Skip to main content
Log in

Role of chaperones in nuclear translocation and transactivation of steroid receptors

  • Review
  • Published:
Endocrine Aims and scope Submit manuscript

Abstract

Molecular chaperones assist proteins to reach their mature and functional conformation. It has become apparent in recent years that chaperones function as part of a multiprotein heterocomplex that is potentially involved not only in protein folding, but also in intracellular trafficking and in targeting proteins for degradation. In the case of steroid receptors, the activity of the chaperone heterocomplex, as well as the proteins comprising the heterocomplex, has an effect on the observed ligand-dependent transcriptional activity of the receptor. The direct interaction between chaperones and steroid receptors makes them potential therapeutic targets in a number of pathologic conditions. In the case of cancers with steroid receptor involvement, such as breast and prostate cancer, the inhibition of chapterone activity may inhibit tumor cell growth. Conversely, enhancement of chaperone activity may be beneficial in disorders of protein misfolding, as in the case of androgen receptor aggregates found in Spinal and Bulbar Muscular Atrophy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Hartl, F. U. (1996). Nature 381, 571–580.

    Article  PubMed  CAS  Google Scholar 

  2. Beissinger, M., and Buchner, J. (1998). Biol. Chem. 379, 245–259.

    PubMed  CAS  Google Scholar 

  3. Smith, D. F. (2000). Seminars Cell Dev. Biol. 11, 45–52.

    Article  Google Scholar 

  4. Pratt, W. B., Silverstein, A. M., and Galigniana, M. D. (1999). Cellular Signalling 11, 839–851.

    Article  PubMed  CAS  Google Scholar 

  5. Welch, W. J. and Feramisco, J. R. (1982). J. Biol. Chem. 257, 14,949–14,559.

    CAS  Google Scholar 

  6. Ylikomi, T., Wurtz, J.-M., Syala, H., Passinen, A., Haverinen, M., Blauer, M., Tuohimaa, P., and Gronemeyer, H. (1998). Crit. Rev. Biochem. Mol. Biol. 33, 437–466.

    Article  PubMed  CAS  Google Scholar 

  7. Parsell, D. A. and Lindquist, S. (1993). Ann. Rev. Genet. 27, 437–496.

    Article  PubMed  CAS  Google Scholar 

  8. Voss, A. K., Thomas, T., and Gruss, P. (2000). Development 127, 1–11.

    PubMed  CAS  Google Scholar 

  9. Pratt, W. B. (1997). Annu. Rev. Pharmacol. Toxicol. 37, 297–326.

    Article  PubMed  CAS  Google Scholar 

  10. Wright, L. S., Finn, K. A., and Siegel, F. L. (1993). Prot. Exp. Purif. 4, 417–424.

    Article  CAS  Google Scholar 

  11. Stancato, L. F., Chow, Y. H., Hutchison, K. A., Perdew, G. H., Jove, R., and Pratt, W. B. (1993). J. Biol. Chem. 268, 21,711–21,716.

    CAS  Google Scholar 

  12. Hutchinson, K. A., Brott, B. K., DeLeon, J. H., Perdew, G. H., Jove, R., and Pratt, W. B. (1992). J. Biol. Chem. 267, 2902–2908.

    Google Scholar 

  13. Nathan, D. F. and Lindquist, S. (1995). Mol. Cell. Biol. 15, 3917–3925.

    PubMed  CAS  Google Scholar 

  14. Matts, R. L. and Hurst, R. (1989). J. Biol. Chem. 264, 15,542–15,547.

    CAS  Google Scholar 

  15. Miyata, Y. and Yahara, I. (1992). J. Biol. Chem. 267, 7042–7047.

    PubMed  CAS  Google Scholar 

  16. Pratt, W. B. and Toft, D. O. (1997). Endocr. Rev. 18, 306–360.

    Article  PubMed  CAS  Google Scholar 

  17. Reynolds, P. D., Ruan, Y., Smith, D. F., and Scammell, J. G. (1999). J. Clin. Endocrinol. Metab. 84, 663–669.

    Article  PubMed  CAS  Google Scholar 

  18. Morishima, Y., Kanelakis, K. C., Silverstein, A. M., Dittmar, K. D., Estrada, L., and Pratt, W. B. (2000). J. Biol. Chem. 275, 6894–6900.

    Article  PubMed  CAS  Google Scholar 

  19. Holley, S. J. and Yamamoto, K. R. (1995). Mol. Biol. Cell 6, 1833–1842.

    PubMed  CAS  Google Scholar 

  20. Kosano, H., Stensgard, B., Charlesworth, M. C., McMahon, N., and Toft, D. (1998). J. Biol. Chem. 273, 32,973–32,979.

    Article  CAS  Google Scholar 

  21. Smith, D. F. (1993). Mol. Endocrinol. 7, 1418–1429.

    Article  PubMed  CAS  Google Scholar 

  22. Johnson, B. D., Schmacher, R. J., Ross, E. D., and Toft, D. O. (1998). J. Biol. Sci. 273, 3679–3686.

    CAS  Google Scholar 

  23. Takayama, S., Bimston, N. N., Matsuzawa, S., Freeman, B. C., Aime-Simpe, C., Xie, Z., Morimoto, R. I., and Reed, J. C. (1997). EMBO J. 16, 4887–4896.

    Article  PubMed  CAS  Google Scholar 

  24. Hohfeld, J. and Jentsch, S. (1997). EMBO J. 16, 6209–6216.

    Article  PubMed  CAS  Google Scholar 

  25. Picard, D., Khursheed, B., Garabedian, M. J., Fortin, M. G., Lindquist, S., and Yamamoto, K. R. (1990). Nature 348, 166–168.

    Article  PubMed  CAS  Google Scholar 

  26. Cadepond, F., Schweizer-Groyer, G., Segard-Maurel, I., Jibard, N., Hollenberg, S. M., Giguere, V., Evans, R. M., and Baulieu, E.-E. (1991). J. Biol. Chem. 266, 5834–5841.

    PubMed  CAS  Google Scholar 

  27. Carson-Jurica, M. A., Lee, A. T., Dobson, A. W., Conneely, O. M., Schrader, W. T., and O’Malley, B. W. (1989). J. Steroid Biochem. 34, 1–6.

    Article  PubMed  CAS  Google Scholar 

  28. Chambraud, B., Berry, M., Redeuilh, G., Chambon, P., and Baulieu, E.-E. (1990). J. Biol. Chem. 265, 20,686–20,691.

    CAS  Google Scholar 

  29. Shiau, A. K., Barstad, D., Loria, P. M., Cheng, L., Kushner, P. J., Agard, D. A., and Greene, G. L. (1998). Cell 95, 927–937.

    Article  PubMed  CAS  Google Scholar 

  30. Brzozowski, A. M., Pike, A. C., Dauter, Z., Hubbard, R. E., Bonn, T., Engelstrom, O., Ohman, L., Greene, G. L., Gustafsson, J.-A., and Carlquist, M. (1997). Nature 389, 753–758.

    Article  PubMed  CAS  Google Scholar 

  31. Bohen, S. P. (1995). J. Biol. Chem. 270, 29,433–29,438.

    CAS  Google Scholar 

  32. Fang, Y., Fliss, A. E., Robins, D. M., and Caplan, A. J. (1996). J. Biol. Chem. 271, 28,697–28,702.

    CAS  Google Scholar 

  33. Freeman, B. C., Felts, S. J., Toft, D. O., and Yamamoto, K. R. (2000). Genes Dev. 14, 422–434.

    PubMed  CAS  Google Scholar 

  34. Scherrer, L. C., Dalman, F. C., Massa, E., Meshinchi, S., and Pratt, W. B. (1990). J. Biol. Chem. 265, 21,397–21,400.

    CAS  Google Scholar 

  35. Dittmar, K. D., Hutchison, K. A., Owens-Grillo, J. K., and Pratt, W. B. (1996). J. Biol. Chem. 271, 12,833–12,839.

    CAS  Google Scholar 

  36. Dittmar, K. D., Demady, D. R., Stancato, L. F., Krishna, P., and Pratt, W. B. (1997). J. Biol. Chem. 272, 21,213–21,220.

    CAS  Google Scholar 

  37. Knoblauch, R. and Garabedian, M. J. (1999). Mol. Cell. Biol. 19, 3748–3759.

    PubMed  CAS  Google Scholar 

  38. Froesch, B. A., Takayama, S., and Reed, J. C. (1998). J. Biol. Chem. 273, 11,660–11,666.

    Article  CAS  Google Scholar 

  39. Baughman, G., Wiederrecht, G. J., Chang, F., Martin, M. M., and Bourgeois, S. (1997). Biochem. Biophys. Res. Commun. 232, 437–443.

    Article  PubMed  CAS  Google Scholar 

  40. Veldscholte, J., Berrevoets, C. A., Brinkman, A. O., Grootegoed, J. A., and Mulder, E. (1992). Biochemistry 31, 2393–2399.

    Article  PubMed  CAS  Google Scholar 

  41. Devin-Leclerc, J., Meng, X., Delahaya, F., Leclerc, P., Bauilieu, E.-E., and Catelli, M.-G. (1998). Mol. Endocrinol. 12, 842–854.

    Article  PubMed  CAS  Google Scholar 

  42. Hayes, S. A. and Dice, J. F. (1996). J. Cell Biol. 132, 255–258.

    Article  PubMed  CAS  Google Scholar 

  43. Wagner, I., Arlt, H., van Dyck, L., Langer, T., and Neupert, W. (1994). EMBO J. 13, 5135–5145.

    PubMed  CAS  Google Scholar 

  44. Bercovich, B., Stancovski, I., Mayer, A., Blumenfeld, N., Laszlo, A., Schwartz, A. L., and Ciechanover, A. (1997). J. Biol. Chem. 272, 9002–9010.

    Article  PubMed  CAS  Google Scholar 

  45. Schwartz, A. L. and Ciechanover, A. (1999). Annu. Rev. Med. 50, 57–74.

    Article  PubMed  CAS  Google Scholar 

  46. Whitesell, L., Sutphin, P. D., Pulcini, E. J., Martinez, J. D., and Cook, P. H. (1998). Mol. Cell. Biol. 18, 1517–1524.

    PubMed  CAS  Google Scholar 

  47. Grenert, J. P., Sullivan, W. P., Fadden, P., Haystead, T. A. J., Clark, J., Mimnaugh, E., Krutzsch, H., Ochel, H. J., Schulte, T. W., Sausville, E., Neckers, L. M., and Toft, D. O. (1997). J. Biol. Chem. 272, 23,843–23,850.

    Article  CAS  Google Scholar 

  48. Smith, D. F., Whitesell, L., Nair, S. C., Chen, S., Prapapanich, V., and Rimerman, R. A. (1995). Mol. Cell. Biol. 15, 6804–6812.

    PubMed  CAS  Google Scholar 

  49. Segnitz, B. and Gehring, U. (1997). J. Biol. Chem. 272, 18,694–18,701.

    Article  CAS  Google Scholar 

  50. Whitesell, L. and Cook, P. (1996). Mol. Endocrinol. 10, 705–712.

    Article  PubMed  CAS  Google Scholar 

  51. Dauvois, S., White, R., and Parker, M. G. (1993). J. Cell Sci. 106, 1377–1388.

    PubMed  CAS  Google Scholar 

  52. Luders, J., Demand, J., and Hohfeld, J. (2000). J. Biol. Chem. 275, 4613–4617.

    Article  PubMed  CAS  Google Scholar 

  53. vom Baur, E., Zechel, C., Heery, D., Heine, M. J. S., Garnier, J. M., Vivat, V., Le Douarin, B., Gronemeyer, H., Chambon, P., and Losson, R. (1996). EMBO J. 15, 110–124.

    PubMed  CAS  Google Scholar 

  54. Zhang, J., Guenther, M. G., Carthew, R. W., and Lazar, M. A. (1998). Genes Dev. 12, 1775–1780.

    PubMed  CAS  Google Scholar 

  55. Lee, J. W., Ryan, F., Swaffield, J. C., Johnson, S. A., and Moore, D. D. (1995). Nature 374, 91–94.

    Article  PubMed  CAS  Google Scholar 

  56. Akner, G., Wikstrom, A.-C., and Gustafsson, J.-A. (1995). J. Steroid Biochem. Mol. Biol. 52, 1–16.

    Article  PubMed  CAS  Google Scholar 

  57. Akner, G., Sundquist, K. G., Denis, M., Wikstrom, A. C., and Gustafsson, J.-A. (1990). Eur. J. Cell Biol. 53, 390–401.

    PubMed  CAS  Google Scholar 

  58. Lombes, M., Binart, N., Delahaye, F., Baulieu, E. E., and Rafestin-Oblin, M. E. (1994). Biochem. J. 302, 191–197.

    PubMed  CAS  Google Scholar 

  59. van der Kwast, T. H., Schalken, J., Ruizeveld de Winter, J. A., van Vronnhoven, C. C. J., Mulder, E., Boersma, W., and Trapman, J. (1991). Int. J. Cancer 48, 189–193.

    Article  PubMed  Google Scholar 

  60. Takeda, H., Chodak, G., Mutchnik, S., Nakamoto, T., and Chang, C. (1989). J. Endocrinol. 126, 17–25.

    Article  Google Scholar 

  61. Husmann, D. A., Wilson, C. M., McPhaul, M. J., Tilley, W. D., and Wilson, J. D. (1990). Endocrinology 126, 2359–2368.

    Article  PubMed  CAS  Google Scholar 

  62. Jenster, G., Trapman, J., and Brinkmann, A. O. (1993). Biochemical J. 293, 761–768.

    CAS  Google Scholar 

  63. Guiochon-Mantel, A., Lescop, P., Christin-Maitre, S., Loosfelt, H., Perrot-Applanat, M., and Milgrom, E. (1991). EMBO J. 10, 3851–3859.

    PubMed  CAS  Google Scholar 

  64. Welshons, W. V., Lieberman, M. E., and Gorski, J. (1984). Nature 307, 747–749.

    Article  PubMed  CAS  Google Scholar 

  65. Perrot-Applanat, M., Groyer-Picard, M., Logeat, F., and Milgrom, E. (1986). J. Cell Biol. 102, 1191–1199.

    Article  PubMed  CAS  Google Scholar 

  66. King, W. J. and Greene, G. L. (1984). Nature 307, 745–747.

    Article  PubMed  CAS  Google Scholar 

  67. Ylikomi, T., Bocquel, M. T., Berry, M., Gronemeyer, H., and Chambon, P. (1992). EMBO J. 11, 3681–3694.

    PubMed  CAS  Google Scholar 

  68. Savory, J. G., Hsu, B., Laquian, I. R., Giffin, W., Reich, T., Hache, R. J., and Lefebvre, Y. A. (1999). Mol. Cell. Biol. 19, 1025–1037.

    PubMed  CAS  Google Scholar 

  69. Liu, J. and DeFranco, D. B. (1999). Mol. Endocrinol. 13, 355–365.

    Article  PubMed  CAS  Google Scholar 

  70. Kang, K. I., Devin, J., Cadepond, F., Jibard, N., Guiochon-Mantel, A., Baulieu, E.-E., and Catelli, M.-G. (1994). Proc. Natl. Acad. Sci. USA 91, 340–344.

    Article  PubMed  CAS  Google Scholar 

  71. Mandell, R. B. and Feldherr, C. M. (1990). J. Cell Biol. 111, 1775–1783.

    Article  PubMed  CAS  Google Scholar 

  72. Henriksson, M., Classon, M., Axelson, H., Klein, G., and Thyberg, J. (1992). Exp. Cell Res. 203, 383–394.

    Article  PubMed  CAS  Google Scholar 

  73. Yang, J. and DeFranco, D. B. (1994). mol. Cell. Biol. 14, 5088–5098.

    PubMed  CAS  Google Scholar 

  74. Czar, M. J., Lyons, R. H., Welsh, M. J., Renoir, J.-M., and Pratt, W. B. (1995). Mol. Endocrinol. 9, 1549–1560.

    Article  PubMed  CAS  Google Scholar 

  75. Czar, M. J., Owens-Grillo, J. K., Yem, A. W., Leach, K. L., Deibel, M. R., Welsh, M. J., and Pratt, W. B. (1994). Mol. Endocrinol. 8, 1731–1741.

    Article  PubMed  CAS  Google Scholar 

  76. Pratt, W. B., Czar, M. J., Stancato, L. F., and Owens, J. K. (1993). J. Steroid Biochem. Mol. Biol. 46, 269–279.

    Article  PubMed  CAS  Google Scholar 

  77. Renoir, J. M., Radanyi, C., Faber, L. E., and Baulieu, E. E. (1990). J. Biol. Chem. 265, 10,740–10,745.

    CAS  Google Scholar 

  78. Kamimura, S., Gallieni, M., Zhong, M., Beron, W., Slatopolsky, E., and Dusso, A. (1995). J. Biol. Chem. 270, 22,160–22,166.

    CAS  Google Scholar 

  79. Barsony, J., Pike, J. W., DeLuca, H. F., and Marx, S. J. (1990). J. Cell Biol. 111, 2385.

    Article  PubMed  CAS  Google Scholar 

  80. Galigniana, M. D., Housley, P. R., DeFranco, D. B., and Pratt, W. B. (1999). J. Biol. Chem. 274, 16222–16227.

    Article  PubMed  CAS  Google Scholar 

  81. Czar, M. J., Galigniana, M. D., Silverstein, A. M., and Pratt, W. B. (1997). Biochemistry 36, 7776–7785.

    Article  PubMed  CAS  Google Scholar 

  82. Galigniana, M. D., Scruggs, J. L., Herrington, J., Welsh, M. J., Carter-Su, C., Housley, P. R., and Pratt, W. B. (1998). Mol. Endocrinol. 12, 1903–1913.

    Article  PubMed  CAS  Google Scholar 

  83. Gorlich, D. and Kutay, U. (1999). Annu. Rev. Cell Dev. Biol. 15, 607–660.

    Article  PubMed  CAS  Google Scholar 

  84. Kaffman, A. and O’Shea, E. K. (1999). Annu. Rev. Cell Dev. Biol. 15, 291–339.

    Article  PubMed  CAS  Google Scholar 

  85. Henry, K. W., Yuan, X., Koszewski, N. J., Onda, H., Kwiatkowski, D. J., and Noonan, D. J. (1998). J. Biol. Chem. 273, 20,535–20,539.

    Article  CAS  Google Scholar 

  86. Nellist, M., van Slegtenhorst, M. A., Goedbloed, M., van den Ouweland, A. M. W., Halley, D. J. J., and van der Sluijs, P. (1999). J. Biol. Chem. 274, 35,647–35,652.

    Article  CAS  Google Scholar 

  87. Hsiao, P. W., Lin, D., Nakao, R., and Chang, C. (1999). J. Biol. Chem. 274, 20229–20234.

    Article  PubMed  CAS  Google Scholar 

  88. Kahana, J. A. and Cleveland, D. W. (1999). J. Cell Biol. 146, 1205–1209.

    Article  PubMed  CAS  Google Scholar 

  89. Chen, Y., Chen, P.-L., Chen, C.-F., Sharp, Z. D., and Lee, W.-H. (1999). Proc. Natl. Acad. Sci. USA 96, 4443–4448.

    Article  PubMed  CAS  Google Scholar 

  90. Neckers, L., Schulte, T. W., and Mimnaugh, E. (2000). Invest. New Drugs 17, 361–373.

    Article  Google Scholar 

  91. Supko, J. G., Hickman, R. L., Grever, M. R., and Malspeis, L. (1995). Cancer Chemother. Pharmacol. 36, 305–315.

    PubMed  CAS  Google Scholar 

  92. Paulson, H. L. and Fischbeck, K. H. (1996). Ann. Rev. Neurosci. 19, 79–107.

    Article  PubMed  CAS  Google Scholar 

  93. Stenoien, D. L., Cummings, C. J., Adams, H. P., Mancini, M. G., Patel, K., DeMartino, G. N., Marcell, M., Weigel, N. L., and Mancini, M. A. (1999). Hum. Mol. Genet. 8, 731–741.

    Article  PubMed  CAS  Google Scholar 

  94. Kobayashi, Y., Kume, A., Li, M., Doyu, M., Hata, M., Ohtsuka, K., and Sobue, G. (2000). J. Biol. Chem. 275, 8772–8778.

    Article  PubMed  CAS  Google Scholar 

  95. Cummings, C. J., Mancini, M. A., Antalffy, B., DeFranco, D. B., Orr, H. T., and Zoghbi, H. (1998). Nature Genet. 19,0 148–154.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Chawnshang Chang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Heinlein, C.A., Chang, C. Role of chaperones in nuclear translocation and transactivation of steroid receptors. Endocr 14, 143–149 (2001). https://doi.org/10.1385/ENDO:14:2:143

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1385/ENDO:14:2:143

Key Words

Navigation