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. 1993 Sep;13(9):5725–5737. doi: 10.1128/mcb.13.9.5725

The conserved ninth C-terminal heptad in thyroid hormone and retinoic acid receptors mediates diverse responses by affecting heterodimer but not homodimer formation.

M Au-Fliegner 1, E Helmer 1, J Casanova 1, B M Raaka 1, H H Samuels 1
PMCID: PMC360309  PMID: 8395010

Abstract

The receptors for thyroid hormone (T3R), all-trans-retinoic acid (RAR), and 9-cis-retinoic acid (RXR) bind DNA response elements as homo- and heterodimers. The ligand-binding domains of these receptors contain nine conserved heptads proposed to play a role in dimerization. Mutant receptors with changes in the first or last hydrophobic amino acids in the highly conserved ninth heptad of chick T3R alpha [cT3R alpha(L365R) and cT3R(L372R)] and human RAR alpha (hRAR alpha) [hRAR(M377R) and hRAR(L384R)] reveal that this heptad is essential for certain heterodimeric interactions and for diverse functional activities. Without ligands, wild-type receptors form both homodimers and heterodimers, while these mutants form only homodimers. Surprisingly, the cognate ligand for each mutant enables heterodimer formation between cT3R(L365R) and RAR or RXR and between hRAR(M377R) and T3R or RXR. Both cT3R(L365R) and hRAR(M377R) mediate ligand-dependent transcriptional regulation. However, unlike the wild-type receptor, non-ligand-associated cT3R(L365R) does not suppress the basal activity of certain promoters containing thyroid hormone response elements, suggesting that this silencing effect of T3R is mediated by unliganded heterodimers of T3R and endogenous RXR or related factors. Heterodimerization is also necessary for the strong ligand-independent inhibition between T3R and RAR on a common response element, since the ninth-heptad mutants function as poor inhibitors. However, with a T3R-specific response element, hRAR(M377R) acts as a retinoic acid-dependent inhibitor of cT3R, indicating the importance of heterodimerization for this inhibition. Our studies also suggest that the ninth heptad is necessary for the dominant inhibition of wild-type T3Rs by mutant T3Rs, as has been found for the thyroid hormone-resistant syndrome in humans. Thus, the ninth heptad repeat is required for heterodimerization, suppression of basal promoter activity, and dominant negative effects of T3R and RAR. Lastly, the finding that cT3R(L365R) and hRAR(M377R) require ligands for heterodimer formation also raises the possibility that heterodimeric interactions are mediated by the ninth heptad without ligands but by a second region of these receptors with ligands.

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Selected References

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

  1. 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]
  2. 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]
  3. 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]
  4. 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]
  5. Brent G. A., Harney J. W., Chen Y., Warne R. L., Moore D. D., Larsen P. R. Mutations of the rat growth hormone promoter which increase and decrease response to thyroid hormone define a consensus thyroid hormone response element. Mol Endocrinol. 1989 Dec;3(12):1996–2004. doi: 10.1210/mend-3-12-1996. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Burnside J., Darling D. S., Chin W. W. A nuclear factor that enhances binding of thyroid hormone receptors to thyroid hormone response elements. J Biol Chem. 1990 Feb 15;265(5):2500–2504. [PubMed] [Google Scholar]
  8. 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]
  9. Chatterjee V. K., Nagaya T., Madison L. D., Datta S., Rentoumis A., Jameson J. L. Thyroid hormone resistance syndrome. Inhibition of normal receptor function by mutant thyroid hormone receptors. J Clin Invest. 1991 Jun;87(6):1977–1984. doi: 10.1172/JCI115225. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. 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]
  11. 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]
  12. Darling D. S., Beebe J. S., Burnside J., Winslow E. R., Chin W. W. 3,5,3'-triiodothyronine (T3) receptor-auxiliary protein (TRAP) binds DNA and forms heterodimers with the T3 receptor. Mol Endocrinol. 1991 Jan;5(1):73–84. doi: 10.1210/mend-5-1-73. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. 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]
  15. 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]
  16. 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]
  17. 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]
  18. 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]
  19. Gorman C. M., Moffat L. F., Howard B. H. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol Cell Biol. 1982 Sep;2(9):1044–1051. doi: 10.1128/mcb.2.9.1044. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Graupner G., Wills K. N., Tzukerman M., Zhang X. K., Pfahl M. Dual regulatory role for thyroid-hormone receptors allows control of retinoic-acid receptor activity. Nature. 1989 Aug 24;340(6235):653–656. doi: 10.1038/340653a0. [DOI] [PubMed] [Google Scholar]
  21. 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]
  22. Heyman R. A., Mangelsdorf D. J., Dyck J. A., Stein R. B., Eichele G., Evans R. M., Thaller C. 9-cis retinoic acid is a high affinity ligand for the retinoid X receptor. Cell. 1992 Jan 24;68(2):397–406. doi: 10.1016/0092-8674(92)90479-v. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. 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]
  25. Katz D., Berrodin T. J., Lazar M. A. The unique C-termini of the thyroid hormone receptor variant, c-erbA alpha 2, and thyroid hormone receptor alpha 1 mediate different DNA-binding and heterodimerization properties. Mol Endocrinol. 1992 May;6(5):805–814. doi: 10.1210/mend.6.5.1318505. [DOI] [PubMed] [Google Scholar]
  26. 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]
  27. Koenig R. J., Lazar M. A., Hodin R. A., Brent G. A., Larsen P. R., Chin W. W., Moore D. D. Inhibition of thyroid hormone action by a non-hormone binding c-erbA protein generated by alternative mRNA splicing. Nature. 1989 Feb 16;337(6208):659–661. doi: 10.1038/337659a0. [DOI] [PubMed] [Google Scholar]
  28. 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]
  29. 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]
  30. Lazar M. A., Jones K. E., Chin W. W. Isolation of a cDNA encoding human Rev-ErbA alpha: transcription from the noncoding DNA strand of a thyroid hormone receptor gene results in a related protein that does not bind thyroid hormone. DNA Cell Biol. 1990 Mar;9(2):77–83. doi: 10.1089/dna.1990.9.77. [DOI] [PubMed] [Google Scholar]
  31. Lee J. W., Gulick T., Moore D. D. Thyroid hormone receptor dimerization function maps to a conserved subregion of the ligand binding domain. Mol Endocrinol. 1992 Nov;6(11):1867–1873. doi: 10.1210/mend.6.11.1480176. [DOI] [PubMed] [Google Scholar]
  32. 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]
  33. Levin A. A., Sturzenbecker L. J., Kazmer S., Bosakowski T., Huselton C., Allenby G., Speck J., Kratzeisen C., Rosenberger M., Lovey A. 9-cis retinoic acid stereoisomer binds and activates the nuclear receptor RXR alpha. Nature. 1992 Jan 23;355(6358):359–361. doi: 10.1038/355359a0. [DOI] [PubMed] [Google Scholar]
  34. Lucas P. C., Forman B. M., Samuels H. H., Granner D. K. Specificity of a retinoic acid response element in the phosphoenolpyruvate carboxykinase gene promoter: consequences of both retinoic acid and thyroid hormone receptor binding. Mol Cell Biol. 1991 Oct;11(10):5164–5170. doi: 10.1128/mcb.11.10.5164. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Luckow B., Schütz G. CAT constructions with multiple unique restriction sites for the functional analysis of eukaryotic promoters and regulatory elements. Nucleic Acids Res. 1987 Jul 10;15(13):5490–5490. doi: 10.1093/nar/15.13.5490. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. 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]
  37. Mangelsdorf D. J., Borgmeyer U., Heyman R. A., Zhou J. Y., Ong E. S., Oro A. E., Kakizuka A., Evans R. M. Characterization of three RXR genes that mediate the action of 9-cis retinoic acid. Genes Dev. 1992 Mar;6(3):329–344. doi: 10.1101/gad.6.3.329. [DOI] [PubMed] [Google Scholar]
  38. Mangelsdorf D. J., Umesono K., Kliewer S. A., Borgmeyer U., Ong E. S., Evans R. M. A direct repeat in the cellular retinol-binding protein type II gene confers differential regulation by RXR and RAR. Cell. 1991 Aug 9;66(3):555–561. doi: 10.1016/0092-8674(81)90018-0. [DOI] [PubMed] [Google Scholar]
  39. 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]
  40. Marks M. S., Levi B. Z., Segars J. H., Driggers P. H., Hirschfeld S., Nagata T., Appella E., Ozato K. H-2RIIBP expressed from a baculovirus vector binds to multiple hormone response elements. Mol Endocrinol. 1992 Feb;6(2):219–230. doi: 10.1210/mend.6.2.1569965. [DOI] [PubMed] [Google Scholar]
  41. Miyamoto T., Suzuki S., DeGroot L. J. High affinity and specificity of dimeric binding of thyroid hormone receptors to DNA and their ligand-dependent dissociation. Mol Endocrinol. 1993 Feb;7(2):224–231. doi: 10.1210/mend.7.2.8469235. [DOI] [PubMed] [Google Scholar]
  42. Murray M. B., Towle H. C. Identification of nuclear factors that enhance binding of the thyroid hormone receptor to a thyroid hormone response element. Mol Endocrinol. 1989 Sep;3(9):1434–1442. doi: 10.1210/mend-3-9-1434. [DOI] [PubMed] [Google Scholar]
  43. När A. M., Boutin J. M., Lipkin S. M., Yu V. C., Holloway J. M., Glass C. K., Rosenfeld M. G. The orientation and spacing of core DNA-binding motifs dictate selective transcriptional responses to three nuclear receptors. Cell. 1991 Jun 28;65(7):1267–1279. doi: 10.1016/0092-8674(91)90021-p. [DOI] [PubMed] [Google Scholar]
  44. O'Donnell A. L., Koenig R. J. Mutational analysis identifies a new functional domain of the thyroid hormone receptor. Mol Endocrinol. 1990 May;4(5):715–720. doi: 10.1210/mend-4-5-715. [DOI] [PubMed] [Google Scholar]
  45. O'Donnell A. L., Rosen E. D., Darling D. S., Koenig R. J. Thyroid hormone receptor mutations that interfere with transcriptional activation also interfere with receptor interaction with a nuclear protein. Mol Endocrinol. 1991 Jan;5(1):94–99. doi: 10.1210/mend-5-1-94. [DOI] [PubMed] [Google Scholar]
  46. 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]
  47. Refetoff S., DeGroot L. J., Benard B., DeWind L. T. Studies of a sibship with apparent hereditary resistance to the intracellular action of thyroid hormone. Metabolism. 1972 Aug;21(8):723–756. doi: 10.1016/0026-0495(72)90121-7. [DOI] [PubMed] [Google Scholar]
  48. 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]
  49. Sakurai A., Miyamoto T., Refetoff S., DeGroot L. J. Dominant negative transcriptional regulation by a mutant thyroid hormone receptor-beta in a family with generalized resistance to thyroid hormone. Mol Endocrinol. 1990 Dec;4(12):1988–1994. doi: 10.1210/mend-4-12-1988. [DOI] [PubMed] [Google Scholar]
  50. Sakurai A., Takeda K., Ain K., Ceccarelli P., Nakai A., Seino S., Bell G. I., Refetoff S., DeGroot L. J. Generalized resistance to thyroid hormone associated with a mutation in the ligand-binding domain of the human thyroid hormone receptor beta. Proc Natl Acad Sci U S A. 1989 Nov;86(22):8977–8981. doi: 10.1073/pnas.86.22.8977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. 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]
  52. Sucov H. M., Murakami K. K., Evans R. M. Characterization of an autoregulated response element in the mouse retinoic acid receptor type beta gene. Proc Natl Acad Sci U S A. 1990 Jul;87(14):5392–5396. doi: 10.1073/pnas.87.14.5392. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Tomic M., Jiang C. K., Epstein H. S., Freedberg I. M., Samuels H. H., Blumenberg M. Nuclear receptors for retinoic acid and thyroid hormone regulate transcription of keratin genes. Cell Regul. 1990 Nov;1(12):965–973. doi: 10.1091/mbc.1.12.965. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. 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]
  55. Umesono K., Giguere V., Glass C. K., Rosenfeld M. G., Evans R. M. Retinoic acid and thyroid hormone induce gene expression through a common responsive element. Nature. 1988 Nov 17;336(6196):262–265. doi: 10.1038/336262a0. [DOI] [PubMed] [Google Scholar]
  56. Umesono K., Murakami K. K., Thompson C. C., Evans R. M. Direct repeats as selective response elements for the thyroid hormone, retinoic acid, and vitamin D3 receptors. Cell. 1991 Jun 28;65(7):1255–1266. doi: 10.1016/0092-8674(91)90020-y. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Usala S. J., Bale A. E., Gesundheit N., Weinberger C., Lash R. W., Wondisford F. E., McBride O. W., Weintraub B. D. Tight linkage between the syndrome of generalized thyroid hormone resistance and the human c-erbA beta gene. Mol Endocrinol. 1988 Dec;2(12):1217–1220. doi: 10.1210/mend-2-12-1217. [DOI] [PubMed] [Google Scholar]
  58. Usala S. J., Menke J. B., Watson T. L., Wondisford F. E., Weintraub B. D., Bérard J., Bradley W. E., Ono S., Mueller O. T., Bercu B. B. A homozygous deletion in the c-erbA beta thyroid hormone receptor gene in a patient with generalized thyroid hormone resistance: isolation and characterization of the mutant receptor. Mol Endocrinol. 1991 Mar;5(3):327–335. doi: 10.1210/mend-5-3-327. [DOI] [PubMed] [Google Scholar]
  59. Usala S. J. Molecular diagnosis and characterization of thyroid hormone resistance syndromes. Thyroid. 1991 Winter;1(4):361–367. doi: 10.1089/thy.1991.1.361. [DOI] [PubMed] [Google Scholar]
  60. 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]
  61. Ye Z. S., Forman B. M., Aranda A., Pascual A., Park H. Y., Casanova J., Samuels H. H. Rat growth hormone gene expression. Both cell-specific and thyroid hormone response elements are required for thyroid hormone regulation. J Biol Chem. 1988 Jun 5;263(16):7821–7829. [PubMed] [Google Scholar]
  62. 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]
  63. 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]
  64. 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]
  65. 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]

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