Comprehensive Physiology Wiley Online Library

Steroid Hormone Receptor Families

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 Molecular Composition of Receptor Proteins: Primary Structural Homologies and Functional Domains
1.1 The A/B Region of Steroid Receptors Contains a Hormone‐Independent Activation Function
1.2 The C Region Encodes a Specific DNA‐Binding Function
1.3 The D Region (the Hinge Domain) Contains a Nuclear Localization Signal
2 The E/F Region Contains the Hormone‐Binding Domain, a Dimerization Motif, Steroid Receptor Repressor Activity, and a Receptor Agonist‐Dependent Transcriptional Activation Function
3 Receptor‐Associated Proteins and the Oligomeric Structure of Steroid Receptors
3.1 Major Heat Shock Proteins
4 Cross‐Talk with Other Signal‐Transduction Pathways
4.1 Cyclic Adenosine Monophosphate and Activation of Steroid Receptors
4.2 Transcriptional Interference
4.3 Pathways That Converge on the Estrogen Receptor
5 Role of Phosphorylation in Steroid Receptor Structure and Function
5.1 Sites of Phosphorylation, Functional Significance, and Regulatory Kinases
5.2 Estrogen Receptor Phosphorylation
5.3 Progesterone Receptor Phosphorylation
5.4 Glucocorticoid Receptor Phosphorylation
5.5 Vitamin D Receptor Phosphorylation
6 Transactivation by Steroid Receptors
7 Antihormones and Their Modes of Action
7.1 RU486, an Agonist/Antagonist of Progesterone Receptor
7.2 ZK98299, a Full Antagonist of Progesterone Receptor
7.3 Antiestrogens and Estrogen Receptor Function
8 Steroid Receptors and Clinical Management of Cancer
8.1 Cancer: Molecular Aspects
8.2 Breast Cancer, Tumor Suppressors, and Estrogen
8.3 Paradoxical Effects of Estrogen: Molecular Aspects
9 Future Directions
Figure 1. Figure 1.

Primary domain structure of human estrogen receptor. Illustrated are regions A–F with subdomins and their functions represented as block lines. Also shown are the kinases that phosphorylate human estrogen receptor and their sites of action. MAPK, mitogen‐activated protein kinase; CKII, casein kinase II; Src, tyrosine‐specific kinase protooncogene originally isolated as the Rous sarcoma (Src) virus oncogene; HSP, heat shock protein; AF, activation function.

Figure 2. Figure 2.

Linkage of estrogen and antiestrogen action to the tumor suppressors, retinoblastoma protein (pRB), and p53. 1, Increase in the levels/activity of p53 induced by 17β‐estradiol (E2); 2, wild‐type p53 induction of cell‐cycle inhibitors and apoptosis; 3, antiestrogen ICI 182,780 causes down‐regulation of cyclin D1, a decrease in the activity of cyclin D1‐associated Cdk2 activity, and dephosphorylation of pRB; 4, dephosphorylated pRB represses E2F, a transcription factor that induces G1 to S phase transition. Cells arrested at G1 phase of the cell cycle. Cdk, cylin‐dependent kinase; p53, protein product of the p53 gene.

Figure 3. Figure 3.

Effect of charcoal treatment on p53 levels in T47D cells: Western analysis. T47D cells were plated in whole serum for 2 days. Cells were then cultured for various times in medium containing whole (C) or charcoal‐treated serum (3–8 days). All cells were harvested at the same time after 10 days of culturing. Cells were extracted and analyzed for protein, and a total of 100 μg of protein/lane was applied for SDS‐PAGE and Western blot analyses as described 125. [Taken with permission from the American Society for Biochemistry and Molecular Biology for the article J. Biol. Chem. 270: 28507–28510, 1995.]

Figure 4. Figure 4.

Effect of estradiol concentrations on p53 levels in T47D cells cultured in charcoal‐treated serum: Western blot analysis. T47D cells were plated for 2 days in medium containing whole serum and then for another 6 days in charcoal‐treated serum plus estradiol as indicated. Lane C represents cells cultured in whole serum for the entire time with no exogenous estradiol treatment. Lane 0 represents a sample with charcoal treatment but no estradiol addition (control). All cells were harvested at the same time after 8 days of culturing. Procedures for SDS‐PAGE and Western blot analyses were the same as those used for the experiment described in Figure 3 and detailed in reference 125. [Taken with permission from the American Society for Biochemistry and Molecular Biology for the article J. Biol. Chem. 270: 28507–28510, 1995.]



Figure 1.

Primary domain structure of human estrogen receptor. Illustrated are regions A–F with subdomins and their functions represented as block lines. Also shown are the kinases that phosphorylate human estrogen receptor and their sites of action. MAPK, mitogen‐activated protein kinase; CKII, casein kinase II; Src, tyrosine‐specific kinase protooncogene originally isolated as the Rous sarcoma (Src) virus oncogene; HSP, heat shock protein; AF, activation function.



Figure 2.

Linkage of estrogen and antiestrogen action to the tumor suppressors, retinoblastoma protein (pRB), and p53. 1, Increase in the levels/activity of p53 induced by 17β‐estradiol (E2); 2, wild‐type p53 induction of cell‐cycle inhibitors and apoptosis; 3, antiestrogen ICI 182,780 causes down‐regulation of cyclin D1, a decrease in the activity of cyclin D1‐associated Cdk2 activity, and dephosphorylation of pRB; 4, dephosphorylated pRB represses E2F, a transcription factor that induces G1 to S phase transition. Cells arrested at G1 phase of the cell cycle. Cdk, cylin‐dependent kinase; p53, protein product of the p53 gene.



Figure 3.

Effect of charcoal treatment on p53 levels in T47D cells: Western analysis. T47D cells were plated in whole serum for 2 days. Cells were then cultured for various times in medium containing whole (C) or charcoal‐treated serum (3–8 days). All cells were harvested at the same time after 10 days of culturing. Cells were extracted and analyzed for protein, and a total of 100 μg of protein/lane was applied for SDS‐PAGE and Western blot analyses as described 125. [Taken with permission from the American Society for Biochemistry and Molecular Biology for the article J. Biol. Chem. 270: 28507–28510, 1995.]



Figure 4.

Effect of estradiol concentrations on p53 levels in T47D cells cultured in charcoal‐treated serum: Western blot analysis. T47D cells were plated for 2 days in medium containing whole serum and then for another 6 days in charcoal‐treated serum plus estradiol as indicated. Lane C represents cells cultured in whole serum for the entire time with no exogenous estradiol treatment. Lane 0 represents a sample with charcoal treatment but no estradiol addition (control). All cells were harvested at the same time after 8 days of culturing. Procedures for SDS‐PAGE and Western blot analyses were the same as those used for the experiment described in Figure 3 and detailed in reference 125. [Taken with permission from the American Society for Biochemistry and Molecular Biology for the article J. Biol. Chem. 270: 28507–28510, 1995.]

References
 1. Ali, S., D. Metzger, J. M. Bornert, and P. Chambon. Modulation of transcriptional activation by ligand‐dependent phosphorylation of the human oestrogen receptor A/B region. EMBO J. 12: 1153–1160, 1993.
 2. Amero, S.A., R. H. Kretsinger, N. D. Moncrief, K. R. Yamamoto, and W. R. Pearson. The origin of nuclear receptor proteins: a single precursor distinct from other transcription factors. Mol. Endocrinol. 6: 3–7, 1992.
 3. Arnold, S. F., and A. C. Notides. An antiestrogen: a phosphotyrosyl peptide that blocks dimerization of the human estrogen receptor. Proc. Natl. Acad. Sci., U.S.A. 92: 7475–7479, 1995.
 4. Arnold, S. F., J. D. Obourn, H. Jaffe, and A. C. Notides. Serine 167 is the major estradiol‐induced phosphorylation site on the human estrogen receptor. Mol. Endocrinol. 8: 1208–1214, 1994.
 5. Arnold, S. F., J. D. Obourn, H. Jaffe, and A. C. Notides. Phosphorylation of the human estrogen receptor by mitogen‐activated protein kinase and casein kinase II: consequence on DNA binding. J. Steroid Biochem. Mol. Biol. 55: 163–172, 1995.
 6. Arnold, S. F., J. D. Obourn, H. Jaffe, and A. C. Notides. Phosphorylation of the human estrogen receptor on tyrosine 537 in vivo and by src family tyrosine kinases in vitro. Mol. Endocrinol. 9: 24–33, 1995.
 7. Arnold, S. F., D. P. Vorojeikina, and A. C. Notides. Phosphorylation of tyrosine 537 on the human estrogen receptor is required for binding to an estrogen response element. J. Biol. Chem. 270: 30205–30212, 1995.
 8. Aronica, S. M., W. L. Kraus, and B. S. Katzenellenbogen. Estrogen action via the cAMP signalling pathway: stimulation of adenylate cyclase and cAMP‐regulated gene transcription. Proc. Natl. Acad. Sci., U.S.A. 91: 8517–8521, 1994
 9. Atrache, V., T. Ratajczak, S. Senafi, and R. Hahnel. Purification of the molybdate‐stabilized 9–1OS estradiol receptor from calf uterus. J. Biol. Chem. 260: 5936–5941, 1985.
 10. Auricchio, F., A. Migliaccio, M. Di Domenico, and E. Nola. Oestradiol stimulates tyrosine phosphorylation and hormone binding activity of its own receptor in a cell‐free system. EMBO J. 6: 2923–2929, 1987.
 11. Bagchi, M. K., J. F. Elliston, S. Y. Tsai, D. P. Edwards, M. J. Tsai, and B. W. O'Malley. Steroid hormone‐dependent interaction of human progesterone receptor with its target enhancer element. Mol. Endocrinol. 2: 1221–1229, 1988.
 12. Bagchi, M. K., S. Y. Tsai, M. J. Tsai, and B. W. O'Malley. Identification of a functional intermediate in receptor activation in progesterone‐dependent cell‐free transcription. Nature 345: 547–550, 1990.
 13. Bagchi, M. K., S. Y. Tsai, M. J. Tsai, and B. W. O'Malley. Ligand and DNA‐dependent phosphorylation of human progesterone receptor in vitro. Proc. Natl. Acad. Sci. U.S.A. 89: 2664–2668, 1992.
 14. Bai, W., S. Tullos, and N. L. Weigel. Phosphorylation of ser530 facilitates hormone‐dependent transcriptional activation of the chicken progesterone receptor. Mol. Endocrinol. 8: 1465–1473, 1994.
 15. Bailly, A., C. Le Page, M. Rauch, and E. Milgrom. Sequence‐specific DNA binding of the progesterone receptor to the uteroglobin gene: effects of hormone, antihormone and receptor phosphorylation. EMBO J. 5: 3235–3241, 1986.
 16. Bartek, J., R. Iggo, J. Gannon, and D. P. Lane. Genetic and immunochemical analysis of mutant p53 in human breast cancer cell lines. Oncogene 5: 893–899, 1990.
 17. Baulieu, E. E. Contragestion and other clinical applications of RU486, an antiprogesterone at the receptor. Science 245: 1351–1357, 1989.
 18. Beato, M. Gene regulation by steroid hormones. Cell 56: 335–344, 1989.
 19. Beato, M., V. Sica, F. Bresciani, and A. Weisz. 17‐beta estradiol induces cyclin D1 gene transcriptin, p36(D1)‐p34(CDK4) complex activation and p105(RB) phosphorylation during mitogenic stimulation of G arrested human breast cancer cells. Oncogene 12: 2315–2324, 1996.
 20. Beck, C. A., N. L. Weigel, and D. P. Edwards. Effects of hormone and cellular modulators of protein phosphorylation on transcriptional activity, DNA binding, and phosphorylation of human progesterone receptors. Mol. Endocrinol. 6: 607–620, 1992.
 21. Beck, C. A., N. L. Weigel, M. L. Moyer, S. K. Nordeen, and D. P. Edwards. The progesterone receptor antagonist RU486 acquires agonist activity upon stimulation of cAMP signaling pathways. Proc. Natl. Acad. Sci., U.S.A. 90: 4441–4445, 1993.
 22. Beckmann, R. P., L. E. Mizzen, and W. J. Welch. Interaction of hsp 70 with newly synthesized proteins: implications for protein folding and assembly. Science 248: 850–854, 1990.
 23. Ben‐Levy, R., H. F. Paterson, C. J. Marshall, and Y. Yarden. A single phosphorylation site confers oncogenicity to the Neu/ ErbB‐2 receptor and enables coupling to the MAP kinase pathway. EMBO J. 13: 3302–3311, 1994.
 24. Berg, J. M. Potential metal‐binding domains in nucleic acid binding proteins. Science 232: 485–487, 1986.
 25. Berg, J. M. DNA binding specificity of steroid receptors. Cell 57: 1065–1068, 1989.
 26. Berry, M., D. Metzger, and P. Chambon. Role of the two activating domains of the oestrogen receptor in the cell‐type and promoter‐context dependent agonistic activity of the antioestrogen 4–hydroxytamoxifen. EMBO J. 9: 2811–2818, 1990.
 27. Binart, N., B. Chambraud, B. Dumas, D. A. Rowlands, C. Bigogne, J. M. Levin, J. Garnier, E. E. Baulieu, and M. G. Catelli. The cDNA‐derived amino acid sequence of chick heat shock protein Mr 90,000 (hsp‐90) reveals a “DNA like” structure: potential site of interaction with steroid receptors. Biochem. Biophys. Res. Commun. 159: 140–147, 1989.
 28. Bocquel, M. T., V. Kumar, C. Strieker, P. Chambon, and H. Gronemeyer. The contribution of the n‐ and c‐terminal regions of steroid receptors to activation of transcription is both receptor and cell specific. Nucleic Acids Res. 17: 2581–2595, 1989.
 29. Bodwell, J. E., E. Orti, J. M. Coull, D. C. J. Pappin, L. I. Smith, and F. Swift. Identification of phosphorylated sites in the mouse glucocorticoid receptor. J. Biol. Chem. 266: 7549–7555, 1991.
 30. Bourgeois, S., M. Pfahl, and E. E. Baulieu. DNA binding properties of glucocorticosteroid receptors bound to the steroid antagonist RU‐486. EMBO J. 3: 751–755, 1984.
 31. Cadepond, F., G. Schweizer‐Groyer, I. Segard‐Maurel, N. Jibard, S. M. Hollenberg, V. Giguire, R. M. Evans, and E. E. Baulieu. Heat shock protein 90 as a critical factor in maintaining glucocorticosteroid receptor in a nonfunctional state. J. Biol. Chem. 266: 5834–5841, 1991.
 32. Carlstedt‐Duke, J., P. E. Stromstedt, B. Persson, E. Cederlund, J. A. Gustafsson, and H. Jornvall. Identification of hormone‐interacting amino acid residues within the steroid‐binding domain of the glucocorticoid receptor in relation to other steroid hormone receptors. J. Biol. Chem. 263: 6842–6846, 1988.
 33. Carlstedt‐Duke, J., P. E. Stromstedt, O. Wrange, T. Bergman, J. A. Gustafsson, and H. Jornvall. Domain structure of the glucocorticoid receptor protein. Proc. Natl. Acad. Sci., U.S.A. 84: 4437–4440, 1987.
 34. Carson, M. A., M. J. Tsai, O. M. Conneely, B. L. Maxwell, J. H. Clark, A. D. W. Dobson, A. Elbrecht, D. O. Toft, W. T. Schrader, and B.W. O'Malley. Structure–function properties of the chicken progesterone receptor A synthesized from complimentary deoxyribonucleic acid. Mol. Endocrinol. 1: 791–801, 1987.
 35. Carson‐Jurica, M. A., A. T. Lee, A. W. Dobson, O. M. Conneely, W. T. Schrader, and B. W. O'Malley. Interaction of the chicken progesterone receptor with heat shock protein (hsp) 90. J. Steroid Biochem. 34: 1–9, 1989.
 36. Casey, G., M. Lo‐Hsueh, M. E. Lopez, B. Vogelstein, and E. J. Stanbridge. Growth suppression of human breast cancer cells by the introduction of a wild‐type p53 gene. Oncogene 6: 1791–1797, 1991.
 37. Castoria, G., A. Migliaccio, S. Green, M. Di Domenico, P. Chambon, and F. Auricchio. Properties of a purified estradiol‐dependent calf uterus tyrosine kinase. Biochemistry 32: 1740–1750, 1993.
 38. Cavailles, V., S. Dauvois, P. S. Danielian, and M. G. Parker. Interaction of proteins with transcriptionally active estrogen receptors. Proc. Natl. Acad. Sci., U.S.A. 91: 10009–10013, 1994.
 39. Cavailles, V., S. Dauvois, F. L'Horset, G. Lopez, S. Hoare, J. Kushner, and M. G. Parker. Nuclear factor RIP140 modulates transcriptional activation by the estrogen receptor. EMBO J. 14: 3741–3751, 1995.
 40. Chambraud, B., M. Berry, G. Redeuilh, P. Chambon, and E. E. Baulieu. Several regions of the human estrogen receptor are involved in the formation of receptor‐heat shock protein 90 complexes. J. Biol. Chem. 265: 20686–20691, 1990.
 41. Chang, C., J. Kokontis, and S. Liao. Molecular cloning of human and rat complimentary DNA encoding androgen receptors. Science 240: 324–326, 1998.
 42. Chasserot‐Golaz, S., and G. Beck. An approach to the mechanism of the potent antiglucocorticoid: 17β‐hydroxy‐11β‐4‐dimethylaminophenyl‐17a‐propynyl‐estra‐4,9‐dien‐3‐one. J. Steroid Biochem. 21: 585–591, 1984.
 43. Chen, Y., C. F. Chen, D. J. Riley, D. C. Allred, P. L. Chen, D. Von Hoff, C. K. Osborne, and W. H. Lee. Aberrant subcellular localization of BRCA1 in breast cancer. Science 270: 789–791, 1995.
 44. Chiba, H., M. Muramatsu, A. Nomoto, and H. Kato. Two human homologues of Saccharomyces cerevisiae SW12/SNF2 and Drosophila brahma are transcriptional coactivators cooperating with the estrogen receptor and the retinoic acid receptor. Nucleic Acids Res. 22: 1815–1820, 1994.
 45. Choy, B., and M. R. Green. Eukaryotic activators function during multiple steps of preinitiation complex assembly. Nature 366: 531–536, 1993.
 46. Conneely, O. M., A. D. W. Dobson, M. J. Tsai, W. G. Beattie, D. O. Toft, C. S. Huckaby, T. Zarucki, W. T. Schrader, and B. W. O'Malley. Sequence and expression of a functional chicken progesterone receptor. Mol. Endocrinol. 1: 517–525, 1987.
 47. Conneely, O. M., W. P. Sullivan, D. O. Toft, M. Birnbaumer, R. G. Cook, B. L. Maxwell, T. Zarucki‐Schultz, G. L. Green, W. T. Schrader, and B. W. O'Malley. Molecular cloning of the chicken progesterone receptor. Science 233: 767–770, 1986.
 48. Csermely, P., and R. C. Kahn. The 90–kDa heat shock protein (hsp‐90) possesses an ATP binding site and autophosphorylating activity. J. Biol. Chem. 266: 4943–4950, 1991.
 49. Dahlman‐Wright, K., A. Wright, J. A. Gustafsson, and J. Carstedt‐Duke. Interaction of the glucocorticoid receptor DNA‐binding domain with DNA as a dimer is mediated by a short segment of five amino acids. J. Biol. Chem. 266: 3107–3112, 1991.
 50. Dalman, F. C., E. H. Bresnick, P. D. Patel, G. H. Perdew, S. J. Watson, and W. B. Pratt. Direct evidence that the glucocorticoid receptor binds to hsp90 at or near the termination of receptor translation in vitro. J. Biol. Chem. 64: 9815–9821, 1989.
 51. Dalman, F. C., E. R. Sanchez, A. L. Y. Lin, F. Perini, and W. B. Pratt. Localization of phosphorylation sites with respect to the functional domains of the mouse L cell glucocorticoid receptor. J. Biol. Chem. 263: 12259–12267, 1988.
 52. Dalman, F. C., L. C. Scherrer, L. P. Taylor, H. Akil, and W. B. Pratt. Localization of the 90–kDa heat shock protein–binding site within the hormone‐binding domain of the glucocorticoid receptor by peptide competition. J. Biol. Chem. 266: 3482–3490, 1991.
 53. Daniel, V., A. B. Maksymowych, E. S. Alnemri, and G. Litwack. Cell‐free synthesis of rat glucocorticoid receptor in rabbit reticulocyte lysate. In vitro synthesis of receptor in Mr 90,000 heat shock protein–depleted lysate. J. Biol. Chem. 266: 1320–1325, 1991.
 54. Danielsen, M., L. Hinck, G. M. Ringold. Two amino acids within the knuckle of the first zinc finger specify DNA response element activation by the glucocorticoid receptor. Cell 57: 1131–1138, 1989.
 55. Danielsen, M., J. P. Northrop, and G. M. Ringold. The mouse glucocorticoid receptor: mapping of functional domains by cloning, sequencing and expression of wild‐type and mutant receptor proteins. EMBO J. 5: 2513–2522, 1986.
 56. Dauvois, S., P. S. Danielian, R. White, and M. G. Parker. Antiestrogen ICI 164,384 reduces cellular estrogen receptor content by increasing its turnover. Proc. Natl. Acad. Sci. U.S.A. 89: 4037–4041, 1992.
 57. Davidoff, A. M., P. A. Humphrey, J. D. Iglehart, and J. R. Marks. Genetic basis for p53 overexpression in human breast cancer. Proc. Natl. Acad. Sci., U.S.A. 88: 5006–5010, 1991.
 58. Davis, R. J. The mitogen‐activated protein kinase signal transduction pathway. J. Biol. Chem. 268: 14553–14556, 1993.
 59. Denis, M., and J. A. Gustafsson. Translation of glucocorticoid receptor mRNA in vitro yields a nonactivated protein. J. Biol. Chem. 264: 6005–6008, 1989.
 60. Denis, M., J. A. Gustafsson, and A. C. Wikstrom. Interaction of the Mr = 90,000 heat shock protein with the steroid‐binding domain of the glucocorticoid receptor. J. Biol. Chem. 263: 18520–18523, 1988.
 61. Denner, L. A., W. T. Schrader, B. W. O'Malley, and N. L. Weigel. Hormonal regulation and identification of chicken progesterone receptor phosphorylation sites. J. Biol. Chem. 265: 16548–16555, 1990.
 62. Denner, L. A., N. L. Weigel, B. L. Maxwell, W. T. Schrader, and B. W. O'Malley. Regulation of progesterone receptor–mediated transcription by phosphorylation. Science 250: 1740–1743, 1990.
 63. Denton, R. R., N. J. Koszewski, and A. C. Notides. Estrogen receptor phosphorylation: hormonal dependence and consequence on specific DNA binding. J. Biol. Chem. 267: 7263–7268, 1992.
 64. Distelhorst, C. W., and K. J. Howard. Evidence from pulse‐chase labeling studies that the antiglucocorticoid hormone RU486 stabilizes the nonactivated form of the glucocorticoid receptor in mouse lymphoma cells. J. Steroid Biochem. 36: 25–31, 1990.
 65. Dobson, A. D. W., O. M. Conneely, W. Beattie, B. L. Maxwell, P. Mak, M. J. Tsai, W. T. Schrader, and B. W. O'Malley. Mutational analysis of the chicken progesterone receptor. J. Biol. Chem. 264: 4207–4211, 1989.
 66. Edelman, I. S., R. Bogoroch, and G. A. Porter. On the mechanism of action of aldosterone on sodium transport: the role of protein synthesis. Proc. Natl. Acad. Sci. U.S.A. 50: 1169–1177, 1963.
 67. Eilers, M., D. Picard, K. R. Yamamoto, and J. M. Bishop. Chimaeras of myc oncoprotein and steroid receptors cause hormone‐dependent transformation of cells. Nature 340: 66–68, 1989.
 68. El‐Ashry, D., S. A. Onate, S. K. Nordeen, and D. P. Edwards. Human progesterone receptor complexed with the antagonist RU486 binds to hormone response elements in a structurally altered form. Mol. Endocrinol. 3: 1545–1558, 1989.
 69. Eliezer, N., C. B. Hurd, and V. K. Moudgil. Immunologically distinct binding molecules for progesterone and RU38486 in the chick oviduct cytosol. Biochim. Biophys. Acta 929: 34–39, 1987.
 70. Encio, I. J., and S. D. Detera‐Wadleigh. The genomic structure of the human glucocorticoid receptor. J. Biol. Chem. 266: 7182–7188, 1991.
 71. Ennis, B. W., W. E. Stumpf, J. M. Gasc, and E. E. Baulieu. Nuclear localization of progesterone receptor before and after exposure to progestin at low and high temperatures: autoradiographic and immunohistological studies of chick oviduct. Endocrinology 119: 2066–2075, 1986.
 72. Evans, R. M. The steroid and thyroid hormone receptor superfamily. Science 240: 889–895, 1988.
 73. Evans, R. M. Molecular characterization of the glucocorticoid receptor. Recent Prog. Horm. Res. 45: 1–27, 1989.
 74. Evans, R. M., and S. M. Hollenberg. Zinc fingers: gilt by association. Cell 52: 1–3, 1988.
 75. Fawell, S. E., J. A. Lees, R. White, and M. Parker. Characterization and colocalization of steroid binding and dimerization activities in the mouse estrogen receptor. Cell 60: 953–962, 1990.
 76. Fawell, S. E., R. White, S. Hoare, M. Sydenham, M. Page, and M. G. Parker. Inhibition of estrogen receptor–DNA binding by the “pure” antiestrogen ICI 164,384 appears to be mediated by impaired receptor dimerization. Proc. Natl. Acad. Sci. U.S.A. 87: 6883–6887, 1990.
 77. Formstecher, P., P. Lefebvre, and M. Dautrevaux. RU 486 stabilizes the glucocorticoid receptor in a non‐transformed high molecular weight form in intact thymus cells under physiological conditions. J. Steroid Biochem. 31: 607–612, 1990.
 78. Foster, J. S. and J. Wimalasena. Estrogen regulates activity of cyclin‐dependent kinases and retinoblastoma protein phosphorylation in breast cancer cells. Mol. Endocrinol. 10: 488–498, 1996.
 79. Freedman, L. P., B. F. Luisi, Z. R. Korzun, R. Basavappa, P. B. Sigler, and K. R. Yamamoto. The function and structure of the metal coordination sites within the glucocorticoid receptor DNA binding domain. Nature 334: 543–546, 1988.
 80. Freiss, G., and F. Vignon. Antiestrogens increase protein tyrosine phosphatase activity in human breast cancer cells. Mol. Endocrinol. 8: 1389–1396, 1994.
 81. Fujimoto, N., and B. S. Katzenellenbogen. Alteration in the agonist/antagonist balance of antiestrogens by activation of protein kinase A signalling pathways in breast cancer cells: antiestrogen selectivity and promoter dependence. Mol. Endocrinol. 8: 296–304, 1994.
 82. Garcia, M., D. Derocq, G. Freiss, and H. Rochefort. Activation of estrogen receptor transfected into a receptor‐negative breast cancer cell line decreases the metastatic and invasive potential of the cells. Proc. Natl. Acad. Sci. U.S.A. 89: 11538–11542, 1992.
 83. Gehring, U., and H. Arndt. Heteromeric nature of glucocorticoid receptors. FEBS Lett. 179: 138–142, 1985.
 84. Geier, A., R. Bella, R. Beery, M. Haimsohn, and B. Lunenfeld. Differences in the association of the progesterone receptor ligated by antiprogestin RU38486 or progestin ORG 2058 to chromatin components. Biochim. Biophys. Acta 931: 78–86, 1987.
 85. Giguere, V., S. M. Hollenberg, and R. M. Evans. Functional domains of the human glucocorticoid receptor. Cell 46: 645–652, 1986.
 86. Glass, C. K. Differential recognition of target genes by nuclear receptor monomers, dimers, and heterodimers. Endocr. Rev. 15: 391–407, 1994.
 87. Godowski, P. J., and D. Picard. Steroid receptors. How to be both a receptor and a transcription factor. Biochem. Pharmacol. 38: 3135–3143, 1989.
 88. Godowski, P. J., D. Picard, and K. R. Yamamoto. Signal transduction and transcriptional regulation by glucocorticoid receptor‐lex A fusion proteins. Science 241: 812–816, 1988.
 89. Godowski, P. J., S. Rusconi, R. Meisfeld, and K. R. Yamamoto. Glucocorticoid receptor mutants that are constitutive activators of transcriptional enhancement. Nature 325: 365–368, 1987.
 90. Gorospe, M., S. Shack, K. Z. Guyton, D. Samid, and N. J. Holbrook. Up regulation and functional role of p21 (WAF1/CIP1) during growth arrest of human breast carcinoma MCF‐7 cells by phenylacetate. Cell growth and differentiation 7: 1609–1615, 1996.
 91. Govindan, M. J., M. Devic, S. Green, H. Gronemeyer, and P. Chambon. Cloning of the human glucocorticoid receptor cDNA. Nucleic Acids Res. 13: 8293–8304, 1985.
 92. Grandics, P., A. Miller, T. J. Schmidt, D. Mittman, and G. Litwack. Purification of the unactivated glucocorticoid receptor and its subsequent in vitro activation. J. Biol. Chem. 259: 3173–3180, 1984.
 93. Gray, G. O., and W. W. Leavitt. RU486 is not an antiprogestin in the hamster. J. Steroid Biochem. 28: 493–497, 1987.
 94. Green, S., and P. Chambon. Oestradiol induction of a glucocorticoid‐responsive gene by a chimaeric receptor. Nature 325: 75–78, 1987.
 95. Green, S., and P. Chambon. Nuclear receptors enhance our understanding of transcription regulation. Trends Genet. 4: 309–314, 1988.
 96. Green, S., and P. Chambon. Chimeric receptors used to probe the DNA‐binding domain of the estrogen and glucocorticoid receptors. Cancer Res. 49: 2282s–2285s, 1989.
 97. Green, S., V. Kumar, I. Theulaz, W. Wahli, and P. Chambon. The n‐terminal DNA‐binding “zinc finger” of the oestrogen and glucocorticoid receptors determines target gene specificity. EMBO J. 7: 3037–3044, 1988.
 98. Greene, G. L., P. Gilna, M. Waterfield, A. Baker, Y. Hort, and J. Shine. Sequence and expression of human estrogen receptor complimentary DNA. Science 231: 1150–1154, 1986.
 99. Gronemeyer, H., B. Benhamou, M. Berry, M. T. Bocquel, D. Gofflo, T. Garcia, T. Lerouge, D. Metzger, M. E. Meyer, L. Tora, A. Vergezac, and P. Chambon. Mechanisms of antihormone action. J. Steroid Biochem. Mol. Biol. 41: 217–221, 1992.
 100. Gronemeyer, H., B. Turcotte, C. Quirin‐Stricker, M. T. Bocquel, M. E. Meyer, Z. Krozowski, J. M. Jeltsch, T. Lerouge, J. M. Garnier, and P. Chambon. The chicken progesterone receptor: Sequence, expression and functional analysis. EMBO J. 6: 3985–3994, 1987.
 101. Groyer, A., Y. Le Bouc, I. Joab, C. Radanyi, J. M. Renoir, P. Robel, and E. E. Baulieu. Chick oviduct glucocorticosteroid receptor. Specific binding of the synthetic steroid RU486 and immunological studies with antibodies to chick oviduct progesterone receptor. Eur. J. Biochem. 149: 445–451, 1985.
 102. Groyer, A., G. Schweizer‐Groyer, F. Cadepond, M. Mariller, and E. E. Baulieu. Antiglucocorticosteroid effects suggest why steroid hormone is required for receptors to bind DNA in vivo but not in vitro. Nature 328: 624–626, 1987.
 103. Guiochon‐Mantel, A., H. Loosfelt, P. Lescop, S. Sar, M. Atger, M. Perrot‐Applanat, and E. Milgrom. Mechanism of nuclear localization of the progesterone receptor: evidence for interaction between monomers. Cell 57: 1147–1154, 1989.
 104. Guiochon‐Mantel, A., H. Loosfelt, T. Ragot, A. Bailly, M. Atger, M. Misrahi, M. Perricaudet, and E. Milgrom. Receptors bound to antiprogestin form abortive complexes with hormone responsive elements. Nature 336: 695–698, 1988.
 105. Halachmi, S., E. Marden, G. Martin, H. MacKay, C. Abbondanza, and M. Brown. Estrogen receptor–associated proteins: possible mediators of hormone‐induced transcription. Science 264: 1455–1458, 1994.
 106. Ham, J., and M. G. Parker. Regulation of gene expression by nuclear hormone receptors. Curr. Opin. Cell Biol. 1: 503–511, 1989.
 107. Ham, J., A. Thompson, M. Needham, P. Webb, and M. Parker. Characterization of response elements for androgens, glucocorticoids and progestins in mouse mammary tumor virus. Nucleic Acids Res. 16: 5263–5276, 1988.
 108. Hard, T., K. Dahlman, J. Carlstedt‐Duke, J. A. Gustafsson, and R. Rigler. Cooperativity and specificity in the interactions between DNA and the glucocorticoid receptor DNA‐binding domain. Biochemistry 29: 5358–5364, 1990.
 109. Hard, T., E. Kellenbach, R. Boelens, B. A. Maler, K. Dahlman, L. P. Freedman, J. Carlstedt‐Duke, K. R. Yamamoto, J. A. Gustafsson, and R. Kaptein. Solution structure of the glucocorticoid receptor DNA‐binding domain. Science 249: 157–160, 1990.
 110. Harris, C. C. p53: at the crossroads of molecular carcinogenesis and risk assessment. Science 262: 1980–1981, 1993.
 111. Henderson, B. E., R. K. Ross, and M. C. Pike. Hormonal chemoprevention of cancer in women. Science 259: 633–638, 1993.
 112. Hill, C. S., and R. Treisman. Transcriptional regulation by extra‐cellular signals: mechanisms and specificity. Cell 80: 199–211, 1995.
 113. Hoeck, W., and B. Groner. Hormone‐dependent phosphorylation of the glucocorticoid receptor occurs mainly in the amino‐terminal transactivation domain. J. Biol. Chem. 265: 5403–5408, 1990.
 114. Hoeck, W., S. Rusconi, and B. Groner. Down‐regulation and phosphorylation of glucocorticoid receptors in cultured cells. Investigations with a monospecific antiserum against a bacterially expressed receptor fragment. J. Biol. Chem. 264: 14396–14402, 1989.
 115. Hollenberg, S. M., and R. M. Evans. Multiple and cooperative transactivation domains of the human glucocorticoid receptor. Cell 55: 899–906, 1988.
 116. Hollenberg, S. M., V. Giguere, and R. M. Evans. Identification of two regions of the human glucocorticoid receptor hormone binding domain that block activation. Cancer Res. 49: 2292s–2294s, 1989.
 117. Hollenberg, S. M., C. Weinberger, E. S. Ong, G. Cerelli, A. Oro, R. Lebo, E. B. Thompson, M. G. Rosenfeld, and R. M. Evans. Primary structure and expression of a functional human glucocorticoid receptor cDNA. Nature 318: 635–641, 1985.
 118. Horwitz, K. B. The antiprogestin RU38486: receptor‐mediated progestin versus antiprogestin actions screened in estrogen‐insensitive T47Dco human breast cancer cells. Endocrinology 116: 2236–2245, 1985.
 119. Horwitz, K. B. How do breast cancers become hormone resistant. J. Steroid Biochem. Mol. Biol. 49: 295–302, 1994.
 120. Howard, K. J., S. J. Holley, K. R. Yomamoto, and C. W. Distelhorst. Mapping the hsp90 binding region of the glucocorticoid receptor. J. Biol. Chem. 265: 11928–11935, 1990.
 121. Hsieh, J. C., P. W. Jurutka, M. A. Galligan, C. M. Terpening, C. A. Haussler, D. S. Samuels, Y. Shimizu, N. Shimizu, and M. R. Haussler. Human vitamin D receptor is selectively phosphorylated by protein kinase C on serine 51, a residue crucial to its trans‐activation function. Proc. Natl. Acad. Sci. U.S.A. 88: 9315–9319, 1991.
 122. Hsieh, J. C., P. W. Jurutka, S. Nakajima, M. A. Galligan, C. A. Haussler, Y. Shimizu, N. Shimizu, G. K. Whitfield, and M. Haussler. Phosphorylation of the human vitamin D receptor by protein kinase C: biochemical and functional evaluation of the serine 51 recognition site. J. Biol. Chem. 268: 15118–15126, 1993.
 123. Huckaby, C. S., O. M. Conneely, W. G. Beattie, A. D. W. Dobson, M. J. Tsai, and B. W. O'Malley. Structure of the chromosomal chicken progesterone receptor gene. Proc. Natl. Acad. Sci. U.S.A. 84: 8380–8384, 1987.
 124. Hunter, T. A thousand and one protein kinases. Cell 50: 823–829, 1987.
 125. Hunter, T. Protein kinases and phosphatases: the yin and yang of protein phosphorylation and signaling. Cell 80: 225–236, 1995.
 126. Hunter, T., and M. Karin. The regulation of transcription by phosphorylation. Cell 70: 375–387, 1992.
 127. Hupp, T. R., D. W. Meek, C. A. Midgley, and D. P. Lane. Regulation of the specific DNA binding function of p53. Cell 71: 875–886, 1992.
 128. Hurd, C., N. Khattree, P. Alban, K. Nag, S. C. Jhanwar, S. Dinda, and V. K. Moudgil. Hormonal regulation of the p53 tumor suppressor protein in T47D human breast carcinoma cell line. J. Biol. Chem. 270: 28507–28510, 1995.
 129. Hurd, C., N. Khattree, S. Dinda, P. Alban and V. K. Moudgil. Regulation of tumor suppressor proteins, p53 and retinoblastoma, by estrogen and antiestrogens in breast cancer cells. Oncogene, 15: 991–995, 1997.
 130. Hurd, C., and V. K. Moudgil. Characterization of R5020 and RU486 binding to progesterone receptor from the calf uterus. Biochemistry 27: 3618–3623, 1988.
 131. Hurd, C., M. Nakao, and V. K. Moudgil. Phosphorylation of calf uterine progesterone receptor by cAMP‐dependent protein kinase. Biochem. Biophys. Res. Commun. 162: 160–167, 1989.
 132. Hutchison, K. A., K. D. Dittmar, M. J. Czar, and W. B. Pratt. Proof that hsp70 is required for assembly of the glucocorticoid receptor into heterocomplex with hsp90. J. Biol. Chem. 269: 5043–5049, 1994.
 133. Ince, B. A., M. M. Montano, and B. S. Katzenellenbogen. Activation of transcriptionally inactive human estrogen receptors by cyclic adenosine 3′,5′‐monophosphate and ligands including antiestrogens. Mol. Endocrinol. 8: 1397–1406, 1994.
 134. Ing, N. H., J. M. Beekman, S. Y. Tsai, M. J. Tsai, and B. W. O'Malley. Members of the steroid hormone receptor superfamily interact with TFIIB (S300–II). J. Biol. Chem. 267: 17617–17623, 1992.
 135. Jackson, P., D. Baltimore, and D. Picard. Hormone‐conditional transformation by fusion proteins of c‐Abl and its transforming variants. EMBO J. 12: 2809–2819, 1993.
 136. Jacq, X., C. Brou, Y. Lutz, I. Davidson, P. Chambon, and L. Tora. Human TAFII30 is present in a distinct TFIID complex and is required for transcriptional activation by the estrogen receptor. Cell 79: 107–117, 1994.
 137. Jensen, E. V., and H. T. Jacobson. Basic guides to the mechanisms of estrogen actions. Recent Prog. Horm. Res. 18: 387–414, 1962.
 138. Jensen, E. V., T. Suzuki, T. Kawashima, W. E. Stumpf, P. W. Jungblut, and E. R. Desombre. A two‐step mechanism for the interaction of estradiol with rat uterus. Proc. Natl. Acad. Sci., U.S.A. 59: 632–638, 1968.
 139. Joel, P. B., A. M. Traish, and D. A. Lannigan. Estradiol and phorbol ester cause phosphorylation of serine 118 in human estrogen receptor. Mol. Endocrinol. 9: 1041–1052, 1995.
 140. Jurutka, P. W., J. C. Hsieh, P. N. MacDonald, C. M. Terpening, C. A. Haussler, M. R. Haussler, and G. K. Whitfield. Phosphorylation of serine 208 in the human vitamin D receptor: the predominant amino acid phosphorylated by casein kinase II, in vitro, and identification as a significant phosphorylation site in intact cells. J. Biol. Chem. 268: 6791–6799, 1993.
 141. Kalderon, D., W. D. Richardson, A. F. Markham, and A. E. Smith. Sequence requirements for nuclear location of simian virus 40 large‐T antigen. Nature 311: 33–38, 1984.
 142. Kasid, A., M. E. Lippman, A. G. Papageorge, D. R. Lowy, and E. P. Gelmann. Transfection of v‐ras DNA into MCF‐7 human breast cancer cells bypasses dependence on estrogen for tumorigenicity. Science 228: 725–728, 1985.
 143. Kato, S., H. Endoh, Y. Masuhiro, T. Kitamoto, S. Uchiyama, H. Sasaki, S. Masushige, Y. Gotoh, E. Nishida, H. Kawashima, D. Metzger, and P. Chambon. Activation of the estrogen receptor through phosphorylation by mitogen‐activated protein kinase. Science 270: 1491–1494, 1995.
 144. King, W. J., and G. L. Greene. Monoclonal antibodies localize oestrogen receptor in the nuclei of target cells. Nature 307: 745–747, 1984.
 145. Klein‐Hitpass, L., A. C. B. Cato, D. Henderson, and G. U. Ryffel. Two types of antiprogestins identified by their differential action in transcriptionally active extracts from T47D cells. Nucleic Acids Res. 19: 1227–1234, 1991.
 146. Koike, S., M. Sakai, and M. Muramatsu. Molecular cloning and characterization of rat estrogen receptor cDNA. Nucleic Acids Res. 5: 2499–2513, 1987.
 147. Kost, S. L., D. F. Smith, W. P. Sullivan, W. J. Welch, and D. O. Toft. Binding of heat shock proteins to the avian progesterone receptor. Mol. Cell. Biol. 9: 3829–3838, 1989.
 148. Koyasu, S., E. Nishida, T. Kadowaki, F. Matsuzaki, K. Iida, F. Harada, M. Kasuga, H. Sakai, and I. Yahara. Two mammalian heat shock proteins, hsp90 and hsp100, are actin‐binding proteins. Proc. Natl. Acad. Sci. U.S.A. 83: 8054–8058, 1986.
 149. Krust, A., S. Green, P. Argos, V. Kumar, P. Walter, J. M. Bornert, and P. Chambon. The chicken oestrogen receptor sequence: homology with v‐erb‐A and the human oestrogen and glucocorticoid receptors. EMBO J. 5: 891–897, 1986.
 150. Kumar, V., and P. Chambon. The estrogen receptor binds tightly to its responsive element as a ligand‐induced homodimer. Cell 55: 145–156, 1988.
 151. Kumar, V., S. Green, G. Stack, M. Berry, L. R. Jin, and P. Chambon. Functional domains of the human estrogen receptor. Cell 51: 941–951, 1987.
 152. Kumar, V., S. Green, A. Staub, and P. Chambon. Localisation of the oestradiol‐binding and putative DNA‐binding domains of the human oestrogen receptor. EMBO J. 5: 2231–2236, 1986.
 153. Lane, D. P. p53, guardian of the genome. Nature 358: 15–16, 1992.
 154. Lefebvre, P., P. M. Danze, B. Sablonniere, C. Richard, P. Formstecher, and M. Dautrevaux. Association of the glucocorticoid receptor binding subunit with the 90K non‐steroid binding component is stabilized by both steroidal and nonsteroidal antiglucocorticoids in intact cells. Biochemistry 27: 9186–9194, 1988.
 155. Le Goff, P., M. M. Montano, D. J. Schodin, and B. S. Katzenellenbogen. Phosphorylation of the human estrogen receptor: identification of hormone‐regulated sites and examination of their influence on transcriptional activity. J. Biol. Chem. 269: 4458–4466, 1994.
 156. Levenson, A. S., and V. C. Jordan. Transfection of human estrogen receptor (ER) cDNA into ER‐negative mammalian cell lines. J. Steroid Biochem. Mol. Biol. 51: 229–239, 1994.
 157. Levine, A. J., J. Momand, and C. A. Finlay. The p53 tumor suppressor gene. Nature 351: 453–456, 1991.
 158. Li, W., and R. E. Handschumacher. Specific interaction of the cyclophilin–cyclosporin complex with the B subunit of calcineurin. J. Biol. Chem. 268: 14040–14044, 1993.
 159. Lindquist, S., and E. A. Craig. The heat shock proteins. Annu. Rev. Genet. 22: 631–677, 1988.
 160. Logeat, F., M. Le Cunff, R. Pamphile, and E. Milgrom. The nuclear‐bound form of the progesterone receptor is generated through a hormone‐dependent phosphorylation. Biochem. Biophys. Res. Commun. 31: 421–427, 1985.
 161. Loosfelt, H., M. Atger, M. Misrahi, A. Guiochon‐Mantel, C. Meriel, F. Logeat, R. Benarous, and E. Milgrom. Cloning and sequence analysis of rabbit progesterone‐receptor complimentary DNA. Proc. Natl. Acad. Sci. U.S.A. 83: 9045–9049, 1986.
 162. Lowe, S. W., S. Bodis, A. McClatchey, L. Remington, H. E. Ruley, D. E. Fisher, D. E. Housman, and T. Jacks. p53 status and the efficacy of cancer therapy in vivo. Science 266: 807–810, 1994.
 163. Lowe, S. W., H. E. Ruley, T. Jacks, and D. E. Housman. p53‐dependent apoptosis modulates the cytotoxicity of anticancer agents. Cell 74: 957–967, 1993.
 164. Lubahn, D. B., D. R. Joseph, P. M. Sullivan, H. F. Willard, F. S. French, and E. M. Wilson. Cloning of human androgen receptor complimentary DNA and localization to the X chromosome. Science 240: 327–330, 1988.
 165. Luisi, B. F., W. X. Xu, Z. Otwinowski, L. P. Freedman, K. R. Yamamoto, and P. B. Sigler. Crystallographic analysis of the interaction of the glucocorticoid receptor with DNA. Nature 352: 497–505, 1991.
 166. Lukas, J., J. Bartkova, and J. Bartek. Convergence of mitogenic signalling cascades from diverse classes of receptors at the cyclin D–cyclin‐dependent kinase–pRB‐controlled G1 checkpoint. Mol. Cell. Biol. 16: 6917–6925, 1996.
 167. Luttrell, D. K., A. Lee, T. J. Lansing, R. M. Crosby, K. D. Jung, D. Willard, M. Luther, M. Rodriguez, J. Berman, and T. M. Gilmer. Involvement of pp60c‐src with two major signalling pathways in human breast cancer. Proc. Natl. Acad. Sci. U.S.A. 91: 83–87, 1994.
 168. Mader, S., V. Kumar, H. de Verneuil, and P. Chambon. Three amino acids of the oestrogen receptor are essential to its ability to distinguish an oestrogen from a glucocorticoid‐responsive element. Nature 338: 271–274, 1989.
 169. Mangelsdorf, D. J., C. Thummel, M. Beato, P. Herrich, G. Schuts, K. Umesono, B. Blumberg, P. Kastner, M. Mark, P. Chambon, and R. M. Evans. The nuclear receptor superfamily: the second decade. Cell 83: 835–839, 1995.
 170. Mason, S. A., and P. R. Housley. Site‐directed mutagenesis of the phosphorylation sites in the mouse glucocorticoid receptor. J. Biol. Chem. 268: 21501–21504, 1993.
 171. Matsuda, S., Y. Kadowaki, M. Ichino, T. Akiyama, K. Toyoshima, and T. Yamamoto. 17β‐Estradiol mimics ligand activity of the c‐erbB2 protooncogene product. Proc. Natl. Acad. Sci., U.S.A. 90: 10803–10807, 1993.
 172. Meinkoth, J. L., Y. Ji, S. S. Taylor, and J. R. Feramisco. Dynamics of the distribution of cyclic AMP‐dependent protein kinase in living cells. Proc. Natl. Acad. Sci. U.S.A. 87: 9595–9599, 1990.
 173. Metzger, D., M. Berry, S. Ali, and P. Chambon. Effect of antagonists on DNA binding properties of the human estrogen receptor in vitro and in vivo. Mol. Endocrinol. 9: 579–591, 1995.
 174. Meyer, M. E., A. Pornon, J. Ji, M. T. Bocquel, P. Chambon, and H. Gronemeyer. The agonist and antagonist activities of RU486 on the functions of the human progesterone receptor. EMBO J. 9: 3923–3932, 1990.
 175. Miesfeld, R., S. Rusconi, P. J. Godowski, B. A. Maler, S. Okret, A. C. Wikstrom, J. A. Gustafsson, and K. R. Yamamoto. Genetic complimentation of a glucocorticoid receptor deficiency by expression of cloned receptor cDNA. Cell 46: 389–399, 1986.
 176. Migliaccio, A., M. Di Domenico, S. Green, A. de Falco, E. L. Kajtaniak, F. Blasi, P. Chambon, and F. Auricchio. Phosphorylation on tyrosine of in vitro synthesized human estrogen receptor activates its hormone binding. Mol. Endocrinol. 3: 1061–1069, 1989.
 177. Migliaccio, A., M. Pagano, and F. Auricchio. Immediate and transient stimulation of protein tyrosine phosphorylation by estradiol in MCF‐7 cells. Oncogene 8: 2183–2191, 1993.
 178. Migliaccio, A., A. Rotondi, and F. Auricchio. Calmodulin‐stimulated phosphorylation of 17β‐estradiol receptor on tyrosine. Proc. Natl. Acad. Sci., U.S.A. 81: 5921–5925, 1984.
 179. Migliaccio, A., A. Rotondi, and F. Auricchio. Estradiol receptor: phosphorylation on tyrosine in uterus and interaction with anti‐phosphotyrosine antibody. EMBO J. 5: 2867–2872, 1986.
 180. Milad, M., W. Sullivan, E. Diehl, M. Altmann, S. Nordeen, D. P. Edwards, and D. O. Toft. Interaction of the progesterone receptor with binding proteins for FK506 and cyclosporin A. Mol. Endocrinol. 9: 838–847, 1995.
 181. Miller, M. M., C. Hurd, and V. K. Moudgil. Transformation of human progesterone receptor in the presence of the progestin (R5020) and the antiprogestin (RU486). J. Steroid Biochem. 31: 777–783, 1988.
 182. Milne, D. M., R. H. Palmer, and D. W. Meek. Mutation of the casein kinase II phosphorylation site abolishes the antiproliferative activity of p53. Nucleic Acids Res. 520: 5565–5570, 1992.
 183. Misrahi, M., M. Atger, L. d'Auriol, H. Loosfelt, C. Meriel, F. Fridlansky, A. Guiochon‐Mantel, F. Galibert, and E. Milgrom. Complete amino acid sequence of the human progesterone receptor deduced from cloned cDNA. Biochem. Biophys. Res. Commun. 143: 740–748, 1987.
 184. Moguilewsky, M., and D. Philibert. RU38486: potent antiglucocorticoid activity correlated with strong binding to the cytosolic glucocorticoid receptor followed by an impaired activation. J. Steroid Biochem. 1: 271–276, 1984.
 185. Moll, U. M., G. Riou, and A. J. Levine. Two distinct mechanisms alter p53 in breast cancer: mutation and nuclear exclusion. Proc. Natl. Acad. Sci., U.S.A. 89: 7262–7266, 1992.
 186. Montano, M. M., V. Muller, A. Trobaugh, and B. S. Katzenellenbogen. The carboxy‐terminal F domain of the human estrogen receptor and the transcriptional activity of the receptor and the effectiveness of antiestrogens as estrogen antagonists. Mol. Endocrinol. 9: 814–825, 1995.
 187. Moudgil, V. K. Phosphorylation of steroid hormone receptors. Biochim. Biophys. Acta 1055: 243–258, 1990.
 188. Moudgil, V. K., M. J. Anter, and C. Hurd. Mammalian progesterone receptor shows differential sensitivity to sulfhydryl group modifying agents when bound to agonist and antagonist ligands. J. Biol. Chem. 264: 2203–2211, 1989.
 189. Moudgil, V. K., and M. Gunda. Hepatic glucocorticoid receptor behaves differently when its hormone binding site is occupied by agonist (triamcinolone acetonide) or antagonist (RU486) steroid ligands. Biochem. Biophys. Res. Commun. 174: 1239–1247, 1991.
 190. Moudgil, V. K., and C. Hurd. Transformation of calf uterine progesterone receptor: analysis of the process when receptor is bound to progesterone and RU486. Biochemistry 26: 4993–5001, 1987.
 191. Moudgil, V. K., G. Lombardo, C. Hurd, N. Eliezer, and M. K. Agarwal. Evidence for separate binding sites for progesterone and RU486 in the chick oviduct. Biochim. Biophys. Acta 889: 192–199, 1986.
 192. Musgrove, E. A., C. S. L. Lee, A. L. Cornish, A. Swarbrick, and R. L. Sutherland. Antiprogestin inhibition of cell cycle progression in T‐47D breast cancer cells is accompanied by induction of the cyclin‐dependent kinase inhibitor p21. Mol. Endocrinol. 11: 54–66, 1997.
 193. Nakao, M., T. Mizutani, A. Bhakta, N. Ribarac‐Stepic, and V. K. Moudgil. Phosphorylation of chicken oviduct progesterone receptor by cAMP‐dependent protein kinase. Arch. Biochem. Biophys. 298: 340–348, 1992.
 194. Nakao, M., and V. K. Moudgil. Hormone specific phosphorylation and transformation of chicken oviduct progesterone receptor. Biochem. Biophys. Res. Commun. 164: 295–303, 1989.
 195. Nielsen, C. J., J. J. Sando, and W. B. Pratt. Evidence that dephosphorylation inactivates glucocorticoid receptors. Proc. Natl. Acad. Sci. U.S.A. 74: 1398–1402, 1977.
 196. Ning, Y. M., and E. R. Sanchez. Potentiation of glucocorticoid receptor–mediated gene expression by the immunophilin ligands FK506 and rapamycin. J. Biol. Chem. 268: 6073–6076, 1993.
 197. Nordeen, S. K., B. J. Bona, and M. L. Moyer. Latent agonist activity of the steroid antagonist, RU486, is unmasked in cells treated with activators of protein kinase A. Mol. Endocrinol. 7: 731–742, 1993.
 198. Northrop, J. P., B. Gametchu, R. W. Harrison, and G. M. Ringold. Characterization of wild type and mutant glucocorticoid receptors from rat hepatoma and mouse lymphoma cells. J. Biol. Chem. 260: 6398–6403, 1985.
 199. Noteboom, W. D., and J. Gorski. An early effect of estrogen on protein synthesis. Proc. Natl. Acad. Sci. U.S.A. 50: 250–255, 1963.
 200. Notides, A. C., N. Lerner, and D. E. Hamilton. Positive cooperatively of the estrogen receptor. Proc. Natl. Acad. Sci. U.S.A. 78: 4926–4930, 1981.
 201. Ohara‐Nemoto, Y., P. E. Stromstedt, K. Dahlman‐Wright, T. Nemoto, J. A. Gustafsson, and J. Carlstedt‐Duke. The steroid‐binding properties of recombinant glucocorticoid receptor: a putative role for heat shock protein hsp90. J. Steroid Biochem. Mol. Biol. 37: 481–490, 1990.
 202. Okret, S., A. C. Wikstrom, and J. A. Gustafsson. Molybdate‐stabilized glucocorticoid receptor: evidence for a receptor heteromer. Biochemistry 24: 6581–6586, 1985.
 203. O'Malley, B. W., M. R. Sherman, and D. O. Toft. Progesterone receptors in the cytoplasm and nucleus of chick oviduct target tissue. Proc. Natl. Acad. Sci. U.S.A. 67: 501–509, 1970.
 204. Onate, S. A., S. Y. Tsai, M. J. Tsai, and B. W. O'Malley. Sequence and characterization of a coactivator for the steroid hormone receptor superfamily. Science 270: 1354–357, 1995.
 205. Orti, E., J. E. Bodwell, and A. Munck. Phosphorylation of steroid hormone receptors. Endocr. Rev. 13: 105–128, 1992.
 206. Orti, E., D. B. Mendel, L. I. Smith, and A. Munck. Agonist‐dependent phosphorylation and nuclear dephosphorylation of glucocorticoid receptors in intact cells. J. Biol. Chem. 264: 9728–9731, 1989.
 207. Pasqualini, J. R. Breast cancer, present and future. J. Steroid Biochem. Mol. Biol. 51: V–VI, 1994.
 208. Pelham, H. R. B. Speculations on the functions of the major heat shock and glucose‐regulated proteins. Cell 46: 959–961, 1986.
 209. Perrot‐Applanat, M., F. Logeat, M. T. Groyer‐Picard, and E. Milgrom. Immunocytochemical study of mammalian progesterone receptor using monoclonal antibodies. Endocrinology 116: 1473–1484, 1985.
 210. Pfahl, M. Nuclear receptor/AP‐1 interaction. Endocr. Rev. 14: 651–658, 1993.
 211. Philibert, D. RU38486: an original multifaceted antihormone in vivo. In: Adrenal Steroid Antagonism, edited by M. K. Agarwal. New York: de Gruyter, 1984, p. 77–101.
 212. Picard, D., B. Khursheed, M. J. Garabedian, M. G. Fortin, S. Lindquist, and K. R. Yamamoto. Reduced levels of hsp90 compromise steroid receptor action in vivo. Nature 348: 166–168, 1990.
 213. Picard, D., S. J. Salser, and K. R. Yamamoto. A movable and regulable inactivation function within the steroid binding domain of the glucocorticoid receptor. Cell 54: 1073–1080, 1988.
 214. Picard, D., and K. R. Yamamoto. Two signals mediate hormone‐dependent nuclear localization of the glucocorticoid receptor. EMBO J. 6: 3333–3340, 1987.
 215. Pike, J. W., and N. M. Sleator. Hormone‐dependent phosphorylation of the 1, 25–di‐hydroxyvitamin D3 receptor in mouse fibroblasts. Biochem. Biophys. Res. Commun. 131: 378–385, 1985.
 216. Ponglikitmongkol, M., S. Green, and P. Chambon. Genomic organization of the human oestrogen receptor gene. EMBO J. 7: 3385–3388, 1988.
 217. Power, R. F., S. K. Mani, J. Codina, O. M. Conneely, and B. W. O'Malley. Dopaminergic and ligand‐independent activation of steroid hormone receptors. Science 254: 1636–1639, 1991.
 218. Pratt, W. B. Transformation of glucocorticoid and progesterone receptors to the DNA‐binding state. J. Cell. Biochem. 35: 51–68, 1987.
 219. Pratt, W. B. The role of heat shock proteins in regulating the function, folding, and trafficking of the glucocorticoid receptor. J. Biol. Chem. 268: 21455–21458, 1993.
 220. Pratt, W. B., D. J. Jolly, D. V. Pratt, S. M. Hollenberg, V. Giguere, F. M. Cadepond, G. Schweizer‐Groyer, M. G. Catelli, R. M. Evans, and E. E. Baulieu. A region in the steroid binding domain determines formation of the non‐DNA‐binding, 9S glucocorticoid receptor complex. J. Biol. Chem. 263: 267–273, 1988.
 221. Rajpert, E. J., F. P. Lemaigre, P. H. Eliard, M. Place, D. A. Lafontaine, I. V. Economidis, A. Belayew, J. A. Martial, and G. G. Rousseau. Glucocorticoid receptors bound to the antagonist RU486 are not downregulated despite their capacity to interact in vitro with defined gene regions. J. Steroid Biochem. 26: 513–520, 1987.
 222. Rauch, M., H. Loosfelt, D. Philibert, and E. Milgrom. Mechanism of action of an antiprogesterone, RU486, in the rabbit endometrium. Effects of RU486 on the progesterone receptor and on the uteroglobin gene. Eur. J. Biochem. 148: 213–218, 1985.
 223. Reddel, R. R., I. E. Alexander, M. Koga, J. Shine, and R. L. Sutherland. Genetic instability and the development of steroid hormone insensitivity in cultured T47D human breast cancer cells. Cancer Res. 48: 4340–4347, 1988.
 224. Reese, J. C., and B. S. Katzenellenbogen. Differential DNA‐binding abilities of estrogen receptor occupied with two classes of antiestrogens: studies using human estrogen receptor overexpressed in mammalian cells. Nucleic Acids Res. 19: 6595–6602, 1991.
 225. Reese, J. C., and B. S. Katzenellenbogen. Examination of the DNA‐binding ability of estrogen receptor in whole cells: implications for hormone‐independent transactivation and the actions of antiestrogens. Mol. Cell. Biol. 12: 4531–4538, 1992.
 226. Rehberger, P., M. Rexin, and U. Gehring. Heterotetrameric structure of the human progesterone receptor. Proc. Natl. Acad. Sci. U.S.A. 89: 8001–8005, 1992.
 227. Reichmann, E., H. Schwarz, E. M. Deiner, I. Leitner, M. Eilers, J. Berger, M. Busslinger, and H. Beug. Activation of an inducible c‐fosER fusion protein causes loss of epithelial polarity and triggers epithelial‐fibroblastoid cell conversion. Cell 71: 1103–1116, 1992.
 228. Renoir, J. M., T. Buchou, J. Mester, C. Radanyi, and E. E. Baulieu. Oligomeric structure of molybdate‐stabilized, non‐transformed 8S progesterone receptor from chicken oviduct cytosol. Biochemistry 23: 6016–6023, 1984.
 229. Renoir, J. M., C. Radanyi, L. E. Faber, and E. E. Baulieu. The non‐DNA binding heterooligomeric form of mammalian steroid hormone receptors contains a hsp90–bound 59–kilodalton protein. J. Biol. Chem. 265: 10740–10745, 1990.
 230. Renoir, J. M., C. Radanyi, I. Jung‐Testas, L. E. Faber, and E. E. Baulieu. The nonactivated progesterone receptor is a nuclear heterooligomer. J. Biol. Chem. 265: 14402–4406, 1990.
 231. Roemer, K., and T. Friedmann. Modulation of cell proliferation and gene expression by a p53–estrogen receptor hybrid protein. Proc. Natl. Acad. Sci. U.S.A. 90: 9252–9256, 1993.
 232. Rose, D. W., W. J. Welch, G. Kramer, and B. Hardesty. Possible involvement of the 90–kDa heat shock protein in the regulation of protein synthesis. J. Biol. Chem. 264: 6239–6244, 1989.
 233. Rothman, J. E. Polypeptide chain binding proteins: catalysts of protein folding and related processes in cells. Cell 59: 591–601, 1989.
 234. Rusconi, S., and K. R. Yamamoto. Functional dissection of the hormone and DNA binding activities of the glucocorticoid receptor. EMBO J. 6: 1309–1315, 1987.
 235. Sablonniere, B., P. M. Danze, P. Formstecher, P. Lefebvre, and M. Dautrevaux. Physical characterization of the activated and non‐activated forms of the glucocorticoid‐receptor complex bound to the steroid antagonist [3H]RU486. J. Steroid Biochem. 25: 605–614, 1986.
 236. Sanchez, E. R. Hsp 56: a novel heat shock protein associated with untransformed steroid receptor complexes. J. Biol. Chem. 265: 22067–22070, 1990.
 237. Sanchez, E. R., L. E. Faber, W. J. Henzel. and W. B. Pratt. 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 protein. Biochemistry 29: 5145–5152, 1990.
 238. Sartorius, C. A., S. D. Groshong, L. A. Miller, R. L. Powell, L. Tung, G. S. Takimoto, and K. B. Horwitz. New T47D breast cancer cell lines for the independent study of progesterone B‐ and A‐receptors: only antiprogestin‐occupied B‐receptors are switched to transcriptional agonists by cAMP. Cancer Res. 54: 3868–3877, 1994.
 239. Sartorius, C. A., M. Y. Melville, A. R. Hovland, L. Tung, G. S. Takimoto, and K. B. Horwitz. A third transactivation function (AF3) of human progesterone receptors located in the unique n‐terminal segment of the B‐isoform. Mol. Endocrinol. 8: 1347–1360, 1994.
 240. Sartorius, C. A., L. Tung, G. S. Takimoto, and K. B. Horwitz. Antagonist‐occupied human progesterone receptors bound to DNA are functionally switched to transcriptional agonists by cAMP. J. Biol. Chem. 268: 9262–9266, 1993.
 241. Savouret, J. F., M. Misrahi, H. Loosfelt, M. Atger, A. Bailly, M. Perrot‐Applanat, M. T. Vu Hai, A. Guiochon‐Mantel, A. Jolivet, F. Lorenzo, F. Logeat, M. F. Pichon, P. Bouchard, and E. Milgrom. Molecular and cellular biology of mammalian progesterone receptors. Recent Prog. Horm. Res. 45: 65–120, 1989.
 242. Schauer, M., G. Chalepakis, T. Willmann, and M. Beato. Binding of hormone accelerates the kinetics of glucocorticoid and progesterone receptor binding to DNA. Proc. Natl. Acad. Sci. U.S.A. 86: 1123–1127, 1989.
 243. Schena, M., and K. R. Yamamoto. Mammalian glucocorticoid receptor derivatives enhance transcription in yeast. Science 241: 965–967, 1988.
 244. Schmidt, T. J. In vitro activation and DNA binding affinity of human lymphoid (CEM‐C7) cytoplasmic receptors labeled with the antiglucocorticoid RU38486. J. Steroid Biochem. 24: 853–863, 1986.
 245. Schuchard, M., J. P. Landers, N. P. Sandhu, and T. C. Spelsberg. Steroid hormone regulation of nuclear proto‐oncogenes. Endocr. Rev. 14: 659–669, 1993.
 246. Schwabe, J. W. R., L. Chapman, J. T. Finch, and D. Rhodes. The crystal structure of the estrogen receptor DNA‐binding domain bound to DNA: how receptors discriminate between their response elements. Cell 75: 567–578, 1993.
 247. Schwabe, J. W. R., D. Neuhaus, and D. Rhodes. Solution structure of the DNA‐binding domain of the oestrogen receptor. Nature 348: 458–461, 1990.
 248. Segniz, B., and U. Gehring. Mechanism of action of a steroidal antiglucocorticoid in lymphoid cells. J. Biol. Chem. 265: 2789–2796, 1990.
 249. Sheridan, P. L., R. M. Evans, and K. B. Horwitz. Phosphotryptic peptide analysis of human progesterone receptors. New phosphorylated sites formed in nuclei after hormone treatment. J. Biol. Chem. 264: 6520–6528, 1989.
 250. Sheridan, P. L., M. D. Francis, and K. B. Horwitz. Synthesis of human progesterone receptors in T47D cells. Nascent A‐ and B‐translational maturation step. J. Biol. Chem. 264, 7054–7058, 1989.
 251. Sheridan, P. L., N. L. Krett, J. A. Gordon, and K. B. Horwitz. Human progesterone receptor transformation and nuclear down‐regulation are independent of phosphorylation. Mol. Endocrinol. 2: 1329–1342, 1988.
 252. Sicinski, P., J. L. Donaher, S. B. Parker, T. Li, A. Fazeli, H. Gardner, S. Z. Haslam, R. T. Bronson, S. J. Elledge, and R. A. Weinberg. Cyclin D1 provides a link between development and oncogenesis in the retina and breast. Cell 82: 621–630, 1995.
 253. Simental, J. A., M. Sar, M. V. Lane, F. S. French, and E. M. Wilson. Transcriptional activation and nuclear targeting signals of the human androgen receptor. J. Biol. Chem. 266: 510–518, 1991.
 254. Singh, P., J. Coe, and W. Hong. A role for retinoblastoma protein in potentiating transcriptional activation by the glucocorticoid receptor. Nature 374: 562–565, 1995.
 255. Smith, D. F. Dynamics of heat shock protein 90–progesterone receptor binding and disactivation loop model for steroid receptor complexes. Mol. Endocrinol. 7: 1418–1429, 1993.
 256. Smith, D. F., L. E. Faber, and D. O. Toft. Purification of unactivated progesterone receptor and identification of novel receptor‐associated proteins. J. Biol. Chem. 265: 3996–4003, 1990.
 257. Smith, D. F., and D. O. Toft. Steroid receptors and their associated proteins. Mol. Endocrinol. 7: 4–11, 1993.
 258. Smith, D. F., D. B. Schowalter, S. L. Kost, and D. O. Toft. Reconstitution of progesterone receptor with heat shock proteins. Mol. Endocrinol. 4: 1704–1711, 1990.
 259. Smith, L. I., D. B. Mendel, J. E. Bodwell, and A. Munck. Phosphorylated sites within the functional domains of the 100‐kDa steroid‐binding subunit of glucocorticoid receptors. Biochemistry 8: 4490–4498, 1989.
 260. Strahle, U., G. Klock, and G. Schutz. A DNA sequence of 15 base pairs is sufficient to mediate both glucocorticoid and progesterone induction of gene expression. Proc. Natl. Acad. Sci. U.S.A. 84: 7871–7875, 1987.
 261. Sullivan, W. P., B. J. Madden, D. J. McCormick, and D. O. Toft. Hormone‐dependent phosphorylation of the avian progesterone receptor. J. Biol. Chem. 263: 14717–14723, 1988.
 262. Superti‐Furga, G., G. Bergers, D. Picard, and M. Busslinger. Hormone‐dependent transcriptional regulation and cellular transformation by fos‐steroid receptor fusion proteins. Proc. Natl. Acad. Sci. U.S.A. 88: 5114–5118, 1991.
 263. Szyszka, R., G. Kramer, and B. Hardesty. The phosphorylation state of the reticulocyte 90‐kDa heat shock protein affects its ability to increase phosphorylation of peptide initiation factor 2 alpha subunit by the heme‐sensitive kinase. Biochemistry 28: 1435–1438, 1989.
 264. Tai, P. K. K., M. W. Albers, H. Chang, L. E. Faber, and S. L. Schreiber. Association of a 59–kilodalton immunophilin with the glucocorticoid receptor complex. Science 256: 1315–1318, 1992.
 265. Tai, P. K. K., M. W. Albers, D. P. McDonnell, H. Chang, S. L. Schreiber, and L. E. Faber. Potentiation of progesterone receptor–mediated transcription by the immunosuppressant FK506. Biochemistry 33: 10666–10671, 1994.
 266. Tai, P. K. K., Y. Maeda, K. Nakao, N. G. Wakim, J. L. Duhring, and L. E. Faber. A 59‐kilo‐dalton protein associated with progestin, estrogen, androgen, and glucocorticoid receptors. Biochemistry 25: 5269–5275, 1986.
 267. Takimoto, G. S., D. M. Tasset, A. C. Eppert, and K. B. Horwitz. Hormone‐induced progesterone receptor phosphorylation consists of sequential DNA‐independent and DNA‐dependent stages: analysis with zinc finger mutants and the progesterone antagonist ZK98299. Proc. Natl. Acad. Sci. U.S.A. 89: 3050–3054, 1992.
 268. Tasset, D., L. Tora, C. Fromental, E. Scheer, and P. Chambon. Distinct classes of transcriptional activating domains function by different mechanisms. Cell 62: 1177–1187, 1990.
 269. Teutsch, G. 11 Beta‐substituted 19–norsteroids: at the crossroads between hormone agonists and antagonists. In: Adrenal Steroid Antagonism, edited by M. K. Agarwal. New York: deGruyter, 1984, p. 43–75.
 270. Teutsch, G., T. Ojasoo, and J. P. Raynaud. 11β‐Substituted steroids, an original pathway to antihormones. J. Steroid Biochem. 31: 549–565, 1988.
 271. Thompson, E. B. Apoptosis and steroid hormones. Mol. Endocrinol. 8: 665–673, 1994.
 272. Tilley, W. D., M. Marcelli, J. D. Wilson, and M. J. McPhaul. Characterization and expression of a cDNA encoding the human androgen receptor. Proc. Natl Acad. Sci. U.S.A. 86: 327–331, 1989.
 273. Toft, D. O., and J. Gorski. A receptor molecule for estrogens: isolation from the rat uterus and preliminary characterization. Proc. Natl. Acad. Sci. U.S.A. 55: 574–1581, 1966.
 274. Tora, L., H. Gronemeyer, B. Turcotte, M. P. Gaub, and P. Chambon. The n‐terminal region of the chicken progesterone receptor specifies target gene activation. Nature 333: 185–188, 1988.
 275. Tora, L., A. Mullick, D. Metzger, M. Ponglikitmongkol, I. Park, and P. Chambon. The cloned human oestrogen receptor contains a mutation which alters its hormone binding properties. EMBO J. 8: 1981–1986, 1989.
 276. Tora, L., J. White, C. Brou, D. Tasset, N. Webster, E. Scheer, and P. Chambon. The human estrogen receptor has two independent nonacidic transcriptional activation functions. Cell 59: 477–487, 1989.
 277. Trapman, J., P. Klaassen, G. G. J. M. Kuiper, J. A. G. M. van der Korput, P. W. Faber, H. C. J. van Rooij, A. Geurts van Kessel, M. M. Voorhorst, E. Mulder, and A. O. Brinkmann. Cloning, structure and expression of a cDNA encoding the human androgen receptor. Biochem. Biophys. Res. Commun. 153: 241–248, 1988.
 278. Truss, M., and M. Beato. Steroid hormone receptors: interaction with deoxyribonucleic acid and transcription factors. Endocr. Rev. 14: 459–479, 1993.
 279. Truss, M., J. Bartsch, and M. Beato. Antiprogestins prevent progesterone receptor binding to responsive elements in vivo. Proc. Natl. Acad. Sci. U.S.A. 91: 11333–11337, 1994.
 280. Tsai, M. J., S. Y. Tsai, L. Klein‐Hitpass, M. Bagchi, J. F. Elliston, J. Carlstedt‐Duke, J. K. Gustafsson, and B. W. O'Malley. Cooperative interactions of steroid hormone receptors with their cognate response elements. Cold Spring Harb. Symp. Quant. Biol. 53: 829–833, 1988.
 281. Tsai, S. Y., J. Carlstedt‐Duke, N. L. Weigel, K. Dahlman, J. A. Gustafsson, M. J. Tsai, and B. W. O'Malley. Molecular interactions of steroid hormone receptor with its enhancer element: evidence for receptor dimer formation. Cell 55: 361–369, 1988.
 282. Tung, L., M. K. Mohamed, J. P. Hoeffler, G. S. Takimoto, and K. B. Horwitz, K. B. Horwitz Antagonist‐occupied human progesterone B‐receptors activate transcription without binding to progesterone response elements and are dominantly inhibited by A‐receptors. Mol. Endocrinol. 7: 1256–1265, 1993.
 283. Turcotte, B., M. E. Meyer, M. T. Bocquel, L. Belanger, and P. Chambon. Repression of the alpha‐fetoprotein gene promoter by progesterone and chimeric receptors in the presence of hormones and antihormones. Mol. Cell. Biol. 10: 5002–5006, 1990.
 284. Umesono, K., and R. M. Evans. Determinants of target gene specificity for steroid/thyroid hormone receptors. Cell 57: 1139–1146, 1989.
 285. Van Laar, J. H., C. A. Berrevoets, J. Trapman, N. D. Zegers, and A. O. Brinkmann. Hormone‐dependent androgen receptor phosphorylation is accompanied by receptor transformation in human lymph node carcinoma of the prostate cells. J. Biol. Chem. 266: 3734–3738, 1991.
 286. Vegeto, E., M. M. Shahbaz, D. X. Wen, M. E. Goldman, B. W. O'Malley, and D. P. McDonnell. Human progesterone receptor A form is a cell‐ and promoter‐specific repressor of human progesterone receptor B function. Mol. Endocrinol. 7: 1244–1255, 1993.
 287. Vojtesek, B., and D. P. Lane. Regulation of p53 protein expression in human breast cancer cell lines. J. Cell Sci. 105: 607–612, 1993.
 288. Walker, A. I., T. Hunt, R. J. Jackson, and C. W. Anderson. Double‐stranded DNA induces the phosphorylation of several proteins including the 90 000 mol. wt. heat‐shock protein in animal cell extracts. EMBO J. 4: 139–145, 1985.
 289. Walter, P., S. Green, G. Greene, A. Krust, J. M. Bornert, L. M. Jeltsch, A. Staub, E. Jensen, G. Scrace, M. Waterfield, and P. Chambon. Cloning of the human estrogen receptor cDNA. Proc. Natl. Acad. Sci. U.S.A. 82: 7889–7893, 1985.
 290. Wang, Y., and C. Prives. Increased and altered DNA binding of human p53 by S and G2/M but not G1 cyclin‐dependent kinases. Nature 376: 88–91, 1995.
 291. Watts, C. K. W., A. Brady, B. Sarcevic, A. de Fazio, E. A. Musgrove, and R. L. Sutherland. Antiestrogen inhibition of cell cycle progression in breast cancer cells is associated with inhibition of cyclin‐dependent kinase activity and decreased retinoblastoma proteinphosphorylation. Mol. Endocrinol. 9: 1804–1813, 1995.
 292. Webster, N. J. G., S. Green, J. R. Jin, and P. Chambon. The hormone‐binding domains of the estrogen and glucocorticoid receptors contain an inducible transcription activation function. Cell 54: 199–207, 1988.
 293. Wegener, A. D., and L. R. Jones. Phosphorylation‐induced mobility shift in phospholambin in sodium dodecyl sulfate‐polyacrylamide gels. J. Biol. Chem. 259: 1834–1841, 1984.
 294. Wei, L. L., P. L. Sheridan, N. L. Krett, M. D. Francis, D. O. Toft, D. P. Edwards, and K. B. Horwitz. Immunological analysis of human breast cancer progesterone receptors. 2. Structure, phosphorylation, and processing. Biochemistry 26: 6262–6272, 1987.
 295. Weigel, N. L., J. S. Tash, A. R. Means, W. T. Schrader, and B. W. O'Malley. Phosphorylation of hen progesterone receptor by cAMP‐dependent protein kinase. Biochem. Biophys. Res. Commun. 102: 513–519, 1981.
 296. Weinberg, R. A. The retinoblastoma protein and cell cycle control. Cell 81: 323–330, 1995.
 297. Weinberger, C., S. M. Hollenberg, M. G. Rosenfeld, and R. M. Evans. Domain structure of human glucocorticoid receptor and its relationship to the v‐erb‐A oncogene product. Nature 318: 670–672, 1985.
 298. Weintraub, S. J., K. N. B. Chow, R. X. Luo, S. H. Zhang, S. He, and D. C. Dean. Mechanism of active transcriptional repression by the retinoblastoma protein. Nature 375: 812–815, 1995.
 299. Welshons, W. V., B. M. Krummel, and J. Gorski. Nuclear localization of unoccupied receptors for glucocorticoids, estrogens, and progesterone in GH3 cells. Endocrinology 117: 2140–2147, 1985.
 300. White, E. p53, guardian of Rb. Nature 371: 21–22, 1994.
 301. Wrange, O., P. Eriksson, and T. Perlmann. The purified activated glucocorticoid receptor is a homodimer. J. Biol. Chem. 264: 5253–5259, 1989.
 302. Xu, Y., and S. Lindquist. Heat‐shock protein hsp90 governs the activity of pp60V‐src kinase. Proc. Natl. Acad. Sci. U.S.A. 90: 7074–7078, 1993.
 303. Yamamoto, K. R. Steroid receptor regulated transcription of specific genes and gene networks. Annu. Rev. Genet. 19: 209–252, 1985.
 304. Yamamoto, K. R., P. J. Godowski, and D. Picard. Ligand‐regulated nonspecific inactivation of receptor function: a versatile mechanism for signal transduction. Cold Spring Harb. Symp. Quant. Biol. 53: 803–811, 1988.
 305. Yoshinaga, S. K., C. L. Peterson, I. Herskowitz, and K. R. Yamamoto. Roles of SWI1, SWI2, and SWI3 proteins for transcriptional enhancement by steroid receptors. Science 258: 1598–1603, 1992.
 306. Zhang, Y., C. A. Beck, A. Poletti, D. P. Edwards, and N. L. Weigel. Identification of phosphorylation sites unique to the B form of human progesterone receptor: in vitro phosphorylation by casein kinase II. J. Biol. Chem. 269: 31034–31040, 1994.
 307. Zhang, Y., C. A. Beck, A. Poletti, D. P. Edwards, and N. L. Weigel. Identification of a group of ser‐pro motif hormone‐inducible phosphorylation sites in the human progesterone receptor. Mol. Endocrinol. 9: 1029–1040, 1995.
 308. Zilliacus, J., K. Dahlman‐Wright, A. Wright, J. A. Gustafsson, and J. Carlstedt‐Duke. DNA binding specificity of mutant glucocorticoid receptor DNA‐binding domains. J. Biol. Chem. 266: 3101–3106, 1991.
 309. Zilliacus, J., A. P. H. Wright, J. Carlstedt‐Duke, and J. A. Gustafsson. Structural determinants of DNA‐binding specificity by steroid receptors. Mol. Endocrinol. 9: 389–400, 1995.

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Cliff Hurd, V. K. Moudgil. Steroid Hormone Receptor Families. Compr Physiol 2011, Supplement 20: Handbook of Physiology, The Endocrine System, Cellular Endocrinology: 383-411. First published in print 1998. doi: 10.1002/cphy.cp070115