Nature Publishing Group, publisher of Nature, and other science journals and reference works
Nature
my account e-alerts subscribe register
   
Sunday 25 June 2017
Journal Home
Current Issue
AOP
Archive
Download PDF
References
Export citation
Export references
Send to a friend
More articles like this

Letters to Nature
Nature 348, 166 - 168 (08 November 1990); doi:10.1038/348166a0

Reduced levels of hsp90 compromise steroid receptor action in vivo

Didier Picard*, Bushra Khursheed, Michael J. Garabedian*, Marc G. Fortin, Susan Lindquist & Keith R. Yamamoto*

*Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, California 94143-0448, USA
Howard Hughes Medical Institute, Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, Illinois 60637, USA
Present addresses: Département de Biologie Cellulaire, Université de Genève, Sciences III, 30, Quai Ernest-Ansermet, 1211 Genève 4, Switzerland (D.P.); and Department of Crop Sciences, University of California, Davis, Davis, California 95616, USA (M.G.F.).

SIGNALLING by steroid hormones is mediated by receptor proteins that bind hormonal ligands and regulate the transcription of specific genes. The heat-shock protein hsp90 seems to associate selectively with unliganded receptors (aporeceptors), but it has not been determined whether this interaction affects receptor function in vivo. To address the role of hsp90, we have taken advantage of the capacity of mammalian steroid receptors to function in yeast1–4. We constructed a strain of Saccharomyces cerevisiae in which hsp90 expression was regulatable and could be reduced more than 20-fold relative to wild type. At low levels of hsp90, aporeceptors seem to be mostly hsp90-free, yet fail to enhance transcription; on hormone addition, the receptors are activated but with markedly reduced efficiency. Thus hsp90 does not inhibit receptor function solely by steric interference; rather, hsp90 seems to facilitate the subsequent response of the aporeceptor to the hormonal signal. This is the first biological evidence that hsp90 acts in the signal transduction pathway for steroid receptors.

------------------

References

1. Schena, M. & Yamamoto, K. R. Science 241, 965−967 (1988). | PubMed | ISI | ChemPort |
2. Metzger, D., White, J. H. & Chambon, P. Nature 334, 31−36 (1988). | Article | PubMed | ISI | ChemPort |
3. McDonnell, D. P., Pike, J. W., Drutz, D. J., Butt, T. R. & O'Malley, B. W. Molec. Cell. Biol. 9, 3517−3523 (1989). | PubMed | ChemPort |
4. Picard, D., Schena, M. & Yamamoto, K. R. Gene 86, 257−261 (1990). | Article | PubMed | ISI | ChemPort |
5. Borkovich, K. A., Farrelly, F. W., Finkelstein, D. B., Taulien, J. & Lindquist, S. Molec. cell. Biol. 9, 3919−3930 (1989). | PubMed | ChemPort |
6. Lindquist, S. & Craig, E. A. A. Rev. Genet. 22, 631−677 (1988). | Article | ISI | ChemPort |
7. Groyer, A., Schweizer-Groyer, G., Cadepond, F., Mariller, M. & Baulieu, E.-E. Nature 328, 624−626 (1987). | Article | PubMed | ChemPort |
8. Sanchez, E. R. et al. J. biol. Chem. 262, 6986−6991 (1987). | PubMed | ChemPort |
9. Willmann, T. & Beato, M. Nature 324, 688−691 (1986). | Article | PubMed | ISI | ChemPort |
10. Klein-Hitpass, L. et al. Cell 60, 247−257 (1990). | PubMed | ChemPort |
11. Bresnick, E. H., Dalman, F. C., Sanchez, E. R. & Pratt, W. B. J. biol. Chem. 264, 4992−4997 (1989). | PubMed | ISI | ChemPort |
12. Picard, D., Salser, S. J. & Yamamoto, K. R. Cell 54, 1073−1080 (1988). | Article | PubMed | ISI | ChemPort |
13. Picard, D., Kumar, V., Chambon, P. & Yamamoto, K. R. Cell Reg. 1, 291−299 (1990). | ChemPort |
14. Eilers, M., Picard, D., Yamamoto, K. R. & Bishop, J. M. Nature 340, 66−68 (1989). | Article | PubMed | ISI | ChemPort |
15. Pratt, W. B. et al. J. biol. Chem. 263, 267−273 (1988). | PubMed | ChemPort |
16. Dalman, F. C. et al. J. biol. Chem. 264, 19815−19821 (1989). | PubMed | ChemPort |
17. Howard, K. J., Holley, S. J., Yamamoto, K. R. & Distelhorst, C. W. J. biol. Chem., 265, 11928−11930 (1990). | PubMed | ISI | ChemPort |
18. Godowski, P. J., Rusconi, S., Miesfeld, R. & Yamamoto, K. R. Nature 325, 365−368 (1987). | Article | PubMed | ISI | ChemPort |
19. Yamamoto, K. R., Godowski, P. J. & Picard, D. Cold Spring Harbor Symp. quant Biol. 53, 803−811 (1988). | PubMed | ChemPort |
20. Johnston, M. & Davis, R. W. Molec. cell. Biol. 4, 1440−1448 (1984). | PubMed | ISI | ChemPort |
21. Sikorski, R. S. & Hieter, P. Genetics 122, 19−27 (1989). | PubMed | ISI | ChemPort |
22. Schena, M., Freedman, L. P. & Yamamoto, K. R. Genes Dev. 3, 1590−1601 (1989). | PubMed | ISI | ChemPort |
23. Patel, P. D., Sherman, T. G., Goldman, D. J. & Watson, S. J. Molec. Endocr. 3, 1877−1885 (1989). | PubMed | ChemPort |
24. Green, S. et al. Nature 320, 134−139 (1986). | Article | PubMed | ISI | ChemPort |
25. Tora, L. et al. EMBO J. 8, 1981−1986 (1989). | PubMed | ISI | ChemPort |
26. Klein-Hitpass, L., Schorpp, M., Wagner, U. & Ryffel, G. U. Cell 46, 1053−1061 (1986). | Article | PubMed | ChemPort |
27. Gametchu, B. & Harrison, R. W. Endocrinology 114, 274−279 (1984). | PubMed | ISI | ChemPort |
28. Okret, S., Wikström, A.-C., Wrange, Ö., Andersson, B. & Gustafsson, J.-Å. Proc. natn. Acad. Sci. U.S.A. 81, 1609−1613 (1984). | ChemPort |
29. Simons, S. S. Jr, Thompson, E. B. & Johnson, D. F. Biochem. biophys. Res. Commun. 86, 793−800 (1979). | Article | ChemPort |
30. Yocum, R. R., Hanley, S., West, R. W. Jr & Ptashne, M. Molec. cell. Biol. 4, 1985−1998 (1984). | PubMed | ISI | ChemPort |



© 1990 Nature Publishing Group
Privacy Policy