsp86 and YB-1 [31].
  • These results suggest that Hsp90 inhibitors can effectively suppress Akt activity in animal models of human cancer at nontoxic doses, thus sensitizing tumor cells to proapoptotic stimuli [32].
  • Vaccination of mice with GRP94/gp96, the endoplasmic reticulum Hsp90, elicits a variety of immune responses sufficient for tumor rejection and the suppression of metastatic tumor progression [33].


  1. 17-AAG, an Hsp90 inhibitor, ameliorates polyglutamine-mediated motor neuron degeneration. Waza, M., Adachi, H., Katsuno, M., Minamiyama, M., Sang, C., Tanaka, F., Inukai, A., Doyu, M., Sobue, G. Nat. Med. (2005) [Pubmed]
  2. Geldanamycin induces heat shock protein 70 and protects against MPTP-induced dopaminergic neurotoxicity in mice. Shen, H.Y., He, J.C., Wang, Y., Huang, Q.Y., Chen, J.F. J. Biol. Chem. (2005) [Pubmed]
  3. Role of the heat shock protein 90 in immune response stimulation by bacterial DNA and synthetic oligonucleotides. Zhu, F.G., Pisetsky, D.S. Infect. Immun. (2001) [Pubmed]
  4. Comparison of 17-dimethylaminoethylamino-17-demethoxy-geldanamycin (17DMAG) and 17-allylamino-17-demethoxygeldanamycin (17AAG) in vitro: effects on Hsp90 and client proteins in melanoma models. Smith, V., Sausville, E.A., Camalier, R.F., Fiebig, H.H., Burger, A.M. Cancer Chemother. Pharmacol. (2005) [Pubmed]
  5. Hsp90 chaperones protein folding in vitro. Wiech, H., Buchner, J., Zimmermann, R., Jakob, U. Nature (1992) [Pubmed]
  6. Modulating molecular chaperone Hsp90 functions through reversible acetylation. Aoyagi, S., Archer, T.K. Trends Cell Biol. (2005) [Pubmed]
  7. 17-Allylamino-17-demethoxygeldanamycin induces the degradation of androgen receptor and HER-2/neu and inhibits the growth of prostate cancer xenografts. Solit, D.B., Zheng, F.F., Drobnjak, M., Münster, P.N., Higgins, B., Verbel, D., Heller, G., Tong, W., Cordon-Cardo, C., Agus, D.B., Scher, H.I., Rosen, N. Clin. Cancer Res. (2002) [Pubmed]
  8. Hormone-refractory breast cancer remains sensitive to the antitumor activity of heat shock protein 90 inhibitors. Beliakoff, J., Bagatell, R., Paine-Murrieta, G., Taylor, C.W., Lykkesfeldt, A.E., Whitesell, L. Clin. Cancer Res. (2003) [Pubmed]
  9. Biologic and biochemical properties of detergent-solubilized tumor-specific transplantation antigen from a simian virus 40-induced neoplasm: brief communication. Natori, T., Law, L.W., Appella, E. J. Natl. Cancer Inst. (1977) [Pubmed]
  10. Noncytolytic extraction of murine tumor-specific transplantation antigens with the nonionic detergent octyl-beta-D-glucopyranoside. LeGrue, S.J., Macek, C.M., Kahan, B.D. J. Natl. Cancer Inst. (1982) [Pubmed]
  11. Effect of continuous administration of interleukin 2 on active specific chemoimmunotherapy with extracted tumor-specific transplantation antigen and cyclophosphamide. Naito, K., Pellis, N.R., Kahan, B.D. Cancer Res. (1988) [Pubmed]
  12. The common tetratricopeptide repeat acceptor site for steroid receptor-associated immunophilins and hop is located in the dimerization domain of Hsp90. Carrello, A., Ingley, E., Minchin, R.F., Tsai, S., Ratajczak, T. J. Biol. Chem. (1999) [Pubmed]
  13. Cloning and nucleotide sequence of the murine hsp84 cDNA and chromosome assignment of related sequences. Moore, S.K., Kozak, C., Robinson, E.A., Ullrich, S.J., Appella, E. Gene (1987) [Pubmed]
  14. HSP86 and HSP84 exhibit cellular specificity of expression and co-precipitate with an HSP70 family member in the murine testis. Gruppi, C.M., Wolgemuth, D.J. Dev. Genet. (1993) [Pubmed]
  15. Heat-shock proteins, Hsp84 and Hsp86, of mice and men: two related genes encode formerly identified tumour-specific transplantation antigens. Hoffmann, T., Hovemann, B. Gene (1988) [Pubmed]
  16. The heat shock protein 90-CDC37 chaperone complex is required for signaling by types I and II interferons. Shang, L., Tomasi, T.B. J. Biol. Chem. (2006) [Pubmed]
  17. Geldanamycin, an inhibitor of heat shock protein 90 (Hsp90) mediated signal transduction has anti-inflammatory effects and interacts with glucocorticoid receptor in vivo. Bucci, M., Roviezzo, F., Cicala, C., Sessa, W.C., Cirino, G. Br. J. Pharmacol. (2000) [Pubmed]
  18. Chaperones increase association of tau protein with microtubules. Dou, F., Netzer, W.J., Tanemura, K., Li, F., Hartl, F.U., Takashima, A., Gouras, G.K., Greengard, P., Xu, H. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  19. A mouse tumor-specific transplantation antigen is a heat shock-related protein. Ullrich, S.J., Robinson, E.A., Law, L.W., Willingham, M., Appella, E. Proc. Natl. Acad. Sci. U.S.A. (1986) [Pubmed]
  20. Estrogenic regulation of murine uterine 90-kilodalton heat shock protein gene expression. Shyamala, G., Gauthier, Y., Moore, S.K., Catelli, M.G., Ullrich, S.J. Mol. Cell. Biol. (1989) [Pubmed]
  21. Hsp90 interactions and acylation target the G protein Galpha 12 but not Galpha 13 to lipid rafts. Waheed, A.A., Jones, T.L. J. Biol. Chem. (2002) [Pubmed]
  22. The molecular chaperones Hsp90 and Hsc70 are both necessary and sufficient to activate hormone binding by glucocorticoid receptor. Rajapandi, T., Greene, L.E., Eisenberg, E. J. Biol. Chem. (2000) [Pubmed]
  23. Aldosterone rapidly activates Src kinase in M-1 cells involving the mineralocorticoid receptor and HSP84. Braun, S., Lösel, R., Wehling, M., Boldyreff, B. FEBS Lett. (2004) [Pubmed]
  24. 15-Deoxyspergualin inhibits Akt kinase activation and phosphatidylcholine synthesis. Kawada, M., Masuda, T., Ishizuka, M., Takeuchi, T. J. Biol. Chem. (2002) [Pubmed]
  25. Heat shock protein-90 (Hsp90) acts as a repressor of peroxisome proliferator-activated receptor-alpha (PPARalpha) and PPARbeta activity. Sumanasekera, W.K., Tien, E.S., Davis, J.W., Turpey, R., Perdew, G.H., Vanden Heuvel, J.P. Biochemistry (2003) [Pubmed]
  26. Geldanamycin inhibits the production of inflammatory cytokines in activated macrophages by reducing the stability and translation of cytokine transcripts. Wax, S., Piecyk, M., Maritim, B., Anderson, P. Arthritis Rheum. (2003) [Pubmed]
  27. Murine 86- and 84-kDa heat shock proteins, cDNA sequences, chromosome assignments, and evolutionary origins. Moore, S.K., Kozak, C., Robinson, E.A., Ullrich, S.J., Appella, E. J. Biol. Chem. (1989) [Pubmed]
  28. Stress-inducible, murine protein mSTI1. Characterization of binding domains for heat shock proteins and in vitro phosphorylation by different kinases. Lässle, M., Blatch, G.L., Kundra, V., Takatori, T., Zetter, B.R. J. Biol. Chem. (1997) [Pubmed]
  29. Messenger RNA expression of heat shock proteins (HSPs) during ocular development. Tanaka, Y., Kobayashi, K., Kita, M., Kinoshita, S., Imanishi, J. Curr. Eye Res. (1995) [Pubmed]
  30. Conformational activation of a basic helix-loop-helix protein (MyoD1) by the C-terminal region of murine HSP90 (HSP84). Shaknovich, R., Shue, G., Kohtz, D.S. Mol. Cell. Biol. (1992) [Pubmed]
  31. Acupuncture regulates the aging-related changes in gene profile expression of the hippocampus in senescence-accelerated mouse (SAMP10). Ding, X., Yu, J., Yu, T., Fu, Y., Han, J. Neurosci. Lett. (2006) [Pubmed]
  32. Inhibition of heat shock protein 90 function down-regulates Akt kinase and sensitizes tumors to Taxol. Solit, D.B., Basso, A.D., Olshen, A.B., Scher, H.I., Rosen, N. Cancer Res. (2003) [Pubmed]
  33. GRP94/gp96 elicits ERK activation in murine macrophages. A role for endotoxin contamination in NF-kappa B activation and nitric oxide production. Reed, R.C., Berwin, B., Baker, J.P., Nicchitta, C.V. J. Biol. Chem. (2003) [Pubmed]
WikiGenes - Universities