Skip to main content
Molecular and Cellular Biology logoLink to Molecular and Cellular Biology
. 1994 Sep;14(9):5756–5765. doi: 10.1128/mcb.14.9.5756

Functional evidence for ligand-dependent dissociation of thyroid hormone and retinoic acid receptors from an inhibitory cellular factor.

J Casanova 1, E Helmer 1, S Selmi-Ruby 1, J S Qi 1, M Au-Fliegner 1, V Desai-Yajnik 1, N Koudinova 1, F Yarm 1, B M Raaka 1, H H Samuels 1
PMCID: PMC359101  PMID: 8065310

Abstract

The ligand-binding domains of thyroid hormone (L-triiodothyronine [T3]) receptors (T3Rs), all-trans retinoic acid (RA) receptors (RARs), and 9-cis RA receptors (RARs and RXRs) contain a series of heptad motifs thought to be important for dimeric interactions. Using a chimera containing amino acids 120 to 392 of chicken T3R alpha (cT3R alpha) positioned between the DNA-binding domain of the yeast GAL4 protein and the potent 90-amino-acid transactivating domain of the herpes simplex virus VP16 protein (GAL4-T3R-VP16), we provide functional evidence that binding of ligand releases T3Rs and RARs from an inhibitory cellular factor. GAL4-T3R-VP16 does not bind T3 and does not activate transcription from a GAL4 reporter when expressed alone but is able to activate transcription when coexpressed with unliganded T3R or RAR. This activation is reversed by T3 or RA, suggesting that these receptors compete with GAL4-T3R-VP16 for a cellular inhibitor and that ligand reverses this effect by dissociating T3R or RAR from the inhibitor. A chimera containing the entire ligand-binding domain of cT3R alpha (amino acids 120 to 408) linked to VP16 [GAL4-T3R(408)-VP16] is activated by unliganded receptor as well as by T3. In contrast, GAL4-T3R containing the amino acid 120 to 408 ligand-binding region without the VP16 domain is activated only by T3. The highly conserved ninth heptad, which is involved in heterodimerization, appears to participate in the receptor-inhibitor interaction, suggesting that the inhibitor is a related member of the receptor gene family. In striking contrast to T3R and RAR, RXR activates GAL4-T3R-VP16 only with its ligand, 9-cis RA, but unliganded RXR does not appear to be the inhibitor suggested by these studies. Further evidence that an orphan receptor may be the inhibitor comes from our finding that COUP-TF inhibits activation of GAL4-T3R-VP16 by unliganded T3R and the activation of GAL4-T3R by T3. These and other results suggest that an inhibitory factor suppresses transactivation by the T3Rs and RARs while these receptors are bound to DNA and that ligands act, in part, by inactivating or promoting dissociation of a receptor-inhibitor complex.

Full text

PDF
5756

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Allan G. F., Leng X., Tsai S. Y., Weigel N. L., Edwards D. P., Tsai M. J., O'Malley B. W. Hormone and antihormone induce distinct conformational changes which are central to steroid receptor activation. J Biol Chem. 1992 Sep 25;267(27):19513–19520. [PubMed] [Google Scholar]
  2. Andersson M. L., Nordström K., Demczuk S., Harbers M., Vennström B. Thyroid hormone alters the DNA binding properties of chicken thyroid hormone receptors alpha and beta. Nucleic Acids Res. 1992 Sep 25;20(18):4803–4810. doi: 10.1093/nar/20.18.4803. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Au-Fliegner M., Helmer E., Casanova J., Raaka B. M., Samuels H. H. The conserved ninth C-terminal heptad in thyroid hormone and retinoic acid receptors mediates diverse responses by affecting heterodimer but not homodimer formation. Mol Cell Biol. 1993 Sep;13(9):5725–5737. doi: 10.1128/mcb.13.9.5725. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Baniahmad A., Ha I., Reinberg D., Tsai S., Tsai M. J., O'Malley B. W. Interaction of human thyroid hormone receptor beta with transcription factor TFIIB may mediate target gene derepression and activation by thyroid hormone. Proc Natl Acad Sci U S A. 1993 Oct 1;90(19):8832–8836. doi: 10.1073/pnas.90.19.8832. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Baniahmad A., Köhne A. C., Renkawitz R. A transferable silencing domain is present in the thyroid hormone receptor, in the v-erbA oncogene product and in the retinoic acid receptor. EMBO J. 1992 Mar;11(3):1015–1023. doi: 10.1002/j.1460-2075.1992.tb05140.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Baniahmad A., Steiner C., Köhne A. C., Renkawitz R. Modular structure of a chicken lysozyme silencer: involvement of an unusual thyroid hormone receptor binding site. Cell. 1990 May 4;61(3):505–514. doi: 10.1016/0092-8674(90)90532-j. [DOI] [PubMed] [Google Scholar]
  7. Baniahmad A., Tsai S. Y., O'Malley B. W., Tsai M. J. Kindred S thyroid hormone receptor is an active and constitutive silencer and a repressor for thyroid hormone and retinoic acid responses. Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10633–10637. doi: 10.1073/pnas.89.22.10633. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Bedo G., Santisteban P., Aranda A. Retinoic acid regulates growth hormone gene expression. Nature. 1989 May 18;339(6221):231–234. doi: 10.1038/339231a0. [DOI] [PubMed] [Google Scholar]
  9. Berrodin T. J., Marks M. S., Ozato K., Linney E., Lazar M. A. Heterodimerization among thyroid hormone receptor, retinoic acid receptor, retinoid X receptor, chicken ovalbumin upstream promoter transcription factor, and an endogenous liver protein. Mol Endocrinol. 1992 Sep;6(9):1468–1478. doi: 10.1210/mend.6.9.1331778. [DOI] [PubMed] [Google Scholar]
  10. Brent G. A., Dunn M. K., Harney J. W., Gulick T., Larsen P. R., Moore D. D. Thyroid hormone aporeceptor represses T3-inducible promoters and blocks activity of the retinoic acid receptor. New Biol. 1989 Dec;1(3):329–336. [PubMed] [Google Scholar]
  11. Bresnick E. H., Dalman F. C., Sanchez E. R., Pratt W. B. Evidence that the 90-kDa heat shock protein is necessary for the steroid binding conformation of the L cell glucocorticoid receptor. J Biol Chem. 1989 Mar 25;264(9):4992–4997. [PubMed] [Google Scholar]
  12. Bugge T. H., Pohl J., Lonnoy O., Stunnenberg H. G. RXR alpha, a promiscuous partner of retinoic acid and thyroid hormone receptors. EMBO J. 1992 Apr;11(4):1409–1418. doi: 10.1002/j.1460-2075.1992.tb05186.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Carey M., Kakidani H., Leatherwood J., Mostashari F., Ptashne M. An amino-terminal fragment of GAL4 binds DNA as a dimer. J Mol Biol. 1989 Oct 5;209(3):423–432. doi: 10.1016/0022-2836(89)90007-7. [DOI] [PubMed] [Google Scholar]
  14. Carson-Jurica M. A., Schrader W. T., O'Malley B. W. Steroid receptor family: structure and functions. Endocr Rev. 1990 May;11(2):201–220. doi: 10.1210/edrv-11-2-201. [DOI] [PubMed] [Google Scholar]
  15. Casanova J., Horowitz Z. D., Copp R. P., McIntyre W. R., Pascual A., Samuels H. H. Photoaffinity labeling of thyroid hormone nuclear receptors. Influence of n-butyrate and analysis of the half-lives of the 57,000 and 47,000 molecular weight receptor forms. J Biol Chem. 1984 Oct 10;259(19):12084–12091. [PubMed] [Google Scholar]
  16. Cooney A. J., Leng X., Tsai S. Y., O'Malley B. W., Tsai M. J. Multiple mechanisms of chicken ovalbumin upstream promoter transcription factor-dependent repression of transactivation by the vitamin D, thyroid hormone, and retinoic acid receptors. J Biol Chem. 1993 Feb 25;268(6):4152–4160. [PubMed] [Google Scholar]
  17. Cooney A. J., Tsai S. Y., O'Malley B. W., Tsai M. J. Chicken ovalbumin upstream promoter transcription factor (COUP-TF) dimers bind to different GGTCA response elements, allowing COUP-TF to repress hormonal induction of the vitamin D3, thyroid hormone, and retinoic acid receptors. Mol Cell Biol. 1992 Sep;12(9):4153–4163. doi: 10.1128/mcb.12.9.4153. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Dahlman-Wright K., Siltala-Roos H., Carlstedt-Duke J., Gustafsson J. A. Protein-protein interactions facilitate DNA binding by the glucocorticoid receptor DNA-binding domain. J Biol Chem. 1990 Aug 15;265(23):14030–14035. [PubMed] [Google Scholar]
  19. Dalman F. C., Koenig R. J., Perdew G. H., Massa E., Pratt W. B. In contrast to the glucocorticoid receptor, the thyroid hormone receptor is translated in the DNA binding state and is not associated with hsp90. J Biol Chem. 1990 Mar 5;265(7):3615–3618. [PubMed] [Google Scholar]
  20. Damm K., Thompson C. C., Evans R. M. Protein encoded by v-erbA functions as a thyroid-hormone receptor antagonist. Nature. 1989 Jun 22;339(6226):593–597. doi: 10.1038/339593a0. [DOI] [PubMed] [Google Scholar]
  21. Desai-Yajnik V., Samuels H. H. The NF-kappa B and Sp1 motifs of the human immunodeficiency virus type 1 long terminal repeat function as novel thyroid hormone response elements. Mol Cell Biol. 1993 Aug;13(8):5057–5069. doi: 10.1128/mcb.13.8.5057. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Evans R. M. The steroid and thyroid hormone receptor superfamily. Science. 1988 May 13;240(4854):889–895. doi: 10.1126/science.3283939. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Flug F., Copp R. P., Casanova J., Horowitz Z. D., Janocko L., Plotnick M., Samuels H. H. cis-acting elements of the rat growth hormone gene which mediate basal and regulated expression by thyroid hormone. J Biol Chem. 1987 May 5;262(13):6373–6382. [PubMed] [Google Scholar]
  24. Forman B. M., Casanova J., Raaka B. M., Ghysdael J., Samuels H. H. Half-site spacing and orientation determines whether thyroid hormone and retinoic acid receptors and related factors bind to DNA response elements as monomers, homodimers, or heterodimers. Mol Endocrinol. 1992 Mar;6(3):429–442. doi: 10.1210/mend.6.3.1316541. [DOI] [PubMed] [Google Scholar]
  25. Forman B. M., Samuels H. H. Interactions among a subfamily of nuclear hormone receptors: the regulatory zipper model. Mol Endocrinol. 1990 Sep;4(9):1293–1301. doi: 10.1210/mend-4-9-1293. [DOI] [PubMed] [Google Scholar]
  26. Forman B. M., Samuels H. H. pEXPRESS: a family of expression vectors containing a single transcription unit active in prokaryotes, eukaryotes and in vitro. Gene. 1991 Aug 30;105(1):9–15. doi: 10.1016/0378-1119(91)90507-8. [DOI] [PubMed] [Google Scholar]
  27. Forman B. M., Yang C. R., Au M., Casanova J., Ghysdael J., Samuels H. H. A domain containing leucine-zipper-like motifs mediate novel in vivo interactions between the thyroid hormone and retinoic acid receptors. Mol Endocrinol. 1989 Oct;3(10):1610–1626. doi: 10.1210/mend-3-10-1610. [DOI] [PubMed] [Google Scholar]
  28. Forman B. M., Yang C. R., Stanley F., Casanova J., Samuels H. H. c-erbA protooncogenes mediate thyroid hormone-dependent and independent regulation of the rat growth hormone and prolactin genes. Mol Endocrinol. 1988 Oct;2(10):902–911. doi: 10.1210/mend-2-10-902. [DOI] [PubMed] [Google Scholar]
  29. Geffner M. E., Su F., Ross N. S., Hershman J. M., Van Dop C., Menke J. B., Hao E., Stanzak R. K., Eaton T., Samuels H. H. An arginine to histidine mutation in codon 311 of the C-erbA beta gene results in a mutant thyroid hormone receptor that does not mediate a dominant negative phenotype. J Clin Invest. 1993 Feb;91(2):538–546. doi: 10.1172/JCI116233. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Glass C. K., Devary O. V., Rosenfeld M. G. Multiple cell type-specific proteins differentially regulate target sequence recognition by the alpha retinoic acid receptor. Cell. 1990 Nov 16;63(4):729–738. doi: 10.1016/0092-8674(90)90139-6. [DOI] [PubMed] [Google Scholar]
  31. Glass C. K., Lipkin S. M., Devary O. V., Rosenfeld M. G. Positive and negative regulation of gene transcription by a retinoic acid-thyroid hormone receptor heterodimer. Cell. 1989 Nov 17;59(4):697–708. doi: 10.1016/0092-8674(89)90016-0. [DOI] [PubMed] [Google Scholar]
  32. Godowski P. J., Picard D., Yamamoto K. R. Signal transduction and transcriptional regulation by glucocorticoid receptor-LexA fusion proteins. Science. 1988 Aug 12;241(4867):812–816. doi: 10.1126/science.3043662. [DOI] [PubMed] [Google Scholar]
  33. Hamada K., Gleason S. L., Levi B. Z., Hirschfeld S., Appella E., Ozato K. H-2RIIBP, a member of the nuclear hormone receptor superfamily that binds to both the regulatory element of major histocompatibility class I genes and the estrogen response element. Proc Natl Acad Sci U S A. 1989 Nov;86(21):8289–8293. doi: 10.1073/pnas.86.21.8289. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Hodin R. A., Lazar M. A., Chin W. W. Differential and tissue-specific regulation of the multiple rat c-erbA messenger RNA species by thyroid hormone. J Clin Invest. 1990 Jan;85(1):101–105. doi: 10.1172/JCI114398. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Hodin R. A., Lazar M. A., Wintman B. I., Darling D. S., Koenig R. J., Larsen P. R., Moore D. D., Chin W. W. Identification of a thyroid hormone receptor that is pituitary-specific. Science. 1989 Apr 7;244(4900):76–79. doi: 10.1126/science.2539642. [DOI] [PubMed] [Google Scholar]
  36. Holloway J. M., Glass C. K., Adler S., Nelson C. A., Rosenfeld M. G. The C'-terminal interaction domain of the thyroid hormone receptor confers the ability of the DNA site to dictate positive or negative transcriptional activity. Proc Natl Acad Sci U S A. 1990 Oct;87(20):8160–8164. doi: 10.1073/pnas.87.20.8160. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Horowitz Z. D., Sahnoun H., Pascual A., Casanova J., Samuels H. H. Analysis of photoaffinity label derivatives to probe thyroid hormone receptor in human fibroblasts, GH1 cells, and soluble receptor preparations. J Biol Chem. 1988 May 15;263(14):6636–6642. [PubMed] [Google Scholar]
  38. Horowitz Z. D., Yang C. R., Forman B. M., Casanova J., Samuels H. H. Characterization of the domain structure of chick c-erbA by deletion mutation: in vitro translation and cell transfection studies. Mol Endocrinol. 1989 Jan;3(1):148–156. doi: 10.1210/mend-3-1-148. [DOI] [PubMed] [Google Scholar]
  39. Härd T., Kellenbach E., Boelens R., Maler B. A., Dahlman K., Freedman L. P., Carlstedt-Duke J., Yamamoto K. R., Gustafsson J. A., Kaptein R. Solution structure of the glucocorticoid receptor DNA-binding domain. Science. 1990 Jul 13;249(4965):157–160. doi: 10.1126/science.2115209. [DOI] [PubMed] [Google Scholar]
  40. Ing N. H., Beekman J. M., Tsai S. Y., Tsai M. J., O'Malley B. W. Members of the steroid hormone receptor superfamily interact with TFIIB (S300-II). J Biol Chem. 1992 Sep 5;267(25):17617–17623. [PubMed] [Google Scholar]
  41. Katz D., Lazar M. A. Dominant negative activity of an endogenous thyroid hormone receptor variant (alpha 2) is due to competition for binding sites on target genes. J Biol Chem. 1993 Oct 5;268(28):20904–20910. [PubMed] [Google Scholar]
  42. Kliewer S. A., Umesono K., Heyman R. A., Mangelsdorf D. J., Dyck J. A., Evans R. M. Retinoid X receptor-COUP-TF interactions modulate retinoic acid signaling. Proc Natl Acad Sci U S A. 1992 Feb 15;89(4):1448–1452. doi: 10.1073/pnas.89.4.1448. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Kliewer S. A., Umesono K., Mangelsdorf D. J., Evans R. M. Retinoid X receptor interacts with nuclear receptors in retinoic acid, thyroid hormone and vitamin D3 signalling. Nature. 1992 Jan 30;355(6359):446–449. doi: 10.1038/355446a0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Lazar M. A., Berrodin T. J. Thyroid hormone receptors form distinct nuclear protein-dependent and independent complexes with a thyroid hormone response element. Mol Endocrinol. 1990 Nov;4(11):1627–1635. doi: 10.1210/mend-4-11-1627. [DOI] [PubMed] [Google Scholar]
  45. Lazar M. A., Hodin R. A., Darling D. S., Chin W. W. A novel member of the thyroid/steroid hormone receptor family is encoded by the opposite strand of the rat c-erbA alpha transcriptional unit. Mol Cell Biol. 1989 Mar;9(3):1128–1136. doi: 10.1128/mcb.9.3.1128. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Lazar M. A., Hodin R. A., Darling D. S., Chin W. W. Identification of a rat c-erbA alpha-related protein which binds deoxyribonucleic acid but does not bind thyroid hormone. Mol Endocrinol. 1988 Oct;2(10):893–901. doi: 10.1210/mend-2-10-893. [DOI] [PubMed] [Google Scholar]
  47. Leid M., Kastner P., Lyons R., Nakshatri H., Saunders M., Zacharewski T., Chen J. Y., Staub A., Garnier J. M., Mader S. Purification, cloning, and RXR identity of the HeLa cell factor with which RAR or TR heterodimerizes to bind target sequences efficiently. Cell. 1992 Jan 24;68(2):377–395. doi: 10.1016/0092-8674(92)90478-u. [DOI] [PubMed] [Google Scholar]
  48. Luisi B. F., Xu W. X., Otwinowski Z., Freedman L. P., Yamamoto K. R., Sigler P. B. Crystallographic analysis of the interaction of the glucocorticoid receptor with DNA. Nature. 1991 Aug 8;352(6335):497–505. doi: 10.1038/352497a0. [DOI] [PubMed] [Google Scholar]
  49. Marks M. S., Hallenbeck P. L., Nagata T., Segars J. H., Appella E., Nikodem V. M., Ozato K. H-2RIIBP (RXR beta) heterodimerization provides a mechanism for combinatorial diversity in the regulation of retinoic acid and thyroid hormone responsive genes. EMBO J. 1992 Apr;11(4):1419–1435. doi: 10.1002/j.1460-2075.1992.tb05187.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Murray M. B., Zilz N. D., McCreary N. L., MacDonald M. J., Towle H. C. Isolation and characterization of rat cDNA clones for two distinct thyroid hormone receptors. J Biol Chem. 1988 Sep 5;263(25):12770–12777. [PubMed] [Google Scholar]
  51. Muñoz A., Zenke M., Gehring U., Sap J., Beug H., Vennström B. Characterization of the hormone-binding domain of the chicken c-erbA/thyroid hormone receptor protein. EMBO J. 1988 Jan;7(1):155–159. doi: 10.1002/j.1460-2075.1988.tb02795.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Nagpal S., Friant S., Nakshatri H., Chambon P. RARs and RXRs: evidence for two autonomous transactivation functions (AF-1 and AF-2) and heterodimerization in vivo. EMBO J. 1993 Jun;12(6):2349–2360. doi: 10.1002/j.1460-2075.1993.tb05889.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Ornitz D. M., Moreadith R. W., Leder P. Binary system for regulating transgene expression in mice: targeting int-2 gene expression with yeast GAL4/UAS control elements. Proc Natl Acad Sci U S A. 1991 Feb 1;88(3):698–702. doi: 10.1073/pnas.88.3.698. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Park H. Y., Davidson D., Raaka B. M., Samuels H. H. The herpes simplex virus thymidine kinase gene promoter contains a novel thyroid hormone response element. Mol Endocrinol. 1993 Mar;7(3):319–330. doi: 10.1210/mend.7.3.8387156. [DOI] [PubMed] [Google Scholar]
  55. Perlman A. J., Stanley F., Samuels H. H. Thyroid hormone nuclear receptor. Evidence for multimeric organization in chromatin. J Biol Chem. 1982 Jan 25;257(2):930–938. [PubMed] [Google Scholar]
  56. Picard D., Salser S. J., Yamamoto K. R. A movable and regulable inactivation function within the steroid binding domain of the glucocorticoid receptor. Cell. 1988 Sep 23;54(7):1073–1080. doi: 10.1016/0092-8674(88)90122-5. [DOI] [PubMed] [Google Scholar]
  57. Ribeiro R. C., Kushner P. J., Apriletti J. W., West B. L., Baxter J. D. Thyroid hormone alters in vitro DNA binding of monomers and dimers of thyroid hormone receptors. Mol Endocrinol. 1992 Jul;6(7):1142–1152. doi: 10.1210/mend.6.7.1508227. [DOI] [PubMed] [Google Scholar]
  58. Roberts S. G., Ha I., Maldonado E., Reinberg D., Green M. R. Interaction between an acidic activator and transcription factor TFIIB is required for transcriptional activation. Nature. 1993 Jun 24;363(6431):741–744. doi: 10.1038/363741a0. [DOI] [PubMed] [Google Scholar]
  59. Saatcioglu F., Deng T., Karin M. A novel cis element mediating ligand-independent activation by c-ErbA: implications for hormonal regulation. Cell. 1993 Dec 17;75(6):1095–1105. doi: 10.1016/0092-8674(93)90319-l. [DOI] [PubMed] [Google Scholar]
  60. Sadowski I., Ma J., Triezenberg S., Ptashne M. GAL4-VP16 is an unusually potent transcriptional activator. Nature. 1988 Oct 6;335(6190):563–564. doi: 10.1038/335563a0. [DOI] [PubMed] [Google Scholar]
  61. Sadowski I., Ptashne M. A vector for expressing GAL4(1-147) fusions in mammalian cells. Nucleic Acids Res. 1989 Sep 25;17(18):7539–7539. doi: 10.1093/nar/17.18.7539. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Selmi S., Samuels H. H. Thyroid hormone receptor/and v-erbA. A single amino acid difference in the C-terminal region influences dominant negative activity and receptor dimer formation. J Biol Chem. 1991 Jun 25;266(18):11589–11593. [PubMed] [Google Scholar]
  63. Toney J. H., Wu L., Summerfield A. E., Sanyal G., Forman B. M., Zhu J., Samuels H. H. Conformational changes in chicken thyroid hormone receptor alpha 1 induced by binding to ligand or to DNA. Biochemistry. 1993 Jan 12;32(1):2–6. doi: 10.1021/bi00052a001. [DOI] [PubMed] [Google Scholar]
  64. Tran P., Zhang X. K., Salbert G., Hermann T., Lehmann J. M., Pfahl M. COUP orphan receptors are negative regulators of retinoic acid response pathways. Mol Cell Biol. 1992 Oct;12(10):4666–4676. doi: 10.1128/mcb.12.10.4666. [DOI] [PMC free article] [PubMed] [Google Scholar]
  65. Triezenberg S. J., Kingsbury R. C., McKnight S. L. Functional dissection of VP16, the trans-activator of herpes simplex virus immediate early gene expression. Genes Dev. 1988 Jun;2(6):718–729. doi: 10.1101/gad.2.6.718. [DOI] [PubMed] [Google Scholar]
  66. Wahlström G. M., Sjöberg M., Andersson M., Nordström K., Vennström B. Binding characteristics of the thyroid hormone receptor homo- and heterodimers to consensus AGGTCA repeat motifs. Mol Endocrinol. 1992 Jul;6(7):1013–1022. doi: 10.1210/mend.6.7.1324417. [DOI] [PubMed] [Google Scholar]
  67. Wang L. H., Tsai S. Y., Cook R. G., Beattie W. G., Tsai M. J., O'Malley B. W. COUP transcription factor is a member of the steroid receptor superfamily. Nature. 1989 Jul 13;340(6229):163–166. doi: 10.1038/340163a0. [DOI] [PubMed] [Google Scholar]
  68. Weinberger C., Thompson C. C., Ong E. S., Lebo R., Gruol D. J., Evans R. M. The c-erb-A gene encodes a thyroid hormone receptor. Nature. 1986 Dec 18;324(6098):641–646. doi: 10.1038/324641a0. [DOI] [PubMed] [Google Scholar]
  69. Wiech H., Buchner J., Zimmermann R., Jakob U. Hsp90 chaperones protein folding in vitro. Nature. 1992 Jul 9;358(6382):169–170. doi: 10.1038/358169a0. [DOI] [PubMed] [Google Scholar]
  70. Yen P. M., Darling D. S., Carter R. L., Forgione M., Umeda P. K., Chin W. W. Triiodothyronine (T3) decreases binding to DNA by T3-receptor homodimers but not receptor-auxiliary protein heterodimers. J Biol Chem. 1992 Feb 25;267(6):3565–3568. [PubMed] [Google Scholar]
  71. Yen P. M., Sugawara A., Chin W. W. Triiodothyronine (T3) differentially affects T3-receptor/retinoic acid receptor and T3-receptor/retinoid X receptor heterodimer binding to DNA. J Biol Chem. 1992 Nov 15;267(32):23248–23252. [PubMed] [Google Scholar]
  72. Yu V. C., Delsert C., Andersen B., Holloway J. M., Devary O. V., När A. M., Kim S. Y., Boutin J. M., Glass C. K., Rosenfeld M. G. RXR beta: a coregulator that enhances binding of retinoic acid, thyroid hormone, and vitamin D receptors to their cognate response elements. Cell. 1991 Dec 20;67(6):1251–1266. doi: 10.1016/0092-8674(91)90301-e. [DOI] [PubMed] [Google Scholar]
  73. Zhang X. K., Hoffmann B., Tran P. B., Graupner G., Pfahl M. Retinoid X receptor is an auxiliary protein for thyroid hormone and retinoic acid receptors. Nature. 1992 Jan 30;355(6359):441–446. doi: 10.1038/355441a0. [DOI] [PubMed] [Google Scholar]
  74. Zhang X. K., Lehmann J., Hoffmann B., Dawson M. I., Cameron J., Graupner G., Hermann T., Tran P., Pfahl M. Homodimer formation of retinoid X receptor induced by 9-cis retinoic acid. Nature. 1992 Aug 13;358(6387):587–591. doi: 10.1038/358587a0. [DOI] [PubMed] [Google Scholar]

Articles from Molecular and Cellular Biology are provided here courtesy of Taylor & Francis

RESOURCES