Molecular Chaperones in Health and Disease pp 111-138

Part of the Handbook of Experimental Pharmacology book series (HEP, volume 172)

Chaperoning of Glucocorticoid Receptors

  • W.B. Pratt
  • Y. Morishima
  • M. Murphy
  • M. Harrell

Abstract

A multiprotein hsp90/hsp70-based chaperone machinery functions as a ‘cradleto-grave’ system for regulating the steroid binding, trafficking and turnover of the glucocorticoid receptor (GR). In an ATP-dependent process where hsp70 and hsp90 act as essential chaperones and Hop, hsp40, and p23 act as nonessential co-chaperones, the machinery assembles complexes between the ligand binding domain of the GR and hsp90. During GR-hsp90 heterocomplex assembly, the hydrophobic ligand-binding cleft is opened to access by steroid, and subsequent binding of steroid within the cleft triggers a transformation of the receptor such that it engages in more dynamic cycles of assembly/disassembly with hsp90 that are required for rapid dynein-dependent translocation to the nucleus. Within the nucleus, the hsp90 chaperonemachinery plays a critical role both in GR movement to transcription regulatory sites and in the disassembly of regulatory complexes as the hormone level declines. The chaperone machinery also pays a critical role in stabilization of the GR to ubiquitylation and proteasomal degradation. The initial GR interaction with hsp70 appears to be critical for the triage between hsp90 heterocomplex assembly and preservation of receptor function vs CHIP-dependent ubiquitylation and proteasomal degradation. The hsp90 chaperone machinery is ubiquitous and functionally conserved among eukaryotes, and it is possible that all physiologically significant actions of hsp90 require the hsp70-dependent assembly of client protein-hsp90 heterocomplexes.

Keywords

Glucocorticoid receptor Hsp90 Hsp70 Immunophilins Dynein 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Ballinger CA, Connell P, Wu Y, Hu Z, Thompson LJ, Yin LY, Patterson C (1999) Identification of CHIP, a novel tetratricopeptide repeat-containing protein that interacts with heat shock proteins and negatively regulates chaperone functions. Mol Cell Biol 19:4535–4545PubMedGoogle Scholar
  2. Baumann CT, Lim CS, Hager GL (1999) Intracellular localization and trafficking of steroid receptors. Cell Biochem Biophys 31:119–127PubMedGoogle Scholar
  3. Bercovich B, Stancovski I, Mayer A, Blumenfeld N, Laszlo A, Schwartz AL, Ciechanover A (1997) Ubiquitin-dependent degradation of certain protein substrates in vitro requires the molecular chaperone hsc70. J Biol Chem 272:9002–9010PubMedGoogle Scholar
  4. Billecke SS, Bender AT, Kanelakis KC, Murphy PJM, Lowe ER, Kamada Y, Pratt WB, Osawa Y (2002) Hsp90 is required for heme binding and activation of apo-neuronal nitric-oxide synthase. J Biol Chem 277:20504–20509PubMedCrossRefGoogle Scholar
  5. Billecke SS, Draganov DI, Morishima Y, Murphy PJM, Dunbar AY, Pratt WB, Osawa Y (2004) The role of hsp90 in heme-dependent activation of apo-neuronal nitric-oxide synthase. J Biol Chem 279:30252–30258PubMedCrossRefGoogle Scholar
  6. Bohen SP (1998) Genetic and biochemical analysis of p23 and ansamycin antibiotics in the function of hsp90-dependent signaling proteins. Mol Cell Biol 18:3330–3339PubMedGoogle Scholar
  7. Bresnick EH, Dalman FC, Sanchez ER, Pratt WB (1989) Evidence that the 90-kDa heat shock protein is necessary for the steroid binding conformation of the L cell glucocorticoid receptor. J Biol Chem 264:4992–4997PubMedGoogle Scholar
  8. Brugge JS, Erikson E, Erikson RL (1981) The specific interaction of the Rous sarcoma virus transformed protein, pp60v-src, with two cellular proteins. Cell 25:363–372PubMedCrossRefGoogle Scholar
  9. Cadepond F, Schweizer-Groyer G, Segard-Maurel I, Jibard N, Hollenberg SM, Giguere V, Evans RM, Baulieu EE (1991) Heat shock protein 90 as a critical factor in maintaining glucocorticosteroid receptor in a nonfunctional state. J Biol Chem 266:5834–5841PubMedGoogle Scholar
  10. Caplan AJ, Langley E, Wilson EM, Vidal J (1995) Hormone-dependent transactivation by the human androgen receptor is regulated by a dnaJ protein. J Biol Chem 270:5251–5257PubMedGoogle Scholar
  11. Carrigan PE, Nelson GM, Roberts PJ, Stoffer J, Riggs DL, Smith DF (2004) Multiple domains of the co-chaperone Hop are important for hsp70 binding. J Biol Chem 279:16185–16193PubMedCrossRefGoogle Scholar
  12. Catelli MG, Binart N, Jung-Testas I, Renoir JM, Baulieu EE, Feramisco JR, Welch WJ (1985) The common 90-kd protein component of nontransformed “8S” steroid receptors is a heat-shock protein. EMBO J 4: 3131–3135PubMedGoogle Scholar
  13. Chang HCJ, Lindquist S (1994) Conservation of hsp90 macromolecular complexes in Saccharomyces cerevisiae. J Biol Chem 269:24983–24988PubMedGoogle Scholar
  14. Chang HCJ, Nathan DF, Lindquist S (1997) In vivo analysis of the hsp90 cochaperone Sti1 (p60). Mol Cell Biol 17:318–325PubMedGoogle Scholar
  15. Chen S, Prapapanich V, Rimerman RA, Honore B, Smith DF (1996) Interactions of p60, a mediator of progesterone receptor assembly, with heat shock proteins hsp90 and hsp70. Mol Endocrinol 10:682–693PubMedCrossRefGoogle Scholar
  16. Connell P, Ballinger CA, Jiang J, Wu Y, Thompson LJ, Hohfeld J, Patterson C (2001) The co-chaperone CHIP regulates protein triage decisions mediated by heat-shock proteins. Nature Cell Biol 3:93–96PubMedGoogle Scholar
  17. Cyr DM, Hohfeld J, Patterson C (2002) Protein quality control: U-box-containing E3 ubiquitin ligases join the fold. Trends Biochem Sci 27:368–375PubMedCrossRefGoogle Scholar
  18. Czar MJ, Owens-Grillo JK, Yem AW, Leach KL, Deibel MR, Welsh MJ, Pratt WB (1994) The hsp56 immunophilin component of untransformed steroid receptor complexes is localized both to microtubules in the cytoplasm and to the same nonrandom regions within the nucleus as the steroid receptor. Mol Endocrinol 8:1731–1741PubMedCrossRefGoogle Scholar
  19. Czar MJ, Galigniana MD, Silverstein AM, Pratt WB (1997) Geldanamycin, a heat shock protein 90-binding benzoquinone ansamycin, inhibits steroid-dependent translocation of the glucocorticoid receptor fromthe cytoplasm to the nucleus. Biochemistry 36:7776–7785PubMedCrossRefGoogle Scholar
  20. Davies TH, Ning YM, Sanchez ER (2002) A new first step in activation of steroid receptors. Hormone-induced switching of FKBP51 and FKBP52 immunophilins. J Biol Chem 277:4597–4600PubMedGoogle Scholar
  21. DeFranco DB, Madan AP, Tang Y, Chandran UR, Xiao N, Yang J (1995) Nuclear cytoplasmic shuttling of steroid receptors. Vitam Horm 51:315–338PubMedCrossRefGoogle Scholar
  22. DeFranco DB, Ramakrishnan C, Tang Y (1998) Molecular chaperones and subcellular trafficking of steroid receptors. J Steroid Biochem Mol Biol 65:51–58PubMedCrossRefGoogle Scholar
  23. Demand J, Alberti S, Patterson C, Hohfeld J (2001) Cooperation of a ubiquitin domain protein and an E3 ubiquitin ligase during chaperone/proteasome coupling. Curr Biol 11:1569–1577PubMedCrossRefGoogle Scholar
  24. Dittmar KD, Pratt WB (1997) Folding of the glucocorticoid receptor by the reconstituted hsp90-based chaperone machinery. The initial hsp90-p60-hsp70-dependent step is sufficient for creating the steroid binding conformation. J Biol Chem 272:13047–13054PubMedGoogle Scholar
  25. Dittmar KD, Hutchison KA, Owens-Grillo JK, Pratt WB (1996) Reconstitution of the steroid receptor-hsp90 heterocomplex assembly systemof rabbit reticulocyte lysate. J Biol Chem 271:12833–12839PubMedGoogle Scholar
  26. Dittmar KD, Demady DR, Stancato LF, Krishna P, Pratt WB (1997) Folding of the glucocorticoid receptor by the heat shock protein (hsp) 90-based chaperone machinery. The role of p23 is to stabilize receptor-hsp90 heterocomplexes formed by hsp90-p60-hsp70. J Biol Chem 272:21213–21220PubMedGoogle Scholar
  27. Dittmar KD, Banach M, Galigniana MD, Pratt WB (1998) The role of DnaJ-like proteins in glucocorticoid receptor-hsp90 heterocomplex assembly by the reconstituted hsp90-p60-hsp70 foldosome complex. J Biol Chem 273: 7358–7366PubMedCrossRefGoogle Scholar
  28. Dutta R, Inouye M (2000) GHKL, an emergent ATPase/kinase superfamily. Trends Biochem Sci 25:24–28PubMedCrossRefGoogle Scholar
  29. Elbi C, Walker DA, Romero G, Sullivan WP, Toft DO, Hager GL, DeFranco DB (2004) Molecular chaperones function as steroid receptor nuclear mobility factors. Proc Natl Acad Sci U S A 101:2876–2881PubMedCrossRefGoogle Scholar
  30. Freedman ND, Yamamoto KR (2004) Importin 7 and importin α/importin β are nuclear import receptors for the glucocorticoid receptor. Mol Biol Cell 15:2276–2286PubMedCrossRefGoogle Scholar
  31. Freeman BC, Yamamoto KR (2002) Disassembly of transcriptional regulatory complexes by molecular chaperones. Science 296:2232–2235PubMedCrossRefGoogle Scholar
  32. Galigniana MD, Scruggs JL, Herrington J, Welsh MJ, Carter-Su C, Housley PR, Pratt WB (1998) Heat shock protein 90-dependent (geldanamycin-inhibited) movement of the glucocorticoid receptor through the cytoplasm to the nucleus requires intact cytoskeleton. Mol Endocrinol 12:1903–1913PubMedCrossRefGoogle Scholar
  33. Galigniana MD, Radanyi C, Renoir JM, Housley PR, Pratt WB (2001) Evidence that the peptidylprolyl isomerase domain of the hsp90-binding immunophilin FKBP52 is involved in both dynein interaction and glucocorticoid receptor movement to the nucleus. J Biol Chem 276:14884–14889PubMedCrossRefGoogle Scholar
  34. Galigniana MD, Harrell JM, Murphy PJM, Chinkers M, Radanyi C, Renoir JM, Zhang M, Pratt WB (2002) Binding of hsp90-associated immunophilins to cytoplasmic dynein: direct binding and in vivo evidence that the peptidylprolyl isomerase domain is a dynein interaction domain. Biochemistry 41:13602–13610PubMedCrossRefGoogle Scholar
  35. Galigniana MD, Harrell JM, Housley PR, Patterson C, Fisher SK, Pratt WB (2004a) Retrograde transport of the glucocorticoid receptor in neurites requires dynamic assembly of complexes with the protein chaperone hsp90 and is linked to the CHIP component of the machinery for proteasomal degradation. Mol Brain Res 123:27–36PubMedCrossRefGoogle Scholar
  36. Galigniana MD, Harrell JM, O’Hagen HM, Ljungman M, Pratt WB (2004b) Hsp90-binding immunophilins link p53 to dynein during p53 transport to the nucleus. J Biol Chem 279:22483–22489PubMedGoogle Scholar
  37. Galigniana MD, Morishima Y, Gallay PA, Pratt WB (2004) Cyclophilin-A is bound through its peptidylprolyl isomerase domain to the cytoplasmic dynein motor protein complex. J Biol Chem 279:55754–55759; e-pub Oct 20, 2004PubMedGoogle Scholar
  38. Gee AC, Katzenellenbogen JA (2001) Probing conformational changes in the estrogen receptor: evidence for a partially unfolded intermediate facilitating ligand binding and release. Mol Endocrinol 15:421–428PubMedCrossRefGoogle Scholar
  39. Georget V, Terouanne B, Nicolas JC, Sultan C (2002) Mechanism of antiandrogen action: key role of hsp90 in conformational change and transcriptional activity of the androgen receptor. Biochemistry 41:11824–11831PubMedCrossRefGoogle Scholar
  40. Gething MJ, Sambrook J (1992) Protein folding in the cell. Nature 355:33–45PubMedCrossRefGoogle Scholar
  41. Giannoukos G, Silverstein AM, Pratt WB, Simons SS (1999) The seven amino acids (547-553) of rat glucocorticoid receptor required for steroid and hsp90 binding contain a functionally independent LXXLL motif that is critical for steroid binding. J Biol Chem 274:36527–36536PubMedCrossRefGoogle Scholar
  42. Grenert JP, Johnson BD, Toft DO (1999) The importance of ATP binding and hydrolysis by hsp90 in formation and function of protein heterocomplexes. J Biol Chem 274:17525–17533PubMedCrossRefGoogle Scholar
  43. Hager GL, Elbi C, Becker M (2002) Protein dynamics in the nuclear compartment. Curr Opin Genet Dev 12: 137–141PubMedCrossRefGoogle Scholar
  44. Han W, Christen P (2003) Mechanism of the targeting action of DnaJ in the DnaK molecular chaperone system. J Biol Chem 278:19038–19043PubMedGoogle Scholar
  45. Harrell JM, Kurek I, Breiman A, Radanyi C, Renoir JM, Pratt WB, Galigniana MD (2002) All of the protein interactions that link steroid receptor-hsp90-immunophilin heterocomplexes to cytoplasmic dynein are common to plant and animal cells. Biochemistry 41:5581–5587PubMedCrossRefGoogle Scholar
  46. Harrell JM, Murphy PJM, Morishima Y, Chen H, Mansfield JF, Galigniana MD, Pratt WB (2004) Evidence for glucocorticoid receptor transport on microtubules by dynein. J Biol Chem 279:54647–54654; e-pub Oct 13, 2004PubMedCrossRefGoogle Scholar
  47. Hernandez MP, Chadli A, Toft DO (2002a) Hsp40 binding is the first step in the hsp90 chaperoning pathway for the progesterone receptor. J Biol Chem 277:11873–11881Google Scholar
  48. Hernandez MP, Sullivan WP, Toft DO (2002b) The assembly and intermolecular properties of the hsp70-Hop-hsp90 molecular chaperone complex. J Biol Chem 277:38294–38304PubMedGoogle Scholar
  49. Hirokawa N (1998) Kinesin and dynein superfamily proteins and the mechanism of organelle transport. Science 279:519–526PubMedCrossRefGoogle Scholar
  50. Hohfeld J, Cyr DM, Patterson C (2001) From the cradle to the grave: molecular chaperones that may choose between folding and degradation. EMBO Rep 2:885–890PubMedCrossRefGoogle Scholar
  51. Htun H, Barsony J, Renyi I, Gould DL, Hager GL (1996) Visualization of glucocorticoid receptor translocation and intranuclear organization in living cellswith a green fluorescent protein chimera. Proc Natl Acad Sci U S A 93: 4845–4850PubMedCrossRefGoogle Scholar
  52. Hutchison KA, Czar MJ, Scherrer LC, Pratt WB (1992) Monovalent cation selectivity for ATP-dependent association of the glucocorticoid receptor with hsp70 and hsp90. J Biol Chem 267:14047–14053PubMedGoogle Scholar
  53. Hutchison KA, Dittmar KD, Czar MJ, Pratt WB (1994a) Proof that hsp70 is required for assembly of the glucocorticoid receptor into a heterocomplex with hsp90. J Biol Chem 269:5043–5049PubMedGoogle Scholar
  54. Hutchison KA, Dittmar KD, Pratt WB (1994b) All of the factors required for assembly of the glucocorticoid receptor into a functional heterocomplex with heat shock protein 90 are preassociated in a self-sufficient protein folding structure, a “foldosome”. J Biol Chem 269:27894–27899PubMedGoogle Scholar
  55. Jakob U, Lilie H, Meyer I, Buchner J (1995) Transient interaction of hsp90 with early unfolding intermediates of citrate synthase. J Biol Chem 270:7288–7294PubMedGoogle Scholar
  56. Jiang J, Ballinger CA, Wu Y, Dai Q, Cyr DM, Hohfeld J, Patterson C (2001) CHIP is a Ubox-dependent E3 ubiquitin ligase: identification of hsc70 as a target for ubiquitylation. J Biol Chem 276:42938–42944PubMedGoogle Scholar
  57. Johnson JL, Toft DO (1994) A novel chaperone complex for steroid receptors involving heat shock proteins, immunophilins, and p23. J Biol Chem 269:24989–24993PubMedGoogle Scholar
  58. Kanelakis KC, Morishima Y, Dittmar KD, Galigniana MD, Takayama S, Reed JC, Pratt WB (1999) Differential effects of the hsp70-binding proteinBAG-1 on glucocorticoid receptor folding by the hsp90-based chaperone machinery. J Biol Chem 274:34134–34140PubMedCrossRefGoogle Scholar
  59. Kanelakis KC, Murphy PJM, Galigniana MD, Morishima Y, Takayama S, Reed JC, Toft DO, Pratt WB (2000) hsp70 interacting protein Hip does not affect glucocorticoid receptor folding by the hsp90-based chaperone machinery except to oppose the effect of BAG-1. Biochemistry 39:14314–14321PubMedCrossRefGoogle Scholar
  60. Kanelakis KC, Shewach DS, Pratt WB (2002) Nucleotide binding states of hsp70 and hsp90 during sequential steps in the process of glucocorticoid receptor-hsp90 heterocomplex assembly. J Biol Chem 277:33698–33703PubMedCrossRefGoogle Scholar
  61. Kang KI, Devin J, Cadepond F, Jibard N, Guiochon-Mantel A, Baulieu EE, Catelli MG (1994) In vivo functional protein-protein interaction: nuclear targeted hsp90 shifts cytoplasmic steroid receptor mutants into the nucleus. Proc Natl Acad Sci U S A 91:340–344PubMedGoogle Scholar
  62. Kaul S, Murphy PJM, Chen J, Brown L, Pratt WB, Simons SS (2002) Mutations at positions 547-553 of rat glucocorticoid receptors reveal that hsp90 binding requires the presence, but not defined composition, of a seven-amino acid sequence at the amino terminus of the ligand binding domain. J Biol Chem 277:36223–36232PubMedGoogle Scholar
  63. Kazlauskas A, Poellinger L, Pongratz I (2000) The immunophilin-like protein XAP2 regulates ubiquitination and subcellular localization of the dioxin receptor. J Biol Chem 275:41317–41324PubMedCrossRefGoogle Scholar
  64. Kazlauskas A, Sundstrom S, Poellinger L, Pongratz I (2001) The hsp90 chaperone complex regulates intracellular localization of the dioxin receptor. Mol Cell Biol 21:2594–2607PubMedCrossRefGoogle Scholar
  65. Kimura Y, Yahara I, Lindquist S (1995) Role of the protein chaperone YDJ1 in establishing hsp90-mediated signal transduction pathways. Science 268:1362–1365PubMedGoogle Scholar
  66. Kosano H, Stensgard B, Charlesworth MC, McMahon N, Toft DO (1998) The assembly of progesterone receptor-hsp90 complexes using purified proteins. J Biol Chem 273:32973–32979PubMedCrossRefGoogle Scholar
  67. Kost SL, Smith DF, Sullivan WP, Welch WJ, Toft DO (1989) Binding of heat shock proteins to the avian progesterone receptor. Mol Cell Biol 9:3829–3838PubMedGoogle Scholar
  68. Langer T, Lu C, Echols H, Flanagan J, Hayer MK, Hartl FU (1992) Successive action of DnaK, DnaJ and GroEL along the pathway of chaperone-mediated protein folding. Nature 356:683–689PubMedCrossRefGoogle Scholar
  69. Liu J, DeFranco DB (1999) Chromatin recycling of glucocorticoid receptors: implications for multiple roles of heat shock protein 90. Mol Endocrinol 13:355–365PubMedCrossRefGoogle Scholar
  70. Luders J, Demand J, Hohfeld J (2000) The ubiquitin-related BAG-1 provides a link between the molecular chaperones Hsc70/Hsp70 and the proteasome. J Biol Chem 275:4613–4617PubMedGoogle Scholar
  71. McLaughlin SH, Smith HW, Jackson SE (2002) Stimulation of the weak ATPase activity of human hsp90 by a client protein. J Mol Biol 315:787–798PubMedCrossRefGoogle Scholar
  72. McNally JG, Muller WG, Walker D, Wolford R, Hager GL (2000) The glucocorticoid receptor: rapid exchange with regulatory sites in living cells. Science 287:1262–1265PubMedCrossRefGoogle Scholar
  73. Minami Y, Hohfeld J, Ohtsuka K, Hartl FU (1996) Regulation of the heat-shock protein 70 reaction cycle by the mammalian DnaJ homolog, hsp40. J Biol Chem 271:19617–19624PubMedCrossRefGoogle Scholar
  74. Modarress KJ, Opoku J, Xu M, Sarlis NJ, Simons SS (1997) Steroid-induced conformational changes at ends of the hormone-binding domain in the rat glucocorticoid receptor are independent of agonist versus antagonist activity. J Biol Chem 272:23986–23994PubMedCrossRefGoogle Scholar
  75. Morishima Y, Kanelakis KC, Murphy PJM, Shewach DS, Pratt WB (2001) Evidence for iterative ratcheting of receptor-bound hsp70 between its ATP and ADP conformations during assembly of glucocorticoid receptor-hsp90 heterocomplexes. Biochemistry 40:1109–1116PubMedCrossRefGoogle Scholar
  76. Morishima Y, Kanelakis KC, Silverstein AM, Dittmar KD, Estrada L, Pratt WB (2000a) The hsp organizer protein Hop enhances the rate of but is not essential for glucocorticoid receptor folding by the multiprotein hsp90-based chaperone system. J Biol Chem 275:6894–6900PubMedGoogle Scholar
  77. Morishima Y, Murphy PJM, Li DP, Sanchez ER, Pratt WB (2000b) Stepwise assembly of a glucocorticoid receptor-hsp90 heterocomplex resolves two sequential ATP-dependent events involving first hsp70 and then hsp90 in opening of the steroid binding pocket. J Biol Chem 275:18054–18060PubMedGoogle Scholar
  78. Morishima Y, Kanelakis KC, Murphy PJM, Lowe ER, Jenkins GJ, Osawa Y, Sunahara RK, Pratt WB (2003) The hsp90 cochaperone p23 is the limiting component of the multiprotein hsp90/hsp70-based chaperone systemin vivo where it acts to stabilize the client protein-hsp90 complex. J Biol Chem 278:48754–48763PubMedGoogle Scholar
  79. Murphy PJM, Kanelakis KC, Galigniana MD, Morishima Y, Pratt WB (2001) Stoichiometry, abundance, and functional significance of the hsp90/hsp70-based multiprotein chaperone machinery in reticulocyte lysate. J Biol Chem 276: 30092–30098PubMedGoogle Scholar
  80. Murphy PJM, Morishima Y, Chen H, Galigniana MD, Mansfield JF, Simons SS, Pratt WB (2003) Visualization and mechanism of assembly of a glucocorticoid receptor-hsp70 complex that is primed for subsequent hsp90-dependent opening of the steroid binding cleft. J Biol Chem 278:34764–34773PubMedGoogle Scholar
  81. Nathan DF, Lindquist S (1995) Mutational analysis of Hsp90 function: interactions with a steroid receptor and a protein kinase. Mol Cell Biol 15:3917–3925PubMedGoogle Scholar
  82. Neckers L, Schulte TW, Mimnaugh E (1999) Geldanamycin as a potential anti-cancer agent: its molecular target and biochemical activity. Invest New Drugs 17:361–373PubMedCrossRefGoogle Scholar
  83. Nelson GM, Prapapanich V, Carrigan PE, Roberts PJ, Riggs DL, Smith DF (2004) The heat shock protein 70 cochaperone Hip enhances functional maturation of glucocorticoid receptor. Mol Endocrinol 18:1620–1630PubMedCrossRefGoogle Scholar
  84. Nishi M, Ogawa H, Ito T, Matsuda KI, Kawata M (2001) Dynamic changes in subcellular localization of mineralocorticoid receptor in living cells: in comparison with glucocorticoid receptor using dual-color labeling with green fluorescent protein spectral variants. Mol Endocrinol 15:1077–1092PubMedCrossRefGoogle Scholar
  85. O’Brien MC, McKay DB (1995) How potassium affects the activity of the molecular chaperone Hsc70. I. Potassium is required for optimal ATPase activity. J Biol Chem 270:2247–2250PubMedGoogle Scholar
  86. Oppermann H, Levinson W, Bishop JM (1981) A cellular protein that associates with the transforming protein of Rous sarcoma virus is also a heat-shock protein. Proc Natl Acad Sci U S A 78:1067–1071PubMedGoogle Scholar
  87. Owens-Grillo JK, Hoffmann K, Hutchison KA, Yem AW, Deibel MR, Handschumacher RE, Pratt WB (1995) The cyclosporin A-binding immunophilin CyP-40 and the FK506-binding immunophilin hsp56 bind to a common site on hsp90 and exist in independent cytosolic heterocomplexes with the untransformed glucocorticoid receptor. J Biol Chem 270: 20479–20484PubMedGoogle Scholar
  88. Oxelmark E, Knoblauch R, Arnal S, Su LF, Schapira M, Garabedian MJ (2003) Genetic dissection of p23, an hsp90 cochaperone, reveals a distinct surface involved in estrogen receptor signaling. J Biol Chem 278:36547–36555PubMedCrossRefGoogle Scholar
  89. Panaretou B, Siligardi G, Meyer P, Maloney A, Sullivan JK, Singh S, Millson SH, Clarke PA, Naaby-Hansen S, Stein R, Cramer R, Mollapour M, Workman P, Piper PW, Pearl LH, Prodromou C (2002) Activation of the ATPase activity of hsp90 by the stress-regulated cochaperone Aha1. Mol Cell 10:1307–1318PubMedCrossRefGoogle Scholar
  90. Picard D (1993) Steroid-binding domains for regulating the functions of heterologous proteins in cis. Trends Cell Biol 3:278–280PubMedCrossRefGoogle Scholar
  91. Picard D, Khursheed B, Garabedian MJ, Fortin MG, Lindquist S, Yamamoto KR (1990) Reduced levels of hsp90 compromise steroid receptor action in vivo. Nature 348:166–168PubMedCrossRefGoogle Scholar
  92. Pickart CM (2004) Back to the future with ubiquitin. Cell 116:181–190PubMedCrossRefGoogle Scholar
  93. Prapapanich V, Chen S, Smith DF (1998) Mutation of Hip’s carboxy-terminal region inhibits a transitional stage of progesterone receptor assembly. Mol Cell Biol 18:944–952PubMedGoogle Scholar
  94. Pratt WB (1993) The role of heat shock proteins in regulating the function, folding, and trafficking of the glucocorticoid receptor. J Biol Chem 268:21455–21458PubMedGoogle Scholar
  95. Pratt WB, Toft DO (1997) Steroid receptor interactions with heat shock protein and immunophilin chaperones. Endocr Rev 18:306–360PubMedCrossRefGoogle Scholar
  96. Pratt WB, Toft DO (2003) Regulation of signaling protein function and trafficking by the hsp90/hsp70-based chaperone machinery. Exp Biol Med 228:111–133Google Scholar
  97. Pratt WB, Jolly DJ, Pratt DV, Hollenberg SM, Giguere V, Cadepond FM, Schweizer-Groyer G, Catelli MG, Evans RM, Baulieu EE (1988) A region in the steroid binding domain determines formation of the non-DNA-binding, 9 S glucocorticoid receptor complex. J Biol Chem 263:267–273PubMedGoogle Scholar
  98. Pratt WB, Galigniana MD, Harrell JM, DeFranco DB (2004) Role of hsp90 and the hsp90-binding immunophilins in signaling protein movement. Cell Signal 16:857–872PubMedCrossRefGoogle Scholar
  99. Prodromou C, Roe SM, O’Brien R, Ladbury JE, Piper PW, Pearl LH (1997) Identification and structural characterization of the ATP/ADP-binding site in the hsp90 molecular chaperone. Cell 90:65–75PubMedCrossRefGoogle Scholar
  100. Renoir JM, Mercier-Bodard C, Hoffmann K, Le Bihan S, Ning YM, Sanchez ER, Handschumacher RE, Baulieu EE (1995) Cyclosporin A potentiates the dexamethasone-induced mouse mammary tumor virus-chloramphenicol acetyltransferase activity in LMCAT cells: a possible role for different heat shock protein-binding immunophilins in glucocorticosteroid receptor-mediated gene expression. Proc Natl Acad Sci U S A 92:4977–4981PubMedGoogle Scholar
  101. Riggs DL, Roberts PJ, Chirillo SC, Cheung-Flynn J, Prapapanich V, Ratajczak T, Gaber R, Picard D, Smith DF (2003) The hsp90-binding peptidylprolyl isomerase FKBP52 potentiates glucocorticoid signaling in vivo. EMBO J 22: 1158–1167PubMedCrossRefGoogle Scholar
  102. Sanchez ER, Toft DO, Schlesinger MJ, Pratt WB (1985) Evidence that the 90-kDa phosphoprotein associated with the untransformed L-cell glucocorticoid receptor is a murine heat-shock protein. J Biol Chem 260:12398–12401PubMedGoogle Scholar
  103. Sanchez ER, Meshinchi S, Tienrungroj W, Schlesinger MJ, Toft DO, Pratt WB (1987) Relationship of the 90-kDamurine heat shock protein to the untransformed and transformed states of the L cell glucocorticoid receptor. J Biol Chem 262:6986–6991PubMedGoogle Scholar
  104. Sanchez ER, Faber LE, Henzel WJ, Pratt WB (1990) The 56-59-kilodalton protein identified in untransformed steroid receptor complexes is a unique protein that exists in cytosol in a complex with both the 70-and 90-kilodalton heat shock proteins. Biochemistry 29:5145–5152PubMedGoogle Scholar
  105. Savory JGA, Hsu B, Laquian IR, Giffin W, Reich T, Hache RJG, Lefebvre YA (1999) Discrimination between NL1-and NL2-mediated nuclear localization of the glucocorticoid receptor. Mol Cell Biol 19:1025–1037PubMedGoogle Scholar
  106. Scherrer LC, Dalman FC, Massa E, Meshinchi S, Pratt WB (1990) Structural and functional reconstitution of the glucocorticoid receptor-hsp90 complex. J Biol Chem 265:21397–21400PubMedGoogle Scholar
  107. Scherrer LC, Hutchison KA, Sanchez ER, Randall SK, Pratt WB (1992) A heat shock protein complex isolated from rabbit reticulocyte lysate can reconstitute a functional glucocorticoid receptor-hsp90 complex. Biochemistry 31: 7325–7329PubMedGoogle Scholar
  108. Scherrer LC, Picard D, Massa E, Harmon JM, Simons SS, Yamamoto, KR, Pratt WB (1993) Evidence that the hormone binding domain of steroid receptors confers hormonal control on chimeric proteins by determining their hormone-regulated binding to heat-shock protein 90. Biochemistry 32:5381–5386PubMedCrossRefGoogle Scholar
  109. Schmidt U, Wochnik GM, Rosenhagen MC, Young JC, Hartl FU, Holsboer F, Rein T (2003) Essential role of the unusual DNA-binding motif of BAG-1 for inhibition of the glucocorticoid receptor. J Biol Chem 278:4926–4931PubMedGoogle Scholar
  110. Schneikert J, Hubner S, Langer G, Petri T, Jaattela M, Reed J, Cato ACB (2000) Hsp70-RAP46 interaction in downregulation of DNA binding by glucocorticoid receptor. EMBO J 19:6508–6516PubMedCrossRefGoogle Scholar
  111. Schowalter DB, Sullivan WP, Maihle NJ, Dobson ADW, Conneely OM, O’Malley BW, Toft DO (1991) Characterization of progesterone receptor binding to the 90-and 70-kDa heat shock proteins. J Biol Chem 266: 21165–21173PubMedGoogle Scholar
  112. Schuh S, Yonemoto W, Brugge J, Bauer VJ, Riehl RM, Sullivan WP, Toft DO (1985) A 90,000-dalton binding protein common to both steroid receptors and the Rous sarcoma virus transforming protein, pp60v-src. J Biol Chem 260:14292–14296PubMedGoogle Scholar
  113. Segnitz B, Gehring U (1997) The function of steroid hormone receptors is inhibited by the hsp90-specific compound geldanamycin. J Biol Chem 272:18694–18701PubMedCrossRefGoogle Scholar
  114. Sepp-Lorenzino L, Ma Z, Lebwohl DE, Vinitsky A, Rosen N (1995) Herbimycin A induces the 20 S proteasome-and ubiquitin-dependent degradation of receptor tyrosine kinases. J Biol Chem 270:16580–16587PubMedGoogle Scholar
  115. Silverstein AM, Galigniana MD, Chen MS, Owens-Grillo JK, Chinkers M, Pratt WB (1997) Protein phosphatase 5 is a major component of glucocorticoid receptor-hsp90 complexes with properties of an FK506-binding immunophilin. J Biol Chem 272:16224–16230PubMedGoogle Scholar
  116. Silverstein AM, Galigniana MD, Kanelakis KC, Radanyi C, Renoir JM, Pratt WB (1999) Different regions of the immunophilin FKBP52 determine its association with the glucocorticoid receptor, hsp90, and cytoplasmic dynein. J Biol Chem 274:36980–36986PubMedCrossRefGoogle Scholar
  117. Smith DF (1993) Dynamics of heat shock protein 90-progesterone receptor binding and the disactivation loop model for steroid receptor complexes. Mol Endocrinol 7:1418–1429PubMedGoogle Scholar
  118. Smith DF, Schowalter DB, Kost SL, Toft DO (1990) Reconstitution of progesterone receptor with heat shock proteins. Mol Endocrinol 4:1704–1711PubMedCrossRefGoogle Scholar
  119. Smith DF, Stensgard BA, Welch WJ, Toft DO (1992) Assembly of progesterone receptor with heat shock proteins and receptor activation are ATP mediated events. J Biol Chem 267:1350–1356PubMedGoogle Scholar
  120. Smith DF, Sullivan WP, Marion TN, Zaitsu K, Madden B, McCormick DJ, Toft DO (1993) Identification of a 60-kilodalton stress-related protein, p60, which interacts with hsp90 and hsp70. Mol Cell Biol 13:869–876PubMedGoogle Scholar
  121. Stancato LF, Silverstein AM, Gitler C, Groner B, Pratt WB (1996) Use of the thiol-specific derivatizing agent N-iodoacetyl-3-[125I]iodotyrosine to demonstrate conformational differences between the unbound and hsp90-bound glucocorticoid receptor hormone binding domain. J Biol Chem 271:8831–8836PubMedGoogle Scholar
  122. Stavreva DA, Muller WG, Hager GL, Smith CL, McNally JG (2004) Rapid glucocorticoid receptor exchange at a promoter is coupled to transcription and regulated by chaperones and proteasomes. Mol Cell Biol 24:2682–2697PubMedCrossRefGoogle Scholar
  123. Stebbins CE, Russo AA, Schneider C, Rosen N, Hartl FU, Pavletich NP (1997) Crystal structure of an Hsp90-geldanamycin complex: targeting of a protein chaperone by an antitumor agent. Cell 89:239–250PubMedCrossRefGoogle Scholar
  124. Sullivan W, Stensgard B, Caucutt G, Bartha B, McMahon N, Alnemri ES, Litwack G, Toft D (1997) Nucleotides and two functional states of hsp90. J Biol Chem 272:8007–8012PubMedCrossRefGoogle Scholar
  125. Szabo A, Langer T, Schroder H, Flanagan J, Bukau B, Hartl FU (1994) The ATP hydrolysis-dependent reaction cycle of the Escherichia coli hsp70 systemε-DnaK, DnaJ, and GrpE. Proc Natl Acad Sci U S A 91: 10345–10349PubMedGoogle Scholar
  126. Tanaka M, Nishi M, Morimoto M, Sugimoto T, Kawata M (2003) Yellow fluorescent protein-tagged and cyan fluorescent protein-tagged imaging analysis of glucocorticoid receptor and importins in single living cells. Endocrinology 144:4070–4079PubMedCrossRefGoogle Scholar
  127. Thomas M, Dadgar N, Aphale A, Harrell JM, Kunkel R, Pratt WB, Lieberman AP (2004) Androgen receptor acetylation site mutations cause trafficking defects, misfolding, and aggregation similar to expanded glutamine tracts. J Biol Chem 279:8389–8395PubMedGoogle Scholar
  128. Whitesell L, Cook P (1996) Stable and specific binding of heat shock protein 90 by geldanamycin disrupts glucocorticoid receptor function in intact cells. Mol Endocrinol 10:705–712PubMedCrossRefGoogle Scholar
  129. Whitesell L, Mimnaugh EG, De Costa B, Myers CE, Neckers LM (1994) Inhibition of heat shock protein HSP90-pp60v-src heteroprotein complex formation by benzoquinone ansamycins: essential role for stress proteins in oncogenic transformation. Proc Natl Acad Sci U S A 91:8324–8328PubMedGoogle Scholar
  130. Wiech H, Buchner J, Zimmermann R, Jakob U (1992) Hsp90 chaperones protein folding in vitro. Nature 358: 169–170PubMedCrossRefGoogle Scholar
  131. Wochnik GM, Young JC, Schmidt U, Holsboer F, Hartl FU, Rein T (2004) Inhibition of GR-mediated transcription by p23 requires interaction with hsp90. FEBS Lett 560:35–38PubMedCrossRefGoogle Scholar
  132. Xu M, Chakraborti PK, Garabedian MJ, Yamamoto KR, Simons SS (1996) Modular structure of glucocorticoid receptor domains is not equivalent to functional independence. J Biol Chem 271:21430–21438PubMedGoogle Scholar
  133. Xu M, Dittmar KD, Giannoukos G, Pratt WB, Simons SS (1998) Binding of hsp90 to the glucocorticoid receptor requires a specific 7-amino acid sequence at the amino terminus of the hormone-binding domain. J Biol Chem 273: 13918–13924PubMedGoogle Scholar
  134. Yang J, Liu J, DeFranco DB (1997) Subnuclear trafficking of glucocorticoid receptors in vitro: chromatin recycling and nuclear export. J Cell Biol 137:523–538PubMedGoogle Scholar
  135. Zeiner M, Gehring U (1995) A protein that interacts with members of the nuclear hormone receptor family: identification and cDNA cloning. Proc Natl Acad Sci U S A 92:11465–11469PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2006

Authors and Affiliations

  • W.B. Pratt
    • 1
  • Y. Morishima
    • 1
  • M. Murphy
    • 1
  • M. Harrell
    • 1
  1. 1.Department of PharmacologyUniversity of Michigan Medical SchoolAnn ArborUSA

Personalised recommendations