Journal of Endocrinology and Reproduction

Open Access Open Access  Restricted Access Subscription Access
Open Access Open Access Open Access  Restricted Access Restricted Access Subscription Access

A Compendium of Nuclear Receptors:The Superfamily of Ligand-Modulated Transcription Factors


Affiliations
1 Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi – 110067, India
     

   Subscribe/Renew Journal


The ‘Nuclear Receptor Super-family’ is a group of ligand-modulated transcription factors with 48 members identified in human genome. Members of this family of receptors are now established to be involved in regulation of a plethora of physiological processes in the paradigms of development, reproduction, metabolism and homeostasis. Also, in the myriads of patho-physiological processes, these receptors have consistently exhibited enormous potential as targets for the treatment of diseases such as cancers, osteoporosis, diabetes, obesity, coronary heart disease, asthma, hypertension, thyroid conditions and multiple other metabolic disorders. In recent times, it is estimated that about 15% of the clinical drugs, used in treatments of different ailments, target nuclear receptors. These receptors include steroid/thyroid hormone receptors and orphan/adopted receptors that function as intra-cellular transcription factors to regulate expression of several hundreds of genes in response to their cognate ligands. Interestingly, nuclear receptors are also being assigned a novel role in serving as ‘epigenetic marks’ for the retention and transmission of cellular ‘transcriptional memory’. These receptors function primarily either as homodimers or heterodimers with Retinoid X Receptor (RXR) or sometimes as monomers. Being ‘drug responsive’ these receptors offer attractive targets for drug discovery since their activities can be favorably modulated by interacting ligands. However, many of the newly discovered members of this family of receptors remain incompletely understood, both in terms of physiological roles and activating ligands. In brief, nuclear receptors represent enormous potential for drug discovery and are continuously being examined to unravel the mysteries underlying their mechanisms of action. It has been well-over three decades since the cloning of steroid/nuclear receptors in the 1980s. Therefore, it’s only appropriate to prepare a comprehensive review that provides a compendium of facts and events from receptor cloning and characterization to establishment of receptor domain structures, physiological functioning and consequences of receptor malfunctioning. This review is expected to serve as a refreshing compendium of nuclear receptors for both, the beginners, as well as experts working in the areas of nuclear receptor biology.

Keywords

Classification, Diseases, Diversity, Drug Targets, Epigenetics, Nuclear Receptors, Transcription Factors, Structure.
Subscription Login to verify subscription
User
Notifications
Font Size


  • Adams MD, Celniker SE, Holt RA et al. (196 co-authors).The genome sequence of Drosophila melanogaster. Science.2000; 287:2185–95. PMid:10731132. Available from: https://doi.org/10.1126/science.287.5461.2185

  • Agoulnik IY, Cho Y, Niederberger C, Kieback DG, Cooney AJ. Cloning, expression analysis and chromosomal localization of the human nuclear receptor gene GCNF. FEBS Lett. 1998; 424(1-2):73–8. Available from: https://doi.org/10.1016/S0014-5793(98)00142-2

  • Alberti S, Steffensen KR, Gustafsson JA. Structural characterisation of the mouse nuclear oxysterol receptor genes LXRalpha and LXRbeta. Gene. 2000; 243(1-2):93–103. Available from: https://doi.org/10.1016/S0378-1119(99)00555-7

  • Alexander SP, Kelly E, Marrion N, Peters JA, Benson HE, Faccenda E, Pawson AJ, Sharman JL, Southan C, Davies JA.The Concise Guide to PHARMACOLOGY 2015/16: Nuclear hormone receptors. British Journal of Pharmacology.2015; 172:5956–78. PMid:26650443 PMCid:PMC4718213.Available from: https://doi.org/10.1111/bph.13353

  • Almasan A, Mangelsdorf DJ, Ong ES, Wahl GM, Evans RM. Chromosomal localization of the human retinoid X receptors. Genomics. 1994; 20(3):397–403. PMid:8034312.Available from: https://doi.org/10.1006/geno.1994.1193

  • André E, Conquet F, Steinmayr M, Stratton SC, Porciatti V, Becker-André M. Disruption of retinoid-related orphan receptor beta changes circadian behavior, causes retinal degeneration and leads to vacillans phenotype in mice.EMBO J. 1998; 17(14):3867–77. PMid:9670004 PMCid:PMC1170722.Available from: https://doi.org/10.1093/emboj/ 17.14.3867

  • Apfel R, Benbrook D, Lernhardt E, Ortiz MA, 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. 1995; 14(10):7025–35. Available from: https://doi.org/10.1128/MCB.14.10.7025

  • Arriza JL, Weinberger C, Cerelli G, Glaser TM, Handelin BL, Housman DE, Evans RM. Cloning of human mineralocorticoid receptor complementary DNA: Structural and functional kinship with the glucocorticoid receptor. Science.1987; 237(4812):268–75. Available from: https://doi.org/10.1126/science.3037703

  • Arthur Zelent, Andrée Krust, Martin Petkovich, Philippe Kastner and Pierre Chambon Cloning of murine α and β retinoic acid receptors and a novel receptor γ predominantly expressed in skin. Nature. 1989; 339:714–7. PMid:2544807.Available from: https://doi.org/10.1038/339714a0

  • Baes M, Gulick T, Choi HS, Martinoli MG, Simha D, Moore DD. A new orphan member of the nuclear hormone receptor superfamily that interacts with a subset of retinoic acid response elements. Mol Cell Biol. 1994; 14(3):1544– 52. PMid:8114692 PMCid:PMC358513. Available from: https://doi.org/10.1128/MCB.14.3.1544

  • Baker AR, McDonnell DP, Hughes M, Crisp TM, Mangelsdorf DJ, Haussler MR, Pike JW, Shine J, O’Malley BW.Cloning and expression of full-length cDNA encoding human vitamin D receptor. Proc. Natl Acad Sci USA. 1988; 85:3294–8. PMid:2835767 PMCid:PMC280195. Available from: https://doi.org/10.1073/pnas.85.10.3294

  • Becker-André M, André E, DeLamarter JF. Identification of nuclear receptor mRNAs by RT-PCR amplification of conserved zinc-finger motif sequences. Biochem Biophys Res Commun. 1993; 194(3):1371–9. PMid:7916608. Available from: https://doi.org/10.1006/bbrc.1993.1976

  • Bertilsson G, Heidrich J, Svensson K, Asman M, Jendeberg L, Sydow-Bäckman M, Ohlsson R, Postlind H, Blomquist P, Berkenstam A. Identification of a human nuclear receptor defines a new signaling pathway for CYP3A induction.Proc Natl Acad Sci U S A. 1998; 95(21):12208–13.PMid:9770465 PMCid:PMC22810. Available from: https:// doi.org/10.1073/pnas.95.21.12208

  • Black BE, Holaska, JM, Rastinejad F and Paschal BM. DNA binding domains in diverse nuclear receptors function as nuclear export signals. Current Biology. 2001; 11:1749– 58. Available from: https://doi.org/10.1016/S09609822(01)00537-1

  • Blumberg B, Kang H, Bolado JJr, Chen H, Craig AG, Moreno TA, Umesono K, Perlmann T, De Robertis EM, Evans RM. BXR, an embryonic orphan nuclear receptor activated by a novel class of endogenous benzoate metabolites.Genes Dev. 1998; 12(9):1269–77. PMid:9573044 PMCid: PMC316771. Available from: https://doi.org/10.1101/ gad.12.9.1269

  • Blumberg B, Sabbagh WJr, Juguilon H, Bolado JJr, van Meter CM, Ong ES, Evans RM.. SXR, a novel steroid and xenobiotic-sensing nuclear receptor. Genes Dev. 1998a; 12(20):3195–205. PMid:9784494 PMCid:PMC317212.Available from: https://doi.org/10.1101/gad.12.20.3195

  • Bonnelye E, Vanacker JM, Desbiens X, Begue A, Stehelin D, Laudet V. Rev-erb beta, a new member of the nuclear receptor superfamily, is expressed in the nervous system during chicken development. Cell Growth Differ. 1994; 5(12):1357–65. PMid:7696184.

  • Borrow J, Goddard AD, Sheer D, Solomon E. Molecular analysis of acute promyelocytic leukemia breakpoint cluster region on chromosome 17. Science. 1990; 249(4976):1577– 80. PMid:2218500. Available from: https://doi.org/10.1126/ science.2218500

  • Bourguet W, Ruff M, Chambon P, Gronemeyer H, Moras D. Crystal structure of the ligand-binding domain of the human nuclear receptor RXR-alpha. Nature. 1995; 375(6530):377–82. PMid:7760929. Available from: https:// doi.org/10.1038/375377a0

  • 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; 332:850–3. PMid:2833708. Available from: https://doi.org/10.1038/332850a0

  • Bridgham JT, Eick GN, Larroux C, Deshpande K, Harms MJ, Gauthier ME, Ortlund EA, Degnan BM, Thornton JW.Protein evolution by molecular tinkering: diversification of the nuclear receptor superfamily from a ligand-dependent ancestor. PLoS Biol. 2010; 8(10):e1000497. PMid:20957188 PMCid:PMC2950128. Available from: https://doi.org/10.1371/journal.pbio.1000497

  • Brown CJ, Goss SJ, Lubahn DB, Joseph DR, Wilson EM, French FS, Willard HF. Androgen receptor locus on the human X chromosome: regional localization to Xq11-12 and description of a DNA polymorphism. Am J Hum Genet.1989; 44(2):264–9. PMid:2563196 PMCid:PMC1715398.

  • Bunce CM, Campbell MJ. Nuclear Receptors, Current Concepts and Future Challenges. Bunce CM, Campbell MJ, editors.Nuclear Receptors an Introductory Overview. 2010.p. 1–13

  • Burmester JK, Maeda N, DeLuca HF. Isolation and expression of rat 1,25-dihydroxyvitamin D3 receptor cDNA. Proc Natl Acad Sci U S A. 1988; 85(4):1005–9. PMid:2829212 PMCid:PMC279689. Available from: https://doi.org/10.1073/pnas.85.4.1005

  • Carlberg C, van Huijsduijnen RH, Staple JK, DeLamarter JF, Becker-André M. RZRs, a new family of retinoid-related orphan receptors that function as both monomers and homodimers. Mol Endocrinol. 1994; 8(6):757–70.PMid:7935491. Available from: https://doi.org/10.1210/ me.8.6.757

  • Castillo SO, Xiao Q, Lyu MS, Kozak CA, Nikodem VM. Organization, sequence, chromosomal localization, and promoter identification of the mouse orphan nuclear receptor Nurr1 gene. Genomics. 1997; 41(2):250–7. PMid:9143501.Available from: https://doi.org/10.1006/geno.1997.4677

  • Chambon, P. A decade of molecular biology of retinoic acid receptors. FASEB J. 1996; 10(9):940–54. PMid:8801176.

  • Chang C, Da Silva SL, Ideta R, Lee Y, Yeh S, Burbach JP.Human and rat TR4 orphan receptors specify a subclass of the steroid receptor superfamily. Proc Natl Acad Sci USA.1994; 91(13):6040–4. PMid:8016112 PMCid:PMC44133.Available from: https://doi.org/10.1073/pnas.91.13.6040

  • Chang C, Kokontis J, Liao SS, Chang Y. Isolation and characterization of human TR3 receptor: a member of steroid receptor superfamily. J Steroid Biochem.1989; 34(1-6):391–5. Available from: https://doi.org/10.1016/0022-4731(89)90114-3

  • Chang C, Kokontis J. Identification of a new member of the steroid receptor super-family by cloning and sequence analysis. Biochem. Biophys. Res. Commun.1988; 155 (2): 971–7. Available from: https://doi.org/10.1016/S0006291X(88)80591-6

  • Chartier FL, Bossu JP, Laudet V, Fruchart JC, Laine B. Cloning and sequencing of cDNAs encoding the human hepatocyte nuclear factor 4 indicate the presence of two isoforms in human liver. Gene. 1994; 147(2):269–72. Available from: https://doi.org/10.1016/0378-1119(94)90079-5

  • Chen F, Figueroa DJ, Marmorstein AD, Zhang Q, Petrukhin K, Caskey CT, Austin CP. Retina-specific nuclear receptor: A potential regulator of cellular retinaldehyde-binding protein expressed in retinal pigment epithelium and Müller glial cells. Proc Natl Acad Sci U S A. 1999; 96(26):15149– 54. PMid:10611353 PMCid:PMC24788. Available from: https://doi.org/10.1073/pnas.96.26.15149

  • Chen F, Zhang Q, McDonald T, Davidoff MJ, Bailey W, Bai C, Liu Q, Caskey CT. Identification of two hERR2-related novel nuclear receptors utilizing bioinformatics and inverse PCR Gene. 1999a; 228(1-2):101–9. Available from: https:// doi.org/10.1016/S0378-1119(98)00619-2

  • Choi HS, Chung M, Tzameli I, Simha D, Lee YK, Seol W, Moore DD. Differential transactivation by two isoforms of the orphan nuclear hormone receptor CAR. J Biol Chem.1997; 272(38):23565–71. PMid:9295294. Available from: https://doi.org/10.1074/jbc.272.38.23565

  • Clark J, Benjamin H, Gill S, Sidhar S, Goodwin G, Crew J, Gusterson BA, Shipley J, Cooper CS. Fusion of the EWS gene to CHN, a member of the steroid/thyroid receptor gene superfamily, in a human myxoid chondrosarcoma.Oncogene. 1996; 12(2):229–35. PMid:8570200.

  • Dash AK, Yende AS, Kumar S, Singh SK, Kotiya D, Rana M, Tyagi RK. The Constitutive Androstane Receptor (CAR): a nuclear receptor in health and disease. J Endocrinol Reprod.2014; 18(2):59–74.

  • Dayton AI, Selden JR, Laws G, Dorney DJ, Finan J, Tripputi P, Emanuel BS, Rovera G, Nowell PC, Croce CM. A human c-erbA oncogene homologue is closely proximal to the chromosome 17 break point in acute promyelocytic leukemia. Proc Natl Acad Sci U S A. 1984; 81(14):4495–9.PMid:9295294. Available from: https://doi.org/10.1073/ pnas.81.14.4495PMid:6589608 PMCid:PMC345617

  • de Thé H, Chomienne C, Lanotte M, Degos L, Dejean A. The t(15;17) translocation of acute promyelocytic leukaemia fuses the retinoic acid receptor alpha gene to a novel transcribed locus. Nature. 1990; 347(6293):558–61. PMid:2170850.Available from: https://doi.org/10.1038/347558a0

  • Drabkin H, Kao FT, Hartz J, Hart I, Gazdar A, Weinberger C, Evans R, Gerber M. Localization of human ERBA2 to the 3p22----3p24.1 region of chromosome 3 and variable deletion in small cell lung cancer. Proc Natl Acad Sci U S A.1988; 85(23):9258–62. PMid:2848257 PMCid:PMC282718.Available from: https://doi.org/10.1073/pnas.85.23.9258

  • Drewes T, Senkel S, Holewa B, Ryffel GU. Human hepatocyte nuclear factor 4 isoforms are encoded by distinct and differentially expressed genes. Mol Cell Biol. 1996; 16(3):925–31. PMid:8622695 PMCid:PMC231074. Available from: https://doi.org/10.1128/MCB.16.3.925

  • Dumas B, Harding HP, Choi HS, Lehmann KA, Chung M, Lazar MA, Moore DD. A new orphan member of the nuclear hormone receptor superfamily closely related to Rev-Erb Mol Endocrinol. 1994; 8:996–1005. PMid:7997240. Available from: https://doi.org/10.1210/mend.8.8.7997240

  • Enmark E, Kainu T, Pelto-Huikko M, Gustafsson JA. Identification of a novel member of the nuclear receptor superfamily which is closely related to Rev-ErbA. Biochem Biophys Res Commun. 1994; 204(1):49–56. PMid:7945391.Available from: https://doi.org/10.1006/bbrc.1994.2424

  • Enmark E, Pelto-Huikko M, Grandien K, Lagercrantz S, Lagercrantz J, Fried G, Nordenskjöld M, Gustafsson JA. Human estrogen receptor beta-gene structure, chromosomal localization, and expression pattern. J Clin Endocrinol Metab.1997; 82(12):4258–65. PMid:9398750. Available from: https://doi.org/10.1210/jcem.82.12.4470

  • Eudy JD, Yao S, Weston MD, Ma-Edmonds M, Talmadge CB, Cheng JJ, Kimberling WJ, Sumegi J. Isolation of a gene encoding a novel member of the nuclear receptor superfamily from the critical region of Usher syndrome type IIa at 1q41. Genomics. 1998; 50(3):382–4. PMid:9676434.Available from: https://doi.org/10.1006/geno.1998.5345

  • Evans RM, Mangelsdorf DJ. Nuclear Receptors, RXR, and the Big Bang. Cell. 2014; 157(1):255–66. PMid:24679540 PMCid:PMC4029515. Available from: https://doi.org/10.1016/j.cell.2014.03.012

  • Evans RM. Journal of Molecular Endocrinology 25th anniversary special issue. J Mol Endocrinol. 2013; 51:E1–E3.PMid:24280960. Available from: https://doi.org/10.1530/ JME-13-0257

  • Fan YS, Eddy RL, Byers MG, Haley LL, Henry WM, Nowak NJ, Shows TB. 1989. The human mineralocorticoid receptor gene (MLR) is located on chromosome 4 at q31.2.Cytogenet Cell Genet. 1989; 52(1-2):83–4. PMid:2558856.Available from: https://doi.org/10.1159/000132846

  • Forman BM, Chen J, Blumberg B, Kliewer SA, Henshaw R, Ong ES and Evans RM. Cross-Talk among RORal and the Rev-erb Family of Orphan Nuclear Receptors. Mol. Endocrinol.1994; 8:1253–61. PMid:7838158. Available from: https://doi.org/10.1210/mend.8.9.7838158

  • Forman BM, Goode E, Chen J, Oro AE, Bradley DJ, Perlmann T, Noonan DJ, Burka LT, McMorris T, Lamph WW, Evans RM, Weinberger C. Identification of a nuclear receptor that is activated by farnesol metabolites.Cell. 1995; 81(5):687–93. Available from: https://doi.org/10.1016/0092-8674(95)90530-8

  • Francis GA, Fayard E, Picard F, Auwerx J. Nuclear receptors and the control of metabolism. Annu Rev Physiol. 2003; 65:261–311. PMid:12518001. Available from: https://doi.org/10.1146/annurev.physiol.65.092101.142528

  • Francke U, Foellmer BE. The glucocorticoid receptor gene is in 5q31-q32 [corrected]. Genomics. 1989; 4(4):610612. Available from: https://doi.org/10.1016/08887543(89)90287-5

  • Galarneau L, Drouin R, Bélanger L. Assignment of the fetoprotein transcription factor gene (FTF) to human chromosome band 1q32.11 by in situ hybridization. Cytogenet Cell Genet. 1998; 82(3-4):269–70. PMid:9858833.: https:// doi.org/10.1159/000015116

  • Germain P, Staels B, Dacquet C, Spedding M, Laudet V.Overview of nomenclature of nuclear receptors. Pharmacol.Rev. PMid:17132848. 2006; 58(4):685–704. Available from: https://doi.org/10.1124/pr.58.4.2

  • Giguere V, S. Ong E, Segui P, Evans RM. Identification of a receptor for the morphogen retinoic acid. Nature. 1987; 330:624–9. PMid:2825036. Available from: https://doi.org/10.1038/330624a0

  • Giguère V, Tini M, Flock G, Ong E, Evans RM, Otulakowski G. Isoform-specific amino-terminal domains dictate DNA-binding properties of ROR alpha, a novel family of orphan hormone nuclear receptors. Genes Dev. 1994; 8(5):538–53. PMid:7926749. Available from: https://doi.org/10.1101/gad.8.5.538

  • Giguère V, Yang N, Segui P, Evans RM. Identification of a new class of steroid hormone receptors. Nature. 1988; 331(6151):91–4. PMid:3267207. Available from: https:// doi.org/10.1038/331091a0

  • Green S, Walter P, Kumar V, Krust A, Bornert JM, Argos P, Chambon P. Human oestrogen receptor cDNA:sequence, expression and homology to v-erb-A. Nature.1986; 320(6058):134–9. Available from: https://doi.org/10.1038/320134a0

  • Greene GL, Gilna P, Waterfield M, Baker A, Hort Y, Shine J. Sequence and expression of human estrogen receptor complementary DNA. Science. 1986; 231(4742):1150–4.PMid:3753802. Available from: https://doi.org/10.1126/science.3753802

  • Greene ME, Blumberg B, McBride OW, Yi HF, Kronquist K, Kwan K, Hsieh L, Greene G, Nimer SD. Isolation of the human peroxisome proliferator activated receptor gamma cDNA: expression in hematopoietic cells and chromosomal mapping. Gene Expr. 1995; 4(4-5):281–99.PMid:7787419.

  • Gronemeyer H, Laudet V. Transcription factors 3: nuclear receptors. Protein Profile. 1995; 2(11):1173–308.PMid:8681033.

  • Guiochon-Mantel A, Delabre K, Lescop P, Milgrom E. Nuclear localization signals also mediate the outward movement of proteins from the nucleus. Proc Natl Acad Sci U S A.1994; 91(15):7179–83. PMid:8041765 PMCid:PMC44362.Available from: https://doi.org/10.1073/pnas.91.15.7179

  • Haider NB, Jacobson SG, Cideciyan AV, Swiderski R, Streb LM, Searby C, Beck G, Hockey R, Hanna DB, Gorman S, Duhl D, Carmi R, Bennett J, Weleber RG, Fishman GA, Wright AF, Stone EM, Sheffield VC. Mutation of a nuclear receptor gene, NR2E3, causes enhanced S cone syndrome, a disorder of retinal cell fate. Nat Genet. 2000; 24(2):127–31. PMid:10655056. Available from: https://doi.org/10.1038/72777

  • Hamada K, Gleason SL, Levi BZ, 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; 86(21):8289–93. PMid:2554307 PMCid:PMC298266.Available from: https://doi.org/10.1073/pnas.86.21.8289

  • Hamilton BA, Frankel WN, Kerrebrock AW, Hawkins TL, FitzHugh W, Kusumi K, Russell LB, Mueller KL, van Berkel V, Birren BW, Kruglyak L, Lander ES. Disruption of the nuclear hormone receptor RORalpha in staggerer mice.Nature. 1996; 379(6567):736–9. PMid:8602221. Available from: https://doi.org/10.1038/379736a0

  • Hanna RN, Leo MC, Harper GH, Dominika N, Angela MG, Jennifer AP, Frederic G, Catherine CH. The Transcription Factor NR4A1 (Nur77) Controls Bone Marrow Differentiation and the Survival of Ly6C- Monocytes. Nature Immunology. 2011; 12(8):778–85. PMid:21725321 PMCid: PMC3324395. Available from: https://doi.org/10.1038/ ni.2063

  • Hedvat CV, Irving SG. The isolation and characterization of MINOR, a novel mitogen-inducible nuclear orphan receptor.Mol Endocrinol. 1995; 9(12):1692–700. Available from: https://doi.org/10.1210/mend.9.12.8614405

  • Hirose T, Fujimoto W, Tamaai T, Kim KH, Matsuura H, Jetten AM. TAK1: Molecular cloning and characterization of a new member of the nuclear receptor superfamily. Mol Endocrinol. 1994; 8(12):1667–80. PMid:7708055. Available from: https://doi.org/10.1210/mend.8.12.7708055

  • Hirose T, Smith RJ, Jetten AM. ROR gamma: The third member of ROR/RZR orphan receptor subfamily that is highly expressed in skeletal muscle. Biochem Biophys Res Commun. 1994a; 205(3):1976–83. Available from: https:// doi.org/10.1006/bbrc.1994.2902PMid:7811290

  • Hollenberg SM, Weinberger C, Ong ES, Cerelli G, Oro A, Lebo R, Thompson EB, Rosenfeld MG, Evans RM. Primary structure and expression of a functional human glucocorticoid receptor cDNA. Nature. 1985; 318(6047):635–41. PMid:2867473. Available from: https:// doi.org/10.1038/318635a0

  • Hong H, Yang L, Stallcup MR. Hormone-independent transcriptional activation and coactivator binding by novel orphan nuclear receptor ERR3. J Biol Chem. 1999; 274(32):22618–26. PMid:10428842. Available from: https://doi.org/10.1074/jbc.274.32.22618

  • Ishikawa T, Umesono K, Mangelsdorf DJ, Aburatani H, Stanger BZ, Shibasaki Y, Imawari M, Evans RM, Takaku F.A functional retinoic acid receptor encoded by the gene on human chromosome 12. Mol Endocrinol. 1990; 4(6):837– 44. PMid:2172793. Available from: https://doi.org/10.1210/ mend-4-6-837

  • Jackson A, Panayiotidis P, Foroni L. The human homologue of the Drosophila tailless gene (TLX): characterization and mapping to a region of common deletion in human lymphoid leukemia on chromosome 6q21. Genomics. 1998;50(1):34–43. PMid:9628820. Available from: https://doi.org/10.1006/geno.1998.5270

  • Jones KA, Fitzgibbon J, Woodward KJ, Goudie D, FergusonSmith MA, Povey S, Wolfe J, Solomon E. Localization of the retinoid X receptor alpha gene (RXRA) to chromosome 9q34. Ann Hum Genet. 1993; 57(Pt 3):195–201. PMid:8257089. Available from: https://doi.org/10.1111/j.1469-1809.1993.tb01595.x

  • Kanno, Y, Inouye Y. Molecular basis of the intracellular localization of the Constitutive Androstane Receptor (CAR).Journal of Health Science. 2008; 54(3):261–6. Available from: https://doi.org/10.1248/jhs.54.261

  • Khan SA, Vanden Heuvel JP. Role of nuclear receptors in the regulation of gene expression by dietary fatty acids (review).J Nutr Biochem. 2003; 14:554–67. Available from: https://doi.org/10.1016/S0955-2863(03)00098-6

  • Kliewer SA, Forman BM, Blumberg B, Ong ES, Borgmeyer U, Mangelsdorf DJ, Umesono K, Evans RM. Differential expression and activation of a family of murine peroxisome proliferator-activated receptors. Proc Natl Acad Sci U S A.1994; 91(15):7355–9. PMid:8041794 PMCid:PMC44398.Available from: https://doi.org/10.1073/pnas.91.15.7355

  • Kliewer SA, Moore JT, Wade L, Staudinger JL, Watson MA, Jones SA, McKee DD, Oliver BB, Willson TM, Zetterström RH, Perlmann T, Lehmann JM. An orphan nuclear receptor activated by pregnanes defines a novel steroid signaling pathway. Cell. 1998; 92(1):73–82. Available from: https:// doi.org/10.1016/S0092-8674(00)80900-9

  • Kobayashi M, Takezawa S, Hara K, Yu RT, Umesono Y, Agata K, Taniwaki M, Yasuda K, Umesono K. Identification of a photoreceptor cell-specific nuclear receptor. Proc Natl Acad Sci U S A. 1999; 96(9):4814–9. PMid:10220376 PMCid: PMC21774. Available from: https://doi.org/10.1073/ pnas.96.9.4814

  • Koh YS, Moore DD. Linkage of the nuclear hormone receptor genes NR1D2, THRB, and RARB: evidence for an ancient, large-scale duplication. Genomics. 1999; 57(2):289–92. PMid:10198169. Available from: https://doi.org/10.1006/geno.1998.5683

  • Krust A, Green S, Argos P, Kumar V, Walter P, Bornert JM, Chambon P. The chicken oestrogen receptor sequence: homology with v-erbA and the human oestrogen and glucocorticoid receptors. EMBO J. 1986; 5(5):891–7. PMid:3755102 PMCid:PMC1166879.

  • Krust A, Kastner P, Petkovich M, Zelent A, Chambon P. A third human retinoic acid receptor, hRAR-gamma. Proc Natl Acad Sci U S A. 1989; 86(14):5310–4. PMid:2546152 PMCid:PMC297611. Available from: https://doi.org/10.1073/pnas.86.14.5310

  • Kumar S, Saradhi M, Chaturvedi NK, Tyagi RK. Intracellular localization and nucleocytoplasmic trafficking of steroid receptors: an overview. Mol Cell Endocrinol. 2006; 246(12):147–56. PMid:16388893. Available from: https://doi.org/10.1016/j.mce.2005.11.028

  • Kumar S, Saradhi M, Chaturvedi NK, Tyagi RK. Retention and transmission of active transcription memory from progenitor to progeny cells via ligand-modulated transcription factors: elucidation of a concept by BIOPIT model. Cell Biol Int. 2012; 36(2):177–82. PMid:22007870. Available from: https://doi.org/10.1042/CBI20090329

  • Labelle Y, Bussières J, Courjal F, Goldring MB. The EWS/ TEC fusion protein encoded by the t(9;22) chromosomal translocation in human chondrosarcomas is a highly potent transcriptional activator. Oncogene. 1999; 18(21):3303–8.PMid:10359536. https://doi.org/10.1038/sj.onc.1202675

  • Labelle Y, Zucman J, Stenman G, Kindblom LG, Knight J, Turc-Carel C, Dockhorn-Dworniczak B, Mandahl N, Desmaze C, Peter M, et al. Oncogenic conversion of a novel orphan nuclear receptor by chromosome translocation. Hum Mol Genet. 1995; 4(12):2219–26. PMid:8634690. Available from: https://doi.org/10.1093/hmg/4.12.2219

  • Ladias JA, Karathanasis SK. Regulation of the apolipoprotein AI gene by ARP-1, a novel member of the steroid receptor superfamily. Science. 1991; 251(4993):561–5.PMid:1899293. Available from: https://doi.org/10.1126/science.1899293

  • Laudet V, Gronemeyer H. The Nuclear Receptors FactsBook. London, UK: Academic Press; 2002.

  • Law ML, Kao FT, Wei Q, Hartz JA, Greene GL, ZaruckiSchulz T, Conneely OM, Jones C, Puck TT, O’Malley BW, et al. The progesterone receptor gene maps to human chromosome band 11q13, the site of the mammary oncogene int-2. Proc Natl Acad Sci U S A. 1987; 84(9):2877– 81. PMid:3472240 PMCid:PMC304763. Available from: https://doi.org/10.1073/pnas.84.9.2877

  • Law SW, Conneely OM, O’Malley BW. Molecular cloning of a novel member of the nuclear receptor superfamily related to the orphan receptor, TR2. Gene Expr. 1994; 4(1-2):77– 84. PMid:7841789

  • Lazar MA, Hodin RA, Darling DS, Chin WW. A Novel Member of the Thyroid/Steroid Hormone Receptor Family Is Encoded by the Opposite Strand of the Rat c-erbAot Transcriptional Unit. Mol. Cell. Biol. 1989; 9(3):1128–36.PMid:2542765 PMCid:PMC362703. Available from:https://doi.org/10.1128/MCB.9.3.1128

  • Le Beau MM, Song C, Davis EM, Hiipakka RA, Kokontis JM, Liao S. Assignment of the human ubiquitous receptor gene (UNR) to 19q13.3 using fluorescence in situ hybridization.Genomics. 1995; 26(1):166–8. Available from: https://doi.org/10.1016/0888-7543(95)80100-Z

  • le Maire A, Bourguet W, Balaguer P. A structural view of nuclear hormone receptor: endocrine disruptor interactions.Cell Mol Life Sci. 2010; 67(8):1219–37. PMid:20063036.Available from: https://doi.org/10.1007/s00018-009-0249-2

  • Lee HK, Lee YK, Park SH, Kim YS, Park SH, Lee JW, Kwon HB, Soh J, Moore DD, Choi HS. Structure and expression of the orphan nuclear receptor SHP gene. J Biol Chem. 1998; 273(23):14398–402. PMid:9603951. Available from: https:// doi.org/10.1074/jbc.273.23.14398

  • Lee YF, Shyr CR, Thin TH, Lin WJ, Chang C. Convergence of two repressors through heterodimer formation of androgen receptor and testicular orphan receptor-4: a unique signaling pathway in the steroid receptor superfamily.Proc Natl Acad Sci U S A. 1999; 96(26):14724–9.PMid:10611280 PMCid:PMC24715. Available from:https://doi.org/10.1073/pnas.96.26.14724

  • Lehmann JM, McKee DD, Watson MA, Willson TM, Moore JT, Kliewer SA. The human orphan nuclear receptor PXR is activated by compounds that regulate CYP3A4 gene expression and cause drug interactions. J Clin Invest.1998; 102(5):1016–23. PMid:9727070 PMCid:PMC508967.Available from: https://doi.org/10.1172/JCI3703

  • Leid M, Kastner P, Lyons R, Nakshatri H, Saunders M, Zacharewski T, Chen JY, Staub A, Garnier JM, Mader S, et al. Purification, cloning, and RXR identity of the HeLa cell factor with which RAR or TR heterodimerizes to bind target sequences efficiently. Cell. 1992; 68(2):377–95. Available from: https://doi.org/10.1016/0092-8674(92)90478-U

  • Lubahn DB, Joseph DR, Sar M, Tan J, Higgs HN, Larson RE, French FS, Wilson EM. The human androgen receptor: complementary deoxyribonucleic acid cloning, sequence analysis and gene expression in prostate. Mol Endocrinol.1988; 2(12):1265–75. PMid:3216866. Available from: https://doi.org/10.1210/mend-2-12-1265

  • Mages HW, Rilke O, Bravo R, Senger G, Kroczek RA. NOT, a human immediate-early response gene closely related to the steroid/thyroid hormone receptor NAK1/TR3. Mol Endocrinol.1994: 8(11):1583–91. PMid:7877627. Available from: https://doi.org/10.1210/mend.8.11.7877627

  • Maglich JM, a Sluder XG, Y Shi, D DM, Carrick K, Kamdar K, Willson TM, Moore JT. Comparison of complete nuclear receptor sets from the human, caenorhabditis elegans and drosophila genomes. Genome Biology. 2001; 2(8):RESEARCH0029.

  • Mangelsdorf DJ, Borgmeyer U, Heyman RA, Zhou JY, Ong ES, Oro AE, Kakizuka A, Evans RM. Characterization of three RXR genes that mediate the action of 9-cis retinoic acid. Genes Dev. 1992; 6(3):329–44. PMid:1312497. https:// doi.org/10.1101/gad.6.3.329

  • Mangelsdorf DJ, Ong ES, Dyck JA, Evans RM. Nuclear receptor that identifies a novel retinoic acid response pathway.Nature. 1990; 345(6272):224–9. PMid:2159111. Available from: https://doi.org/10.1038/345224a0

  • Mattei MG, Krust A, Stropp U, Mattei JF, Chambon P. As signment of the human progesterone receptor to the q22 band of chromosome 11. Hum Genet. 1988; 78(1):96–7.PMid:3338797. Available from: https://doi.org/10.1007/ BF00291245

  • Mattei MG, Rivière M, Krust A, Ingvarsson S, Vennström B, Islam MQ, Levan G, Kautner P, Zelent A, Chambon P, et al. Chromosomal assignment of retinoic acid receptor (RAR) genes in the human, mouse, and rat genomes. Genomics.1991; 10(4):1061–9. Available from: https://doi.org/10.1016/0888-7543(91)90199-O

  • McDonnell DP, Mangelsdorf DJ, Pike JW, Haussler MR, O’Malley BW. Molecular cloning of complementary DNA encoding the avian receptor for vitamin D. Science. 1987; 235(4793):1214–7. PMid:3029866. Available from: https:// doi.org/10.1126/science.3029866

  • Medvedev A, Chistokhina A, Hirose T, Jetten AM. Genomic structure and chromosomal mapping of the nuclear orphan receptor ROR gamma (RORC) gene. Genomics. 1997; 46(1):93–102. PMid:9403063. Available from: https://doi.org/10.1006/geno.1997.4980

  • Menasce LP, White GR, Harrison CJ, Boyle JM. Localization of the estrogen receptor locus (ESR) to chromosome 6q25.1 by FISH and a simple post-FISH banding technique.Genomics. 1993; 17(1):263–5. PMid:8406468. Available from:https://doi.org/10.1006/geno.1993.1320

  • Misrahi M, Atger M, d’Auriol L, Loosfelt H, Meriel C, Fridlansky F, Guiochon-Mantel A, Galibert F, Milgrom E. Complete amino acid sequence of the human progesterone receptor deduced from cloned cDNA. Biochem Biophys ResCommun. 1987; 143(2):740–8. Available from: https://doi.org/10.1016/0006-291X(87)91416-1

  • Mitelman F, Manolov G, Manolova Y, Billström R, Heim S, Kristoffersson U, Mandahl N, Ferro MT, San Roman C.High resolution chromosome analysis of constitutional and acquired t(15;17) maps c-erbA to subband 17q11.2. Cancer Genet Cytogenet. 1986; 22(2):95–8. Available from: https:// doi.org/10.1016/0165-4608(86)90168-8

  • Miyajima N, Horiuchi R, Shibuya S, Matsubara K, Toyoshima K, Yamamoto T. Two erbA homologs encoding proteins with different T (3) binding capacities are transcribed from opposite DNA strands of the same genetic locus. Cell. 1989; 57:31–9. Available from: https://doi.org/10.1016/00928674(89)90169-4

  • Miyajima N, Kadowaki Y, Fukushige S, Shimizu S, Semba K, Yamanashi Y, Matsubara K, Toyoshima K, and Yamamoto T. Identification of two novel members of erbA superfamily by molecular cloning: the gene products of the two are highly related to each other. Nucleic Acids Res. 1988; 16:11057–74. PMid:2905047 PMCid:PMC338996. Available from: https://doi.org/10.1093/nar/16.23.11057

  • Monaghan AP, Grau E, Bock D, Schütz G. The mouse homolog of the orphan nuclear receptor tailless is expressed in the developing forebrain. Development. 1995; 121(3):839– 53. PMid:7720587.

  • Montano MM, Müller V, Trobaugh A, Katzenellenbogen BS. The carboxy-terminal F domain of the human estrogen receptor: role in the transcriptional activity of the receptor and the effectiveness of antiestrogens as estrogen antagonists.Mol Endocrinol. 1995; 9(7):814–25.PMid:7476965.Available from: https://doi.org/10.1210/me.9.7.814

  • Moras D, Gronemeyer H. The nuclear receptor ligand-binding domain: structure and function. Curr Opin Cell Biol.1998; 10(3):384-391. https://doi.org/10.1016/S09550674(98)80015-X

  • Morrison N, Harrap SB, Arriza JL, Boyd E, Connor JM.Regional chromosomal assignment of the human mineralocorticoid receptor gene to 4q31.1. Hum Genet. 1990;85(1):130–2. PMid:2162806. Available from: https://doi.org/10.1007/BF00276340

  • Nichols M, Rientjes JM, Stewart AF. Different positioning of the ligand-binding domain helix 12 and the F domain of the estrogen receptor accounts for functional differences between agonists and antagonists. EMBO J. 1998; 17(3):765–73. PMid:9451001 PMCid:PMC1170425. Available from: https://doi.org/10.1093/emboj/17.3.765

  • Novac N, Heinzel T. Nuclear Receptors: Overview and Classification. Current Drug Targets - Inflammation and Allergy. 2004; 3(4):339. Available from: https://doi.org/10.2174/1568010042634541

  • Ogawa S, Inoue S, Watanabe T, Hiroi H, Orimo A, Hosoi T, Ouchi Y, Muramatsu M. The complete primary structure of human estrogen receptor beta (hER beta) and its heterodimerization with ER alpha in vivo and in vitro.Biochem Biophys Res Commun. 1998; 243(1):122–6.Available from: https://doi.org/10.1006/bbrc.1997.7893 PMid:9473491

  • Ortiz MA, Piedrafita FJ, Pfahl M, Maki R. TOR: a new orphan receptor expressed in the thymus that can modulate retinoid and thyroid hormone signals. Molecular Endocrinology.1995:9(12):1679–91. PMid:8614404. Available from: https://doi.org/10.1210/me.9.12.1679

  • Otte K, Kranz H, Kober I, Thompson P, Hoefer M, Haubold B, Remmel B, Voss H, Kaiser C, Albers M, Cheruvallath Z, Jackson D, Casari G, Koegl M, Paabo S, Mous J, Kremoser C. Deuschle U. Identification of farnesoid X receptor β as a novel mammalian nuclear receptor sensing lanosterol.Mol Cell Biol. 2003; 23:864–72. PMid:12529392 PMCid: PMC140718. Available from: https://doi.org/10.1128/ MCB.23.3.864-872.2003

  • Papetti M, Wood N, Lohmar PD, Bowman MR. The identification of the cDNA coding for HRR-1, a novel humanfarnesol receptor. Submitted (AUG-1996) to the EMBL/ GenBank/ DDBJ databases.

  • Pe-a de Ortiz S, Cannon MM, Jamieson GA Jr. Expression of nuclear hormone receptors within the rat hippocampus: identification of novel orphan receptors. Brain Res Mol Brain Res. 1994; 23(3):278–83. Available from: https://doi.org/10.1016/0169-328X(94)90235-6

  • Peters GA, Khan SA. Estrogen receptor domains E and F: role in dimerization and interaction with coactivator RIP140. Mol Endocrinol. 1999; 13(2):286–96. PMid:9973258 Available from: https://doi.org/10.1210/mend.13.2.0244

  • Petkovich M, Brand NJ, Krust A, Chambon P. A human retinoic acid receptor which belongs to the family of nuclear receptors. Nature. 1987; 330(6147):444–50. PMid:2825025.Available from: https://doi.org/10.1038/330444a0

  • Pettersson K, Svensson K, Mattsson R, Carlsson B, Ohlsson R, Berkenstam A. Expression of a novel member of estrogen response element-binding nuclear receptors is restricted to the early stages of chorion formation during mouse embryogenesis. Mech Dev. 1996; 54(2):211–23. Available from: https://doi.org/10.1016/0925-4773(95)00479-3

  • Pignoni F, Baldarelli RM, Steingrímsson E, Diaz RJ, Patapoutian A, Merriam JR, Lengyel JA. The Drosophila gene tailless is expressed at the embryonic termini and is a member of the steroid receptor superfamily.Cell. 1990; 62(1):151–63. Available from: https://doi.org/10.1016/0092-8674(90)90249-E

  • Prakash C, Zuniga B, Song CS, Jiang S, Cropper J, Park S, Chatterjee B. Nuclear Receptors in Drug Metabolism, Drug Response and Drug Interactions. Nuc Receptor Res. 2015; 2.

  • Qiu Y, Krishnan V, Zeng Z, Gilbert DJ, Copeland NG, Gibson L, Yang-Feng T, Jenkins NA, Tsai MJ, Tsai SY.. Isolation, characterization, and chromosomal localization of mouse and human COUP-TF I and II genes. Genomics. 1995; 29(1):240–46. PMid:8530078. Available from: https://doi.org/10.1006/geno.1995.1237

  • Rana M, Devi S, Gourinath S, Goswami R, Tyagi RK. A comprehensive analysis and functional characterization of naturally occurring non-synonymous variants of nuclear receptor PXR. Biochim Biophys Acta. Available from: 2016; 1859(9):1183–97.

  • Reitzel AM, Pang K, Ryan JF, Mullikin JC, Martindale MQ, Baxevanis AD, Tarrant AM. Nuclear receptors from the ctenophore Mnemiopsis leidyi lack a zinc-finger DNA-binding domain: lineage-specific loss or ancestral condition in the emergence of the nuclear receptor superfamily? Evodevo.Available from: 2011; 2(1):3. PMid:21291545 PMCid:PMC3038971.Available from: https://doi.org/10.1186/2041-9139-2-3

  • Renaud JP, Rochel N, Ruff M, Vivat V, Chambon P, Gronemeyer H, Moras D. Crystal structure of the RAR-gamma ligand-binding domain bound to all-trans retinoic acid.Nature. 1995; 378:681–9. PMid:7501014. Available from: https://doi.org/10.1038/378681a0

  • Retnakaran R, Flock G, Giguère V. Identification of RVR, a novel orphan nuclear receptor that acts as a negative transcriptional regulator. Mol Endocrinol. 1994; 8(9):1234–44.PMid:7838156. Available from: https://doi.org/10.1210/ me.8.9.1234

  • Robinson-Rechavi M, Carpentier AS, Duffraisse M, Laudet V. How many nuclear hormone receptors are there in the human genome? Trends Genet. 2001; 17(10):554–6. Available from: https://doi.org/10.1016/S0168-9525(01)02417-9

  • Robinson-Rechavi M, Garcia HE, Laude V. The nuclear receptor Superfamily. Journal of Cell Science. 2003; 116:585– 6. PMid:12538758. Available from: https://doi.org/10.1242/ jcs.00247

  • Romagnolo DF, Zempleni J, Selmin OI. Nuclear receptors and epi- genetic regulation: opportunities for nutritional targeting and dis- ease prevention. Advances in nutrition.2014; 5:373–85. PMid:25022987 PMCid:PMC4085186.Available from: https://doi.org/10.3945/an.114.005868

  • Rousseau-Merck MF, Misrahi M, Loosfelt H, Milgrom E, Berger R. Localization of the human progesterone receptor gene to chromosome 11q22-q23. Hum Genet. 1987; 77(3):280–82. PMid:3679212. Available from: https://doi.org/10.1007/BF00284486

  • Rowe A, Eager NS, Brickell PM. A member of the RXR nuclear receptor family is expressed in neural-crest-derived cells of the developing chick peripheral nervous system.Development. 1991; 111(3):771–8. PMid:1652422.

  • Sap J, Mu-oz A, Damm K, Goldberg Y, Ghysdael J, Leutz A, Beug H, Vennström B. The c-erb-A protein is a high-affinity receptor for thyroid hormone. Nature. 1986; 324(6098):635–40. PMid:2879242. Available from: https:// doi.org/10.1038/324635a0

  • Schmidt A, Endo N, Rutledge SJ, Vogel R, Shinar D, Rodan GA. Identification of a new member of the steroid hormone receptor superfamily that is activated by a peroxisome proliferator and fatty acids. Mol Endocrinol. 1992; 6(10):1634– 41. PMid:1333051. Available from: https://doi.org/10.1210/ mend.6.10.1333051

  • Seol W, Choi HS, Moore DD. Isolation of proteins that interact specifically with the retinoid X receptor: two novel orphan receptors. Mol Endocrinol. 1995; 9(1):72–85.PMid:7760852. Available from: https://doi.org/10.1210/ me.9.1.72

  • Seol W, Choi HS, Moore DD. An orphan nuclear hormone receptor that lacks a DNA binding domain and heterodimerizes with other receptors. Science. 1996; 272(5266):1336–9. PMid:8650544. Available from: https:// doi.org/10.1126/science.272.5266.1336

  • Sher T, Yi HF, McBride OW, Gonzalez FJ. cDNA cloning, chromosomal mapping, and functional characterization of the human peroxisome proliferator activated receptor. Biochemistry. 1993; 32(21):5598-5604. PMid:7684926. Available from: https://doi.org/10.1021/bi00072a015

  • Shi H, Shigeta H, Yang N, Fu K, O’Brian G, Teng CT. Human estrogen receptor-like 1 (ESRL1) gene: Genomic organization, chromosomal localization, and promoter characterization.Genomics. 1997: 44(1):52–60. PMid:9286700.Available from: https://doi.org/10.1006/geno.1997.4850

  • Shinar DM, Endo N, Rutledge SJ, Vogel R, Rodan GA, Schmidt A. NER, a new member of the gene family encoding the human steroid hormone nuclear receptor.Gene. 1994; 147(2):273–6. Available from: https://doi.org/10.1016/0378-1119(94)90080-9

  • Siisens U, Borgmeyer U. Characterization of the human germ cell nuclear factor gene. Biochim Biophys Acta. 1996; 1309(3):179-182. Available from: https://doi.org/10.1016/ S0167-4781(96)00157-1

  • Sladek FM, Ruse MD Jr, Nepomuceno L, Huang SM, Stallcup MR. Modulation of transcriptional activation and coactivator interaction by a splicing variation in the F domain of nuclear receptor hepatocyte nuclear factor 4alpha1.Mol Cell Biol. 1999; 19(10):650922. PMid:10490591 PMCid: PMC84621. Available from: https://doi.org/10.1128/ MCB.19.10.6509

  • Sladek FM. What are nuclear receptor ligands? MolCell Endocrinol.2011: 334:03–13.

  • Sladek R, Beatty B, Squire J, Copeland NG, Gilbert DJ, Jenkins NA, Giguère V. Chromosomal mapping of the human and murine orphan receptors ERRalpha (ESRRA) and ERRbeta (ESRRB) and identification of a novel human ERRalpharelated pseudogene. Genomics. 1997; 45(2):320–6.PMid:9344655. https://doi.org/10.1006/geno.1997.4939

  • Sluder AE, Maina CV. Nuclear receptors in nematodes: themes and variations. Trends in Genetics:TIG. 2001; 17(4):206–13. Available from: https://doi.org/10.1016/ S0168-9525(01)02242-9

  • Smirnov AN. Nuclear receptors: nomenclature, ligands, mechanisms of their effects on gene expression. Biochemistry (Mosc). 2002; 67:957–77. Available from: https://doi.org/10.1023/A:1020545200302

  • Smith DP, Mason CS, Jones EA, Old RW. A novel nuclear receptor superfamily member in Xenopus that associates with RXR, and shares extensive sequence similarity to the mammalian vitamin D3 receptor. Nucleic Acids Res. 1994; 22(1):66–71. PMid:8127656 PMCid:PMC307747. Available from: https://doi.org/10.1093/nar/22.1.66

  • Song C, Kokontis JM, Hiipakka RA, Liao S. Ubiquitous receptor: a receptor that modulates gene activation by retinoic acid and thyroid hormone receptors. Proc Natl Acad Sci U S A. 1994; 91(23):10809–13. PMid:7971966 PMCid: PMC45115. Available from: https://doi.org/10.1073/ pnas.91.23.10809

  • Spurr NK, Solomon E, Jansson M, Sheer D, Goodfellow PN, Bodmer WF, Vennstrom B. Chromosomal localisation of the human homologues to the oncogenes erb A and B.EMBO J. 1984; 3(1):159–63. PMid:6323162 PMCid:PMC557313.

  • Szpirer J, Szpirer C, Riviere M, Levan G, Marynen P, Cassiman JJ, Wiese R, DeLuca HF. The Sp1 transcription factor gene (SP1) and the 1,25-dihydroxyvitamin D3 receptor gene (VDR) are colocalized on human chromosome arm 12q and rat chromosome 7. Genomics. 1991; 11(1):168–73. Available from: https://doi.org/10.1016/0888-7543(91)90114-T

  • Taymans SE, Pack S, Pak E, Orban Z, Barsony J, Zhuang Z, Stratakis CA. The human vitamin D receptor gene (VDR) is localized to region 12cen-q12 by fluorescent in situ hybridization and radiation hybrid mapping: genetic and physical VDR map. J Bone Miner Res. 1999; 14(7):1163–6. PMid:10404016. Available from: https://doi.org/10.1359/ jbmr.1999.14.7.1163

  • Tchenio T, Segal-Bendirdjian E, Heidmann T. Generation of processed pseudogenes in murine cells. EMBO J. 1993; 12:1487–97. PMid:8385606 PMCid:PMC413361

  • Theriault A, Boyd E, Harrap SB, Hollenberg SM, Connor JM. Regional chromosomal assignment of the human glucocorticoid receptor gene to 5q31. Hum Genet. 1989; 83(3):289–91. PMid:2793174. Available from: https://doi.org/10.1007/BF00285175

  • Tian Y. Epigenetic regulation of pregnane X receptor activity.Drug Metab Rev. 2013; 45(2):166–72. PMid:23600685.Available from: https://doi.org/10.3109/03602532.2012.756 012

  • Torii T, Kawarai T, Nakamura S, Kawakami H. Organization of the human orphan nuclear receptor Nurr1 gene.Gene. 1999; 230(2):225–32. Available from: https://doi.org/10.1016/s0378-1119(99)00064-5

  • Tsai MJ, O’Malley BW. Molecular mechanisms of action of steroid/thyroid receptor superfamily members. Annu Rev Biochem. 1994; 63:451–86. PMid:7979245. Available from:https://doi.org/10.1146/annurev.bi.63.070194.002315

  • Tyagi RK, Amazit L, Lescop P, Milgrom E, Guiochon-Mantel A. Mechanisms of Progesterone Receptor Export from Nuclei: Role of Nuclear Localization Signal, Nuclear Export Signal, and Ran Guanosine Triphosphate. Molecular Endocrinology.1998; 12(11):1684–94. PMid:9817595. Available from: https://doi.org/10.1210/mend.12.11.0197

  • Wagner RL, Apriletti JW, McGrath ME, West BL, Baxter JD, Fletterick RJ. A structural role for hormone in the thyroid hormone receptor. Nature. 1995; 378(6558):690–7. PMid:7501015. Available from: https:// doi.org/10.1038/378690a0

  • Wang LH, Tsai SY, Cook RG, Beattie WG, Tsai MJ, O’Malley BW. COUP transcription factor is a member of the steroid receptor superfamily. Nature. 1989; 340(6229):163–6. PMid:2739739. Available from: https:// doi.org/10.1038/340163a0

  • Wärnmark A, Treuter E, Wright AP, Gustafsson J. Activation functions 1 and 2 of nuclear receptors: molecular strategies for transcriptional activation. Mol. Endocrinol.2003; 17:10. PMid:12893880. Available from: https://doi.org/10.1210/me.2002-0384

  • Weinberger C, Hollenberg SM, Rosenfeld MG, Evans RM.Domain structure of human glucocorticoid receptor and its relationship to the v-erb-A oncogene product. Nature.1985; 318(6047):670–2. PMid:3841189. Available from: https://doi.org/10.1038/318670a0

  • Weinberger C, Thompson C, Ong E, Gruol D, Evans R. The c-erbA gene encodes a thyroid hormone receptor. Nature.1986; 324:641–6. PMid:2879243. Available from: https:// doi.org/10.1038/324641a0

  • Willy PJ, Umesono K, Ong ES, Evans RM, Heyman RA, Mangelsdorf DJ. LXR, a nuclear receptor that defines a distinct retinoid response pathway. Genes Dev. 1995; 9(9):1033–45. PMid:7744246. Available from: https://doi.org/10.1101/gad.9.9.1033

  • Wong M, Ramayya MS, Chrousos GP, Driggers PH, Parker KL. Cloning and sequence analysis of the human gene encoding steroidogenic factor 1. J Mol Endocrinol. 1996; 17(2):139–47. PMid:8938589. Available from: https://doi.org/10.1677/jme.0.0170139

  • Yamagata K, Furuta H, Oda N, Kaisaki PJ, Menzel S, Cox NJ, Fajans SS, Signorini S, Stoffel M, Bell GI. Mutations in the hepatocyte nuclear factor-4alpha gene in maturity-onset diabetes of the young (MODY1). Nature.1996; 384(6608):458–60. Available from: https://doi.org/10.1038/384458a0

  • Yoshikawa T, Brkanac Z, Dupont BR, Xing GQ, Leach RJ, Detera-Wadleigh SD. Assignment of the human nuclear hormone receptor, NUC1 (PPARD), to chromosome 6p21.1-p21.2. Genomics. 1996; 35(3):637–8.PMid:8812511. Available from: https://doi.org/10.1006/ geno.1996.0417

  • Yoshikawa T, DuPont BR, Leach RJ, Detera-Wadleigh SD. New variants of the human and rat nuclear hormone receptor, TR4: expression and chromosomal localization of the human gene. Genomics. 1996a; 35(2):361–6.PMid:8661150. https://doi.org/10.1006/geno.1996.0368

  • Yu RT, McKeown M, Evans RM, Umesono K. Relationship between Drosophila gap gene tailless and a vertebrate nuclear receptor Tlx. Nature. 1994; 370(6488):375– 9. PMid:8047143. Available from: https://doi.org/10.1038/370375a0

  • Yu VC, Delsert C, Andersen B, Holloway JM, Devary OV, Näär AM, Kim SY, Boutin JM, Glass CK, Rosenfeld MG.RXR beta: A coregulator that enhances binding of retinoic acid, thyroid hormone, and vitamin D receptors to their cognate response elements. Cell. 1991; 67(6):1251–66. Available from: https://doi.org/10.1016/0092-8674(91)90301-E

  • Zanaria E, Muscatelli F, Bardoni B, Strom TM, Guioli S, Guo W, Lalli E, Moser C, Walker AP, McCabe ER, et al. An unusual member of the nuclear hormone receptor superfamily responsible for X-linked adrenal hypoplasia congenita.Nature. 1994; 372(6507):635–41. PMid:7990953. Available from: https://doi.org/10.1038/372635a0

  • Zanger UM, Schwab M. Cytochrome P450 enzymes in drug metabolism: regulation of gene expression, enzyme activities, and impact of genetic variation. Pharmacol Ther.2013; 138:103–41. PMid:23333322. Available from: https:// doi.org/10.1016/j.pharmthera.2012.12.007

  • Zhang Z, Burch PE, Cooney AJ, Lanz RB, Pereira FA, Wu J, Gibbs RA, Weinstock G, Wheeler DA. Genomic analysis of the nuclear receptor family: new insights into structure, regulation, and evolution from the rat genome. Genome Res.2004; 14(4):580–90. PMid:15059999 PMCid:PMC383302.Available from: https://doi.org/10.1101/gr.2160004

  • Zhi X, Zhou XE, Melcher K, Xu HE. Structures and regulation of non-X orphan nuclear receptors: A retinoid hypothesis. J Steroid Biochem Mol Biol. 2016; 157:27–40.PMid:26159912. Available from: https://doi.org/10.1016/j.jsbmb.2015.06.012


Abstract Views: 456

PDF Views: 0




  • A Compendium of Nuclear Receptors:The Superfamily of Ligand-Modulated Transcription Factors

Abstract Views: 456  |  PDF Views: 0

Authors

Amit K. Dash
Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi – 110067, India
Rakesh K. Tyagi
Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi – 110067, India

Abstract


The ‘Nuclear Receptor Super-family’ is a group of ligand-modulated transcription factors with 48 members identified in human genome. Members of this family of receptors are now established to be involved in regulation of a plethora of physiological processes in the paradigms of development, reproduction, metabolism and homeostasis. Also, in the myriads of patho-physiological processes, these receptors have consistently exhibited enormous potential as targets for the treatment of diseases such as cancers, osteoporosis, diabetes, obesity, coronary heart disease, asthma, hypertension, thyroid conditions and multiple other metabolic disorders. In recent times, it is estimated that about 15% of the clinical drugs, used in treatments of different ailments, target nuclear receptors. These receptors include steroid/thyroid hormone receptors and orphan/adopted receptors that function as intra-cellular transcription factors to regulate expression of several hundreds of genes in response to their cognate ligands. Interestingly, nuclear receptors are also being assigned a novel role in serving as ‘epigenetic marks’ for the retention and transmission of cellular ‘transcriptional memory’. These receptors function primarily either as homodimers or heterodimers with Retinoid X Receptor (RXR) or sometimes as monomers. Being ‘drug responsive’ these receptors offer attractive targets for drug discovery since their activities can be favorably modulated by interacting ligands. However, many of the newly discovered members of this family of receptors remain incompletely understood, both in terms of physiological roles and activating ligands. In brief, nuclear receptors represent enormous potential for drug discovery and are continuously being examined to unravel the mysteries underlying their mechanisms of action. It has been well-over three decades since the cloning of steroid/nuclear receptors in the 1980s. Therefore, it’s only appropriate to prepare a comprehensive review that provides a compendium of facts and events from receptor cloning and characterization to establishment of receptor domain structures, physiological functioning and consequences of receptor malfunctioning. This review is expected to serve as a refreshing compendium of nuclear receptors for both, the beginners, as well as experts working in the areas of nuclear receptor biology.

Keywords


Classification, Diseases, Diversity, Drug Targets, Epigenetics, Nuclear Receptors, Transcription Factors, Structure.

References





DOI: https://doi.org/10.18519/jer%2F2016%2Fv20%2F149824