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Gene Review

HSP90AA2P  -  heat shock protein 90kDa alpha (cytosolic)...

Homo sapiens

Synonyms: HSP90AA2, HSP90ALPHA, HSPCA, HSPCAL3, Heat shock 90 kDa protein 1 alpha-like 3
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Disease relevance of HSP90AA2


High impact information on HSP90AA2

  • Hsp90alpha chaperones large C-terminally extended proteolytic intermediates in the MHC class I antigen processing pathway [6].
  • Inhibition of extracellular hsp90 alpha decreases both MMP2 activity and invasiveness [7].
  • Upon exposure of cells to heat shock, the heavy metal cadmium, or the amino acid analogue azetidine, transcription at the hsp90alpha and hsp70 gene loci is strongly induced, and both hsp transcription sites become associated with speckles in >90% of the cells [8].
  • BDGA, used to characterize the kinetics of ligand-Hsp90 interactions, was found to bind Hsp90alpha with k(off) = 2.5 x 10(-3) min(-1), t(1/2) = 4.6 h, and Ki* = 10 nM [9].
  • We demonstrate that transcription of the gene encoding a 70-kDa heat shock protein (hsp70) is diminished upon heat shock in Y79 human retinoblastoma cells (which are of neuronal origin) despite both the activation of heat shock factor 1 and induced transcription of another heat shock gene, hsp90 alpha [10].

Chemical compound and disease context of HSP90AA2


Biological context of HSP90AA2


Anatomical context of HSP90AA2


Associations of HSP90AA2 with chemical compounds

  • Both of these molecular chaperones displayed ATPase activity and the ability to refold heat-inactivated luciferase in a geldanamycin- and radicicol-sensitive manner, suggesting that post-translational modifications are not involved in the modulation of Hsp90alpha activity [18].
  • The human double-stranded DNA-activated protein kinase phosphorylates the 90-kDa heat-shock protein, hsp90 alpha at two NH2-terminal threonine residues [15].
  • We describe the 1.75 A resolution crystal structure of human Hsp90 alpha (residues 9-236) complexed with 17-desmethoxy-17-N,N-dimethylaminoethylamino-geldanamycin (17-DMAG) [19].
  • We report here the structures of the water soluble 8-aryl-sulfanyl adenine class Hsp90 inhibitors, 1 (PU-H71) and 2 (PU-H64), in complex with the N-terminal domain of human Hsp90alpha [20].
  • Growth factors acting via tyrosine kinase receptors induce HSP90 alpha gene expression [21].

Physical interactions of HSP90AA2

  • In this study, we reported that small glutamine-rich TPR-containing protein (SGT) interacted with not only Hsp90alpha but also Hsp90beta [22].
  • We identified phosphorylations of the HSP90 subunits within the AhR complex at Ser225 and Ser254 of HSP90beta and Ser230 of HSP90alpha [23].
  • However, the C-terminal 326 amino acids of GRP94 failed to form a complex with HSP90 alpha [24].
  • Inhibition of LRP1 binding to extracellular HSP90alpha by neutralizing antibodies or genetic silencing of the LRP1 receptor by RNAi completely nullified hypoxia-driven HK migration [25].

Regulatory relationships of HSP90AA2


Other interactions of HSP90AA2

  • The HSP90 family of heat-shock proteins (encoded by genes for HSP90 alpha and beta) constitutes one of the major groups of proteins that are synthesized at increased rates in response to heat and other forms of stress [1].
  • The human recombinant Hsp90 alpha-isoform as well as bovine brain Hsp90 were purified to homogeneity [18].
  • Co-immunoprecipitation with anti-Hsp90alpha antibody followed by immunoblotting with DO-1 confirmed that p53 and Hsp90alpha were interacting proteins [28].
  • PRIMA-1 treatment also resulted in the translocation of Hsp90alpha to the nucleus by 8 hours [28].
  • The suppression of the hsp70.1 promoter is not caused by impaired function of HSF1, since HSF1 is equally activated in all cell types and occupies another heat-inducible promoter, hsp90 alpha [29].

Analytical, diagnostic and therapeutic context of HSP90AA2


  1. Mapping of the gene family for human heat-shock protein 90 alpha to chromosomes 1, 4, 11, and 14. Ozawa, K., Murakami, Y., Eki, T., Soeda, E., Yokoyama, K. Genomics (1992) [Pubmed]
  2. Effects of HIV protease inhibitor ritonavir on Akt-regulated cell proliferation in breast cancer. Srirangam, A., Mitra, R., Wang, M., Gorski, J.C., Badve, S., Baldridge, L., Hamilton, J., Kishimoto, H., Hawes, J., Li, L., Orschell, C.M., Srour, E.F., Blum, J.S., Donner, D., Sledge, G.W., Nakshatri, H., Potter, D.A. Clin. Cancer Res. (2006) [Pubmed]
  3. Study of heat shock protein HSP90 alpha, HSP70, HSP27 mRNA expression in human acute leukemia cells. Xiao, K., Liu, W., Qu, S., Sun, H., Tang, J. J. Tongji Med. Univ. (1996) [Pubmed]
  4. Intracellular localization of the 90 kDA heat shock protein (HSP90alpha) determined by expression of a EGFP-HSP90alpha-fusion protein in unstressed and heat stressed 3T3 cells. Langer, T., Rosmus, S., Fasold, H. Cell Biol. Int. (2003) [Pubmed]
  5. Extracellular roles for the molecular chaperone, hsp90. Eustace, B.K., Jay, D.G. Cell Cycle (2004) [Pubmed]
  6. Hsp90alpha chaperones large C-terminally extended proteolytic intermediates in the MHC class I antigen processing pathway. Kunisawa, J., Shastri, N. Immunity (2006) [Pubmed]
  7. Functional proteomic screens reveal an essential extracellular role for hsp90 alpha in cancer cell invasiveness. Eustace, B.K., Sakurai, T., Stewart, J.K., Yimlamai, D., Unger, C., Zehetmeier, C., Lain, B., Torella, C., Henning, S.W., Beste, G., Scroggins, B.T., Neckers, L., Ilag, L.L., Jay, D.G. Nat. Cell Biol. (2004) [Pubmed]
  8. Intron-independent association of splicing factors with active genes. Jolly, C., Vourc'h, C., Robert-Nicoud, M., Morimoto, R.I. J. Cell Biol. (1999) [Pubmed]
  9. A biochemical rationale for the anticancer effects of Hsp90 inhibitors: slow, tight binding inhibition by geldanamycin and its analogues. Gooljarsingh, L.T., Fernandes, C., Yan, K., Zhang, H., Grooms, M., Johanson, K., Sinnamon, R.H., Kirkpatrick, R.B., Kerrigan, J., Lewis, T., Arnone, M., King, A.J., Lai, Z., Copeland, R.A., Tummino, P.J. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  10. Deficient induction of human hsp70 heat shock gene transcription in Y79 retinoblastoma cells despite activation of heat shock factor 1. Mathur, S.K., Sistonen, L., Brown, I.R., Murphy, S.P., Sarge, K.D., Morimoto, R.I. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  11. Involvement of human heat shock protein 90 alpha in nicotine-induced apoptosis. Wu, Y.P., Kita, K., Suzuki, N. Int. J. Cancer (2002) [Pubmed]
  12. Heat shock protein 90alpha-dependent translocation of annexin II to the surface of endothelial cells modulates plasmin activity in the diabetic rat aorta. Lei, H., Romeo, G., Kazlauskas, A. Circ. Res. (2004) [Pubmed]
  13. Molecular variation of human HSP90alpha and HSP90beta genes in Caucasians. Passarino, G., Cavalleri, G.L., Stecconi, R., Franceschi, C., Altomare, K., Dato, S., Greco, V., Luca Cavalli Sforza, L., Underhill, P.A., de Benedictis, G. Hum. Mutat. (2003) [Pubmed]
  14. STAT3 and MAPK signaling maintain overexpression of heat shock proteins 90{alpha} and {beta} in multiple myeloma cells, which critically contribute to tumor-cell survival. Chatterjee, M., Jain, S., St??hmer, T., Andrulis, M., Ungeth??m, U., Kuban, R.J., Lorentz, H., Bommert, K., Topp, M., Kr??mer, D., M??ller-Hermelink, H.K., Einsele, H., Greiner, A., Bargou, R.C. Blood (2007) [Pubmed]
  15. The human double-stranded DNA-activated protein kinase phosphorylates the 90-kDa heat-shock protein, hsp90 alpha at two NH2-terminal threonine residues. Lees-Miller, S.P., Anderson, C.W. J. Biol. Chem. (1989) [Pubmed]
  16. The carboxy-terminal region of mammalian HSP90 is required for its dimerization and function in vivo. Minami, Y., Kimura, Y., Kawasaki, H., Suzuki, K., Yahara, I. Mol. Cell. Biol. (1994) [Pubmed]
  17. Protein surveillance machinery in brains with spinocerebellar ataxia type 3: redistribution and differential recruitment of 26S proteasome subunits and chaperones to neuronal intranuclear inclusions. Schmidt, T., Lindenberg, K.S., Krebs, A., Schöls, L., Laccone, F., Herms, J., Rechsteiner, M., Riess, O., Landwehrmeyer, G.B. Ann. Neurol. (2002) [Pubmed]
  18. Hsp90 chaperones wild-type p53 tumor suppressor protein. Walerych, D., Kudla, G., Gutkowska, M., Wawrzynow, B., Muller, L., King, F.W., Helwak, A., Boros, J., Zylicz, A., Zylicz, M. J. Biol. Chem. (2004) [Pubmed]
  19. Crystal structure and molecular modeling of 17-DMAG in complex with human Hsp90. Jez, J.M., Chen, J.C., Rastelli, G., Stroud, R.M., Santi, D.V. Chem. Biol. (2003) [Pubmed]
  20. Structural and quantum chemical studies of 8-aryl-sulfanyl adenine class Hsp90 inhibitors. Immormino, R.M., Kang, Y., Chiosis, G., Gewirth, D.T. J. Med. Chem. (2006) [Pubmed]
  21. Growth factors acting via tyrosine kinase receptors induce HSP90 alpha gene expression. Jérôme, V., Léger, J., Devin, J., Baulieu, E.E., Catelli, M.G. Growth Factors (1991) [Pubmed]
  22. SGT, a Hsp90beta binding partner, is accumulated in the nucleus during cell apoptosis. Yin, H., Wang, H., Zong, H., Chen, X., Wang, Y., Yun, X., Wu, Y., Wang, J., Gu, J. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  23. Phosphorylation analysis of 90 kDa heat shock protein within the cytosolic arylhydrocarbon receptor complex. Ogiso, H., Kagi, N., Matsumoto, E., Nishimoto, M., Arai, R., Shirouzu, M., Mimura, J., Fujii-Kuriyama, Y., Yokoyama, S. Biochemistry (2004) [Pubmed]
  24. Dimerization characteristics of the 94-kDa glucose-regulated protein. Nemoto, T., Matsusaka, T., Ota, M., Takagi, T., Collinge, D.B., Walther-Larsen, H. J. Biochem. (1996) [Pubmed]
  25. Participation of the lipoprotein receptor LRP1 in hypoxia-HSP90alpha autocrine signaling to promote keratinocyte migration. Woodley, D.T., Fan, J., Cheng, C.F., Li, Y., Chen, M., Bu, G., Li, W. J. Cell. Sci. (2009) [Pubmed]
  26. Regulation of Pim-1 by Hsp90. Mizuno, K., Shirogane, T., Shinohara, A., Iwamatsu, A., Hibi, M., Hirano, T. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  27. Interleukin-4 upregulates the heat shock protein Hsp90alpha and enhances transcription of a reporter gene coupled to a single heat shock element. Metz, K., Ezernieks, J., Sebald, W., Duschl, A. FEBS Lett. (1996) [Pubmed]
  28. Proteomic identification of heat shock protein 90 as a candidate target for p53 mutation reactivation by PRIMA-1 in breast cancer cells. Rehman, A., Chahal, M.S., Tang, X., Bruce, J.E., Pommier, Y., Daoud, S.S. Breast Cancer Res. (2005) [Pubmed]
  29. Differential induction of Hsp70-encoding genes in human hematopoietic cells. Leppä, S., Kajanne, R., Arminen, L., Sistonen, L. J. Biol. Chem. (2001) [Pubmed]
  30. Hsp90alpha recruited by Sp1 is important for transcription of 12(S)-lipoxygenase in A431 cells. Hung, J.J., Wu, C.Y., Liao, P.C., Chang, W.C. J. Biol. Chem. (2005) [Pubmed]
  31. Quantification of the nucleocytoplasmic distribution of wild type and modified proteins using confocal microscopy: interaction between 90-kDa heat shock protein (Hsp90 alpha) and glucocorticosteroid receptor (GR). Leclerc, P., Jibard, N., Meng, X., Schweizer-Groyer, G., Fortin, D., Rajkowski, K., Kang, K., Catelli, M.G., Baulieu, E.E., Cadepond, F. Exp. Cell Res. (1998) [Pubmed]
  32. Sequence features and phylogenetic analysis of the stress protein hsp90alpha in chinook salmon (Oncorhynchus tshawytscha), a poikilothermic vertebrate. Palmisano, A.N., Winton, J.R., Dickhoff, W.W. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  33. Purification and identification of secreted oxidative stress-induced factors from vascular smooth muscle cells. Liao, D.F., Jin, Z.G., Baas, A.S., Daum, G., Gygi, S.P., Aebersold, R., Berk, B.C. J. Biol. Chem. (2000) [Pubmed]
  34. Oligomeric forms of the 90-kDa heat shock protein. Nemoto, T., Sato, N. Biochem. J. (1998) [Pubmed]
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