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. 1996 Aug;16(8):4137–4146. doi: 10.1128/mcb.16.8.4137

The receptor-DNA complex determines the retinoid response: a mechanism for the diversification of the ligand signal.

N La Vista-Picard 1, P D Hobbs 1, M Pfahl 1, M I Dawson 1, M Pfahl 1
PMCID: PMC231410  PMID: 8754812

Abstract

To obtain insights into the principles governing the complex biological responses to retinoids, we have analyzed the ligand sensitivities of various retinoid receptor-DNA complexes. We find that different retinoid receptor heterodimers show distinct activation patterns with various response elements while a given heterodimer can be activated at different retinoic acid concentrations on different response elements. In vitro binding experiments suggest that the same retinoic acid receptor-retinoid X receptor (RAR-RXR) heterodimer can have different ligand affinities, depending on the response element it is bound to. The differential responses of a particular receptor heterodimer with various retinoic acid responsive elements can be enhanced through the use of conformationally restricted retinoids. RAR- and RXR-selective retinoids can also synergistically activate the receptor heterodimers, indicating that both partners in the heterodimer can contribute to ligand-induced transcriptional activation. However, the relative influence of the RAR or RXR partner is specific for each response element. Together, our data demonstrate that it is the receptor-DNA complex and not the receptor alone that determines the ligand response. This flexibility allows for a highly pleiotropic retinoid response. Furthermore, conformationally restricted retinoids can accentuate the differential responses and exhibit a certain degree of gene selectivity by differentially activating the RAR or RXR component in the context of a given response element.

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Selected References

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  1. Allenby G., Bocquel M. T., Saunders M., Kazmer S., Speck J., Rosenberger M., Lovey A., Kastner P., Grippo J. F., Chambon P. Retinoic acid receptors and retinoid X receptors: interactions with endogenous retinoic acids. Proc Natl Acad Sci U S A. 1993 Jan 1;90(1):30–34. doi: 10.1073/pnas.90.1.30. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Apfel R., Benbrook D., Lernhardt E., Ortiz M. A., Salbert G., Pfahl M. A novel orphan receptor specific for a subset of thyroid hormone-responsive elements and its interaction with the retinoid/thyroid hormone receptor subfamily. Mol Cell Biol. 1994 Oct;14(10):7025–7035. doi: 10.1128/mcb.14.10.7025. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Baes M., Gulick T., Choi H. S., Martinoli M. G., Simha D., Moore D. D. A new orphan member of the nuclear hormone receptor superfamily that interacts with a subset of retinoic acid response elements. Mol Cell Biol. 1994 Mar;14(3):1544–1552. doi: 10.1128/mcb.14.3.1544. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Beato M. Gene regulation by steroid hormones. Cell. 1989 Feb 10;56(3):335–344. doi: 10.1016/0092-8674(89)90237-7. [DOI] [PubMed] [Google Scholar]
  5. Benbrook D., Lernhardt E., Pfahl M. A new retinoic acid receptor identified from a hepatocellular carcinoma. Nature. 1988 Jun 16;333(6174):669–672. doi: 10.1038/333669a0. [DOI] [PubMed] [Google Scholar]
  6. Bernard B. A., Bernardon J. M., Delescluse C., Martin B., Lenoir M. C., Maignan J., Charpentier B., Pilgrim W. R., Reichert U., Shroot B. Identification of synthetic retinoids with selectivity for human nuclear retinoic acid receptor gamma. Biochem Biophys Res Commun. 1992 Jul 31;186(2):977–983. doi: 10.1016/0006-291x(92)90842-9. [DOI] [PubMed] [Google Scholar]
  7. Boehm M. F., Zhang L., Badea B. A., White S. K., Mais D. E., Berger E., Suto C. M., Goldman M. E., Heyman R. A. Synthesis and structure-activity relationships of novel retinoid X receptor-selective retinoids. J Med Chem. 1994 Sep 2;37(18):2930–2941. doi: 10.1021/jm00044a014. [DOI] [PubMed] [Google Scholar]
  8. Bollag W., Holdener E. E. Retinoids in cancer prevention and therapy. Ann Oncol. 1992 Jul;3(7):513–526. doi: 10.1093/oxfordjournals.annonc.a058252. [DOI] [PubMed] [Google Scholar]
  9. Bollag W. Vitamin A and retinoids: from nutrition to pharmacotherapy in dermatology and oncology. Lancet. 1983 Apr 16;1(8329):860–863. doi: 10.1016/s0140-6736(83)91394-6. [DOI] [PubMed] [Google Scholar]
  10. Brand N., Petkovich M., Krust A., Chambon P., de Thé H., Marchio A., Tiollais P., Dejean A. Identification of a second human retinoic acid receptor. Nature. 1988 Apr 28;332(6167):850–853. doi: 10.1038/332850a0. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. Castaigne S., Chomienne C., Daniel M. T., Ballerini P., Berger R., Fenaux P., Degos L. All-trans retinoic acid as a differentiation therapy for acute promyelocytic leukemia. I. Clinical results. Blood. 1990 Nov 1;76(9):1704–1709. [PubMed] [Google Scholar]
  13. Chambon P. The retinoid signaling pathway: molecular and genetic analyses. Semin Cell Biol. 1994 Apr;5(2):115–125. doi: 10.1006/scel.1994.1015. [DOI] [PubMed] [Google Scholar]
  14. Delescluse C., Cavey M. T., Martin B., Bernard B. A., Reichert U., Maignan J., Darmon M., Shroot B. Selective high affinity retinoic acid receptor alpha or beta-gamma ligands. Mol Pharmacol. 1991 Oct;40(4):556–562. [PubMed] [Google Scholar]
  15. Edwards M. K., McBurney M. W. The concentration of retinoic acid determines the differentiated cell types formed by a teratocarcinoma cell line. Dev Biol. 1983 Jul;98(1):187–191. doi: 10.1016/0012-1606(83)90348-2. [DOI] [PubMed] [Google Scholar]
  16. Ellis L., Clauser E., Morgan D. O., Edery M., Roth R. A., Rutter W. J. Replacement of insulin receptor tyrosine residues 1162 and 1163 compromises insulin-stimulated kinase activity and uptake of 2-deoxyglucose. Cell. 1986 Jun 6;45(5):721–732. doi: 10.1016/0092-8674(86)90786-5. [DOI] [PubMed] [Google Scholar]
  17. Fanjul A., Dawson M. I., Hobbs P. D., Jong L., Cameron J. F., Harlev E., Graupner G., Lu X. P., Pfahl M. A new class of retinoids with selective inhibition of AP-1 inhibits proliferation. Nature. 1994 Nov 3;372(6501):107–111. doi: 10.1038/372107a0. [DOI] [PubMed] [Google Scholar]
  18. Giguere V., Ong E. S., Segui P., Evans R. M. Identification of a receptor for the morphogen retinoic acid. Nature. 1987 Dec 17;330(6149):624–629. doi: 10.1038/330624a0. [DOI] [PubMed] [Google Scholar]
  19. Glass C. K., DiRenzo J., Kurokawa R., Han Z. H. Regulation of gene expression by retinoic acid receptors. DNA Cell Biol. 1991 Nov;10(9):623–638. doi: 10.1089/dna.1991.10.623. [DOI] [PubMed] [Google Scholar]
  20. Goodman D. S. Vitamin A and retinoids in health and disease. N Engl J Med. 1984 Apr 19;310(16):1023–1031. doi: 10.1056/NEJM198404193101605. [DOI] [PubMed] [Google Scholar]
  21. Graupner G., Malle G., Maignan J., Lang G., Pruniéras M., Pfahl M. 6'-substituted naphthalene-2-carboxylic acid analogs, a new class of retinoic acid receptor subtype-specific ligands. Biochem Biophys Res Commun. 1991 Sep 30;179(3):1554–1561. doi: 10.1016/0006-291x(91)91750-7. [DOI] [PubMed] [Google Scholar]
  22. Hermann T., Hoffmann B., Zhang X. K., Tran P., Pfahl M. Heterodimeric receptor complexes determine 3,5,3'-triiodothyronine and retinoid signaling specificities. Mol Endocrinol. 1992 Jul;6(7):1153–1162. doi: 10.1210/mend.6.7.1324421. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. Hill D. L., Grubbs C. J. Retinoids and cancer prevention. Annu Rev Nutr. 1992;12:161–181. doi: 10.1146/annurev.nu.12.070192.001113. [DOI] [PubMed] [Google Scholar]
  25. Hong W. K., Lippman S. M., Itri L. M., Karp D. D., Lee J. S., Byers R. M., Schantz S. P., Kramer A. M., Lotan R., Peters L. J. Prevention of second primary tumors with isotretinoin in squamous-cell carcinoma of the head and neck. N Engl J Med. 1990 Sep 20;323(12):795–801. doi: 10.1056/NEJM199009203231205. [DOI] [PubMed] [Google Scholar]
  26. Huang M. E., Ye Y. C., Chen S. R., Chai J. R., Lu J. X., Zhoa L., Gu L. J., Wang Z. Y. Use of all-trans retinoic acid in the treatment of acute promyelocytic leukemia. Blood. 1988 Aug;72(2):567–572. [PubMed] [Google Scholar]
  27. Husmann M., Hoffmann B., Stump D. G., Chytil F., Pfahl M. A retinoic acid response element from the rat CRBPI promoter is activated by an RAR/RXR heterodimer. Biochem Biophys Res Commun. 1992 Sep 30;187(3):1558–1564. doi: 10.1016/0006-291x(92)90480-9. [DOI] [PubMed] [Google Scholar]
  28. Husmann M., Lehmann J., Hoffmann B., Hermann T., Tzukerman M., Pfahl M. Antagonism between retinoic acid receptors. Mol Cell Biol. 1991 Aug;11(8):4097–4103. doi: 10.1128/mcb.11.8.4097. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. 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]
  30. Kliewer S. A., Umesono K., Noonan D. J., Heyman R. A., Evans R. M. Convergence of 9-cis retinoic acid and peroxisome proliferator signalling pathways through heterodimer formation of their receptors. Nature. 1992 Aug 27;358(6389):771–774. doi: 10.1038/358771a0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Kraemer K. H., DiGiovanna J. J., Moshell A. N., Tarone R. E., Peck G. L. Prevention of skin cancer in xeroderma pigmentosum with the use of oral isotretinoin. N Engl J Med. 1988 Jun 23;318(25):1633–1637. doi: 10.1056/NEJM198806233182501. [DOI] [PubMed] [Google Scholar]
  32. Kraemer K. H., DiGiovanna J. J., Peck G. L. Chemoprevention of skin cancer in xeroderma pigmentosum. J Dermatol. 1992 Nov;19(11):715–718. doi: 10.1111/j.1346-8138.1992.tb03766.x. [DOI] [PubMed] [Google Scholar]
  33. Kurokawa R., DiRenzo J., Boehm M., Sugarman J., Gloss B., Rosenfeld M. G., Heyman R. A., Glass C. K. Regulation of retinoid signalling by receptor polarity and allosteric control of ligand binding. Nature. 1994 Oct 6;371(6497):528–531. doi: 10.1038/371528a0. [DOI] [PubMed] [Google Scholar]
  34. Kurokawa R., Söderström M., Hörlein A., Halachmi S., Brown M., Rosenfeld M. G., Glass C. K. Polarity-specific activities of retinoic acid receptors determined by a co-repressor. Nature. 1995 Oct 5;377(6548):451–454. doi: 10.1038/377451a0. [DOI] [PubMed] [Google Scholar]
  35. Kurokawa R., Yu V. C., När A., Kyakumoto S., Han Z., Silverman S., Rosenfeld M. G., Glass C. K. Differential orientations of the DNA-binding domain and carboxy-terminal dimerization interface regulate binding site selection by nuclear receptor heterodimers. Genes Dev. 1993 Jul;7(7B):1423–1435. doi: 10.1101/gad.7.7b.1423. [DOI] [PubMed] [Google Scholar]
  36. Lee M. O., Hobbs P. D., Zhang X. K., Dawson M. I., Pfahl M. A synthetic retinoid antagonist inhibits the human immunodeficiency virus type 1 promoter. Proc Natl Acad Sci U S A. 1994 Jun 7;91(12):5632–5636. doi: 10.1073/pnas.91.12.5632. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Lehmann J. M., Dawson M. I., Hobbs P. D., Husmann M., Pfahl M. Identification of retinoids with nuclear receptor subtype-selective activities. Cancer Res. 1991 Sep 15;51(18):4804–4809. [PubMed] [Google Scholar]
  38. Lehmann J. M., Jong L., Fanjul A., Cameron J. F., Lu X. P., Haefner P., Dawson M. I., Pfahl M. Retinoids selective for retinoid X receptor response pathways. Science. 1992 Dec 18;258(5090):1944–1946. doi: 10.1126/science.1335166. [DOI] [PubMed] [Google Scholar]
  39. Lehmann J. M., Zhang X. K., Graupner G., Lee M. O., Hermann T., Hoffmann B., Pfahl M. Formation of retinoid X receptor homodimers leads to repression of T3 response: hormonal cross talk by ligand-induced squelching. Mol Cell Biol. 1993 Dec;13(12):7698–7707. doi: 10.1128/mcb.13.12.7698. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Lehmann J. M., Zhang X. K., Pfahl M. RAR gamma 2 expression is regulated through a retinoic acid response element embedded in Sp1 sites. Mol Cell Biol. 1992 Jul;12(7):2976–2985. doi: 10.1128/mcb.12.7.2976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Leid M., Kastner P., Chambon P. Multiplicity generates diversity in the retinoic acid signalling pathways. Trends Biochem Sci. 1992 Oct;17(10):427–433. doi: 10.1016/0968-0004(92)90014-z. [DOI] [PubMed] [Google Scholar]
  42. 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]
  43. Lippman S. M., Kessler J. F., Meyskens F. L., Jr Retinoids as preventive and therapeutic anticancer agents (Part II). Cancer Treat Rep. 1987 May;71(5):493–515. [PubMed] [Google Scholar]
  44. Lombardo A., Costa E., Chao W. R., Toll L., Hobbs P. D., Jong L., Lee M. O., Pfahl M., Ely K. R., Dawson M. I. Recombinant human retinoic acid receptor beta. Binding of synthetic retinoids and transcriptional activation. J Biol Chem. 1994 Mar 11;269(10):7297–7303. [PubMed] [Google Scholar]
  45. Lotan R. Effects of vitamin A and its analogs (retinoids) on normal and neoplastic cells. Biochim Biophys Acta. 1980 Mar 12;605(1):33–91. doi: 10.1016/0304-419x(80)90021-9. [DOI] [PubMed] [Google Scholar]
  46. Lu X. P., Eberhardt N. L., Pfahl M. DNA bending by retinoid X receptor-containing retinoid and thyroid hormone receptor complexes. Mol Cell Biol. 1993 Oct;13(10):6509–6519. doi: 10.1128/mcb.13.10.6509. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Mader S., Chen J. Y., Chen Z., White J., Chambon P., Gronemeyer H. The patterns of binding of RAR, RXR and TR homo- and heterodimers to direct repeats are dictated by the binding specificites of the DNA binding domains. EMBO J. 1993 Dec 15;12(13):5029–5041. doi: 10.1002/j.1460-2075.1993.tb06196.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. 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]
  49. 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]
  50. 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]
  51. 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]
  52. Nagpal S., Saunders M., Kastner P., Durand B., Nakshatri H., Chambon P. Promoter context- and response element-dependent specificity of the transcriptional activation and modulating functions of retinoic acid receptors. Cell. 1992 Sep 18;70(6):1007–1019. doi: 10.1016/0092-8674(92)90250-g. [DOI] [PubMed] [Google Scholar]
  53. Petkovich M., Brand N. J., Krust A., Chambon P. A human retinoic acid receptor which belongs to the family of nuclear receptors. Nature. 1987 Dec 3;330(6147):444–450. doi: 10.1038/330444a0. [DOI] [PubMed] [Google Scholar]
  54. Pfahl M., Apfel R., Bendik I., Fanjul A., Graupner G., Lee M. O., La-Vista N., Lu X. P., Piedrafita J., Ortiz M. A. Nuclear retinoid receptors and their mechanism of action. Vitam Horm. 1994;49:327–382. doi: 10.1016/s0083-6729(08)61150-4. [DOI] [PubMed] [Google Scholar]
  55. Pfahl M. Nuclear receptor/AP-1 interaction. Endocr Rev. 1993 Oct;14(5):651–658. doi: 10.1210/edrv-14-5-651. [DOI] [PubMed] [Google Scholar]
  56. Pijnappel W. W., Hendriks H. F., Folkers G. E., van den Brink C. E., Dekker E. J., Edelenbosch C., van der Saag P. T., Durston A. J. The retinoid ligand 4-oxo-retinoic acid is a highly active modulator of positional specification. Nature. 1993 Nov 25;366(6453):340–344. doi: 10.1038/366340a0. [DOI] [PubMed] [Google Scholar]
  57. Predki P. F., Zamble D., Sarkar B., Giguère V. Ordered binding of retinoic acid and retinoid-X receptors to asymmetric response elements involves determinants adjacent to the DNA-binding domain. Mol Endocrinol. 1994 Jan;8(1):31–39. doi: 10.1210/mend.8.1.8152429. [DOI] [PubMed] [Google Scholar]
  58. Rottman J. N., Widom R. L., Nadal-Ginard B., Mahdavi V., Karathanasis S. K. A retinoic acid-responsive element in the apolipoprotein AI gene distinguishes between two different retinoic acid response pathways. Mol Cell Biol. 1991 Jul;11(7):3814–3820. doi: 10.1128/mcb.11.7.3814. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Salbert G., Fanjul A., Piedrafita F. J., Lu X. P., Kim S. J., Tran P., Pfahl M. Retinoic acid receptors and retinoid X receptor-alpha down-regulate the transforming growth factor-beta 1 promoter by antagonizing AP-1 activity. Mol Endocrinol. 1993 Oct;7(10):1347–1356. doi: 10.1210/mend.7.10.8264664. [DOI] [PubMed] [Google Scholar]
  60. Schüle R., Rangarajan P., Yang N., Kliewer S., Ransone L. J., Bolado J., Verma I. M., Evans R. M. Retinoic acid is a negative regulator of AP-1-responsive genes. Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):6092–6096. doi: 10.1073/pnas.88.14.6092. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Smith M. A., Parkinson D. R., Cheson B. D., Friedman M. A. Retinoids in cancer therapy. J Clin Oncol. 1992 May;10(5):839–864. doi: 10.1200/JCO.1992.10.5.839. [DOI] [PubMed] [Google Scholar]
  62. 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]
  63. Thaller C., Eichele G. Isolation of 3,4-didehydroretinoic acid, a novel morphogenetic signal in the chick wing bud. Nature. 1990 Jun 28;345(6278):815–819. doi: 10.1038/345815a0. [DOI] [PubMed] [Google Scholar]
  64. Tini M., Otulakowski G., Breitman M. L., Tsui L. C., Giguère V. An everted repeat mediates retinoic acid induction of the gamma F-crystallin gene: evidence of a direct role for retinoids in lens development. Genes Dev. 1993 Feb;7(2):295–307. doi: 10.1101/gad.7.2.295. [DOI] [PubMed] [Google Scholar]
  65. 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]
  66. Yang-Yen H. F., Zhang X. K., Graupner G., Tzukerman M., Sakamoto B., Karin M., Pfahl M. Antagonism between retinoic acid receptors and AP-1: implications for tumor promotion and inflammation. New Biol. 1991 Dec;3(12):1206–1219. [PubMed] [Google Scholar]
  67. 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]
  68. Zechel C., Shen X. Q., Chen J. Y., Chen Z. P., Chambon P., Gronemeyer H. The dimerization interfaces formed between the DNA binding domains of RXR, RAR and TR determine the binding specificity and polarity of the full-length receptors to direct repeats. EMBO J. 1994 Mar 15;13(6):1425–1433. doi: 10.1002/j.1460-2075.1994.tb06396.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  69. 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]
  70. 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]
  71. de Thé H., Vivanco-Ruiz M. M., Tiollais P., Stunnenberg H., Dejean A. Identification of a retinoic acid responsive element in the retinoic acid receptor beta gene. Nature. 1990 Jan 11;343(6254):177–180. doi: 10.1038/343177a0. [DOI] [PubMed] [Google Scholar]

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