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Subcellular and Subnuclear Trafficking of Steroid Receptors

  • Donald B. DeFranco
Part of the Progress in Gene Expression book series (PRGE)

Abstract

Many external signals affect cell physiology through alterations in gene expression. Cell surface receptors, once they have been activated by the binding of appropriate ligands, mobilize signal transduction cascades that may ultimately affect the activity of defined sets of transcription factors. Receptors for steroid hormones, in contrast, are soluble, intracellular proteins that function as transcription factors to directly regulate the transcriptional activity of target genes. Thus, steroid hormones utilize a streamlined signal transduction system in which a single protein, the steroid hormone receptor, has the capacity both to recognize an external signal and to transduce that signal to alterations in specific gene expression. The delivery of activated steroid receptors to genomic target sites must be efficient to account for the rapidity and selectivity of many transcriptional responses to steroid hormones. This review will focus on recent advances in subcellular trafficking of steroid receptors, and will include discussions both of receptor trafficking between different subcellular compartments (i.e., the cytoplasm and nucleus) and of the trafficking of receptors within a specific compartment (i.e., the nucleus).

Keywords

Glucocorticoid Receptor Steroid Receptor Nuclear Export Nuclear Matrix Nuclear Import 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Antakly T, and Eisen HJ (1984): Immunocytochemical localization of glucocorticoid receptors in target cells. Endocrinology 115: 1984–1989.CrossRefGoogle Scholar
  2. Barrack ER (1987): Localization of steroid receptors in the nuclear matrix. In: Steroid Hormone Receptors. Their Intracellular Localisation Clark CR, ed. Chichester (England): Ellis Horwood Ltd.Google Scholar
  3. Barrack ER, and Coffey DS (1980): The specific binding of estrogens and androgens to the nuclear matrix of sex responsive tissues. J. Biol. Chem. 255: 7265–7275.PubMedGoogle Scholar
  4. Berezney R (1991): The nuclear matrix: A heuristic model for investigating genomic organization and function in the cell nucleus. J. Cell. Biochem. 47: 109–123.PubMedCrossRefGoogle Scholar
  5. Bidwell JP, van Wijnen AJ, Fey AG, Dworetzky S, Penman S, Stein JL, Lian JB, and Stein GS (1993): Osteocalcin gene promoter-binding factors are tissue-specific nuclear matrix components. Proc. Natl. Acad. Sci. USA 90: 3162–3166.PubMedCrossRefGoogle Scholar
  6. Bohen SP, and Yamamoto KR (1994): Modulation of steroid receptor signal transduction by heat shock proteins. In: The Biology of Heat Shock Proteins and Molecular Chaperones Morimoto, RI, Tissieres, A, Georgopoulos, C, eds. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press.Google Scholar
  7. Cadepond F, Gasc JM, Delahaye F, Jibard N, Schweizer GG, Segard MI, Evans R, and Baulieu EE (1992): Hormonal regulation of the nuclear localization signals of the human glucocorticosteroid receptor. Exp. Cell Res. 201: 99–108.PubMedCrossRefGoogle Scholar
  8. Chandran UR, and DeFranco DB (1992): Internuclear migration of chicken progesterone receptor, but not simian virus-40 large tumor antigen, in transient heterokaryons. Mol. Endocrinol. 6: 837–844.PubMedCrossRefGoogle Scholar
  9. Colwill K, Pawson T, Andrews B, Prasad J, Manley JL, Bell JC, and Duncan PI (1996): The Clk/Sty protein kinase phosphorylates SR splicing factors and regulates their intranuclear distribution. EMBO J. 15: 265–275.PubMedGoogle Scholar
  10. Csermely P, Schnaider T, and Szanto I (1995): Signaling and transport through the nuclear membrane. Biochim. Biophys. Acta 1241: 425–452.PubMedCrossRefGoogle Scholar
  11. Dauvois S, White R, and Parker MG (1993): The antiestrogen ICI 182780 disrupts estrogen receptor nucleocytoplasmic shuttling. J. Cell Sci. 106: 1377–1388.PubMedGoogle Scholar
  12. DeFranco DB, Madan AP, Tang Y, Chandran UR, Xiao N, and Yang J (1995) Nucleocytoplasmic Shuttling of Steroid Receptors. In: Vitamins and Hormones Litwack, G, ed. New York: Academic Press.Google Scholar
  13. Dingwall C, and Laskey RA (1991): Nuclear targeting sequences—a consensus? TIBS 16: 478–481.PubMedGoogle Scholar
  14. Dworetzky SI, Wright KL, Fey EG, Penman S, Lian JB, Stein JL, and Stein GS (1992): Sequence-specific DNA binding proteins are components of a nuclear matrix attachment site. Proc. Natl. Acad. Sci. USA 89: 4178–4182.PubMedCrossRefGoogle Scholar
  15. Fischer U, Huber J, Boelens WC, Mattaj IW, and Luhrmann R (1995): The HIV-1 Rev activation domain is a nuclear export signal that accesses an export pathway used by specific cellular RNAs. Cell 82: 475–483.PubMedCrossRefGoogle Scholar
  16. Gasc J-M, Renoir J-M, Delahaye F, and Baulieu E-E (1990): Nuclear localization of two steroid receptor-associated proteins, hsp90 and p59. Exp. Cell Res. 186: 362–367.PubMedCrossRefGoogle Scholar
  17. Gasser SM, and Laemmli UK (1986): Cohabitation of scaffold binding regions with upstream/enhancer elements of three developmentally regulated Drosophila melanogaster genes. Cell 46: 521–530.PubMedCrossRefGoogle Scholar
  18. Georgopoulos C, and Welch WJ (1993): Role of the major heat shock proteins as molecular chaperones. Ann. Rev. Cell Biol. 9: 601–634.PubMedCrossRefGoogle Scholar
  19. Gerace L (1995): Nuclear export signals and the fast track to the cytoplasm. Cell 82: 341–344.PubMedCrossRefGoogle Scholar
  20. Getzenberg RH (1994): Nuclear matrix and the regulation of gene expression: tissue specificity. J. Cell. Biochem. 55: 22–31.PubMedCrossRefGoogle Scholar
  21. Getzenberg RH, and Coffey DS (1990): Tissue specificity of the hormonal response in sex accessory tissues is associated with nuclear matrix protein patterns. Mol. Endocrinol. 4: 1336–1342.PubMedCrossRefGoogle Scholar
  22. Görlich D, Prehn S, Laskey RA, and Hartmann E (1994): Isolation of a protein that is essential for the first step of nuclear protein import. Cell 79: 767–778.PubMedCrossRefGoogle Scholar
  23. Gorski J, Toft D, Shyamala G, Smith D, and Notides A (1968): Hormone receptors: studies on the interaction of estrogen with the uterus. Recent Prog. Hormone Res. 24: 45–80.Google Scholar
  24. Gui J-F, Lane WS, and Fu X-D (1994): A serine kinase regulates intracellular localization of splicing factors in the cell cycle. Nature 369: 678–682.PubMedCrossRefGoogle Scholar
  25. Guiochon-Mantel A, Delabre K, Lescop P, and Milgrom E (1994): Nuclear localization signals also mediate the outward movement of proteins from the nucleus. Proc. Natl. Acad. Sci. USA 91: 7179–7183.PubMedCrossRefGoogle Scholar
  26. Guiochon-Mantel A, Lescop P, Christin-Maitre S, Loosefelt H, Perrot-Applanat M, and Milgrom E (1991): Nucleocytoplasmic shuttling of the progesterone receptor. EMBO J. 10: 3851–3859.PubMedGoogle Scholar
  27. He D, Nickerson JA, and Penman S (1990): Core filaments of the nuclear matrix. J. Cell Biol. 110: 569–580.PubMedCrossRefGoogle Scholar
  28. Hendrick JP, and Hartl F-U (1993): Molecular chaperone functions of heat-shock proteins. Ann. Rev. Biochem. 62: 349–384.PubMedCrossRefGoogle Scholar
  29. Htun H, Barsony J, Renyi I, Gould DL, and Hager GL (1996): Visualization of glucocorticoid receptor translocation and intranuclear organization in living cells with a green fluorescent protein chimera. Proc. Natl. Acad. Sci. USA 93: 4845–4850.PubMedCrossRefGoogle Scholar
  30. Hu L-M, Bodwell J, Hu J-M, Orti E, and Munck A (1994): Glucocorticoid receptors in ATP-depleted cells. Dephosphorylation, loss of hormone binding, Hsp90 dissociation and ATP-dependent cycling. J. Biol. Chem. 269: 6571–6577.PubMedGoogle Scholar
  31. Huang S, and Spector DL (1996): Intron-dependent recruitment of pre-mRNA splicing factors to sites of transcription. J. Cell Biol. 133: 719–732.PubMedCrossRefGoogle Scholar
  32. Jensen EV, Suzuki T, Kawashima T, Stumpf WE, Jungblut PW, and DeSombre ER (1968): A two step mechanism for the interaction of estradiol with rat uterus. Proc. Natl. Acad. Sci. USA 59: 632–638.PubMedCrossRefGoogle Scholar
  33. Jenster G, Trapman J, and Brinkmann AO (1993): Nuclear import of the human androgen receptor. Biochem. J. 293: 761–768.PubMedGoogle Scholar
  34. Kang KI, Devin J, Cadepond F, Jibard N, Guiochon-Mantel A, Baulieu E-E, and Catelli M-G (1994): In vivo functional protein-protein interaction: Nuclear targeted hsp90 shifts cytoplasmic steroid receptor mutants into the nucleus. Proc. Natl. Acad. Sci. USA 91: 340–344.PubMedCrossRefGoogle Scholar
  35. Ktistaki E, Ktistakis NT, Papadogerogaki E, and Talianidis I (1995): Recruitment of hepatocyte nuclear factor 4 into specific intranuclear compartments depends on tyrosine phosphorylation that affects its DNA-binding and transactivation potential. Proc. Natl. Acad. Sci. USA 92: 9876–9880.PubMedCrossRefGoogle Scholar
  36. LaCasse EC, Lochnan HA, Walker P, and Lefebvre YA (1993): Identification of binding proteins for nuclear localization signals of the glucocorticoid and thyroid receptors. Endocrinology 132: 1017–1025.PubMedCrossRefGoogle Scholar
  37. Lombes M, Farman N, Oblin ME, Baulieu EE, Bonvalet JP, Erlanger BF, and Gasc JM (1990): Immunohistochemical localization of rat renal mineralocorticoid receptor by using an anti-idiotypic antibody that is an internal image of aldosterone. Proc. Natl. Acad. Sci. USA 87: 1086–1088.PubMedCrossRefGoogle Scholar
  38. Madan AP, and DeFranco DB (1993): Bidirectional transport of glucocorticoid receptors across the nuclear envelope. Proc. Natl. Acad. Sci. USA 90: 3588–3592.PubMedCrossRefGoogle Scholar
  39. Mancini MA, Shan B, Nickerson JA, Penman S, and Lee W-H (1994): The retinoblastoma gene product is a cell cycle-dependent, nuclear matrix-associated protein. Proc. Natl. Acad. Sci. USA 91: 418–422.PubMedCrossRefGoogle Scholar
  40. Mandell RB, and Feldherr CM (1990): Identification of two HSP70-related Xenopus oocyte proteins that are capable of recycling across the nuclear envelope. J. Cell Biol. 111: 1775–1783.PubMedCrossRefGoogle Scholar
  41. Mendel DB, Bodwell JE, and Munck A (1986): Glucocorticoid receptors lacking hormone-binding activity are bound in nuclei of ATP-depleted cells. Nature 324: 478–480.PubMedCrossRefGoogle Scholar
  42. Michael WM, Choi M, and Dreyfuss G (1995): A nuclear export signal in hnRNP Al: a signal-mediated, temperature-dependent nuclear protein export pathway. Cell 83: 415–422.PubMedCrossRefGoogle Scholar
  43. Mittnacht S, Lees JA, Desai D, Harlow E, Morgan DO, and Weinberg RA (1994): Distinct sub-populations of the retinoblastoma protein show a distinct pattern of phosphorylation. EMBO J. 13: 118–127.PubMedGoogle Scholar
  44. Mittnacht S, and Weinberg RA (1991): Gl/S phosphorylation of the retinoblastoma protein is associated with an altered affinity for the nuclear compartment. Cell 65: 381–393.PubMedCrossRefGoogle Scholar
  45. Moroianu J, and Blobel G (1995): Protein export from the nucleus requires the GTPase Ran and GTP hydrolysis. Proc. Natl. Acad. Sci. USA 92: 4318–4322.PubMedCrossRefGoogle Scholar
  46. Okuno Y, Imamoto N, and Yoneda Y (1993): 70-kDa heat-shock cognate protein colocalizes with karyophilic proteins into the nucleus during their transport in vitro. Exp. Cell Res. 206: 134–142.PubMedCrossRefGoogle Scholar
  47. Perrot-Applanat M, Groyer-Picard M-T, Logeat F, and Milgrom E (1986): Ultra-structural localization of the progesterone receptor by an immunogold method: effect of hormone administration. J. Cell Biol. 102: 1191–1199.PubMedCrossRefGoogle Scholar
  48. Perrot-Applanat M, Logeat F, Groyer-Picard MT, and Milgrom E (1985): Immunocytochemical study of mammalian progesterone receptor using monoclonal antibodies. Endocrinology 116: 1473–1484.PubMedCrossRefGoogle Scholar
  49. Picard D, and Yamamoto KR (1987): Two signals mediate hormone-dependent nuclear localization of the glucocorticoid receptor. EMBO J. 6: 3333–3340.PubMedGoogle Scholar
  50. Pollard VW, Michael WM, Nakielny S, Siomi MC, Wang F, and Dreyfuss G (1996): A novel receptor-mediated nuclear protein import pathway. Cell 86: 985–994.PubMedCrossRefGoogle Scholar
  51. Pratt WB (1993): The role of heat shock proteins in regulating the function, folding, and trafficking of the glucocorticoid receptor. J. Biol. Chem. 268: 21455–21458.PubMedGoogle Scholar
  52. Reik A, Schütz G, and Stewart AF (1991): Glucocorticoids are required for establishment and maintenance of an alteration in chromatin structure: induction leads to a reversible disruption of nucleosomes over an enhancer. EMBO J. 10: 2569–2576.PubMedGoogle Scholar
  53. Sackey FNA, Hache RJG, Reich T, Kwast-Welfeld J, and Lefebvre YA (1996): Determinants of subcellular distribution of the glucocorticoid receptor. Mol. Endocrinol. 10: 1191–1205.PubMedCrossRefGoogle Scholar
  54. Sanchez ER, Hirst M, Scherrer LC, Tang HY, Welsh MJ, Harmon JM, Simons SSJ, Ringold GM, and Pratt WB (1990): Hormone-free mouse glucocorticoid receptors overexpressed in Chinese hamster ovary cells are localized to the nucleus and are associated with both hsp70 and hsp90. J. Biol. Chem. 265: 20123–20130.PubMedGoogle Scholar
  55. Schmidt-Zachmann MS, Dargemont C, Kuhn LC, and Nigg EA (1993): Nuclear export of proteins: the role of nuclear retention. Cell 74: 493–504.PubMedCrossRefGoogle Scholar
  56. Schuchard M, Subramaniam M, Ruesink T, and Spelsberg TC (1991): Nuclear matrix localization and specific matrix DNA binding by Receptor Binding Factor-1 of the avian progesterone receptor. Biochemistry 30: 9516–9522.PubMedCrossRefGoogle Scholar
  57. Smith DF (1993): Dynamics of heat shock protein 90-progesterone receptor binding and the disactivation loop model for steroid receptor complexes. Mol. Endocrinol. 7: 1418–1429.PubMedCrossRefGoogle Scholar
  58. Smith DF, and Toft DO (1993): Steroid receptors and their associated proteins. Mol. Endocrinol. 7: 4–11.PubMedCrossRefGoogle Scholar
  59. Sommer L, Hagenbüchle O, Wellauer PK, and Strubin M (1991): Nuclear targeting of the transcription factor PTF 1 is mediated by a protein subunit that does not bind to the PTF1 cognate sequence. Cell 67: 987–994.PubMedCrossRefGoogle Scholar
  60. Spector DL (1993): Macromolecular domains within the cell nucleus. Ann. Rev. Cell Biol. 9: 265–315.PubMedCrossRefGoogle Scholar
  61. Stutz F, Neville M, and Rosbash M (1995): Identification of a novel nuclear pore-associated protein as a functional target of the HIV-1 Rev protein in yeast. Cell 82: 495–506.Google Scholar
  62. Sun J-M, Chen HY, and Davie JR (1994): Nuclear factor 1 is a component of the nuclear matrix. J. Cell. Biochem. 55: 252–263.PubMedCrossRefGoogle Scholar
  63. Tang Y, and DeFranco DB (1996): ATP-dependent release of glucocorticoid receptors from the nuclear matrix. Mol. Cell. Biol. 16: 1989–2001.PubMedGoogle Scholar
  64. Tang Y, and DeFranco DB (1996): ATP-dependent release of glucocorticoid receptors from the nuclear matrix. Mol. Cell. Biol. 16: 1989–2001.PubMedGoogle Scholar
  65. van Steensel B, Brink M, van der Meulen K, van Binnendijl EP, Wansink DG, de Jong L, de Kloet ER, and van Driel R (1995a): Localization of the glucocorticoid receptor in discrete clusters in the cell nucleus. J. Cell Sci. 108: 3003–3011.Google Scholar
  66. van Steensel B, Jenster G, Damm K, Brinkmann AO, and van Driel R (1995b): Domains of the human androgen receptor and glucocorticoid receptor involved in binding to the nuclear matrix. J. Cell. Biochem. 57: 465–478.CrossRefGoogle Scholar
  67. Van Wijnen AJ, Bidwell JP, Fey EG, Penman S, Lian JB, Stein JL, and Stein GS (1993): Nuclear matrix association of multiple sequence-specific DNA binding activities related to SP1, ATF, CCAAT, C/EBP, OCT-1, and AP-1. Biochemistry 32: 8397–8402.PubMedCrossRefGoogle Scholar
  68. Vasquez-Nin GH, Echeverria OM, Fakan S, Traish AM, Wotiz HH, and Martin TE (1991): Immunoelectron microscopic localization of estrogen receptor on premRNA containing constituents of rat uterine cell nuclei. Exp. Cell Res. 192: 396–404.CrossRefGoogle Scholar
  69. Welshons W, Lieberman ME, and Gorski J (1984): Nuclear localization of unoccupied estrogen receptors: cytochalasin enucleation of GH3 cells. Nature 307: 747–749.PubMedCrossRefGoogle Scholar
  70. Welshons WV, and Judy BM (1995): Nuclear vs translocating receptor models and the excluded middle. Endocrine 3: 1–4.PubMedCrossRefGoogle Scholar
  71. Wen W, Meinkoth JL, Tsien RY, and Taylor SS (1995): Identification of a signal for rapid export of proteins from the nucleus. Cell 82: 463–473.PubMedCrossRefGoogle Scholar
  72. Wikström A-C, Bakke O, Okret S, Bronnegard M, and Gustafsson JA (1987): Intracellular localization of the glucocorticoid receptor: evidence for cytoplasmic and nuclear localization. Endocrinology 120: 1232–1242.PubMedCrossRefGoogle Scholar
  73. Yang J, and DeFranco DB (1994): Differential roles of heat shock protein 70 in the in vitro nuclear import of glucocorticoid receptor and simian virus 40 large tumor antigen. Mol. Cell. Biol. 14: 5088–5098.PubMedGoogle Scholar
  74. Yang J, and DeFranco DB (1996): Assessment of glucocorticoid receptor-heat shock protein 90 interactions in vivo during nucleocytoplasmic trafficking. Mol. Endocrinol. 10: 3–13.PubMedCrossRefGoogle Scholar
  75. Ylikomi T, Bocquel MT, Berry M, Gronemeyer H, and Chambon P (1992): Cooperation of proto-signals for nuclear accumulation of estrogen and progesterone receptors. EMBO J. 11: 3681–3694.PubMedGoogle Scholar
  76. Zaret KS, and Yamamoto KR (1984): Hormonally induced alterations of chromatin structure in the polyadenylation and transcription termination regions of the chicken ovalbumin gene. Cell 38: 29–38.PubMedCrossRefGoogle Scholar
  77. Zhao L-J and Padmanabhan R (1988): Nuclear transport of Adenovirus DNA polymerase is facilitated by interaction with preterminal protein. Cell 55: 1005–1015.PubMedCrossRefGoogle Scholar
  78. Zhou Z-X, Sar M, Simental JA, Lane MV, and Wilson EM (1994): A ligand-dependent bipartite nuclear targeting signal in the human androgen receptor. J. Biol. Chem. 269: 13115–13123.PubMedGoogle Scholar

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© Springer Science+Business Media New York 1998

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  • Donald B. DeFranco

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