A novel orphan receptor specific for a subset of thyroid hormone-responsive elements and its interaction with the retinoid/thyroid hormone receptor subfamily. (original) (raw)
- Journal List
- Mol Cell Biol
- v.14(10); 1994 Oct
- PMC359232
Mol Cell Biol. 1994 Oct; 14(10): 7025–7035.
La Jolla Cancer Research Foundation, California 92037.
Abstract
The steroid/hormone nuclear receptor superfamily comprises several subfamilies of receptors that interact with overlapping DNA sequences and/or related ligands. The thyroid/retinoid hormone receptor subfamily has recently attracted much interest because of the complex network of its receptor interactions. The retinoid X receptors (RXRs), for instance, play a very central role in this subfamily, forming heterodimers with several receptors. Here we describe a novel member of this subfamily that interacts with RXR. Using a v-erbA probe, we obtained a cDNA which encodes a novel 445-amino-acid protein, RLD-1, that contains the characteristic domains of nuclear receptors. Northern (RNA) blot analysis showed that in mature rats, the receptor is highly expressed in spleen, pituitary, lung, liver, and fat. In addition, weaker expression is observed in several other tissues. Amino acid sequence alignment and DNA-binding data revealed that the DNA-binding domain of the new receptor is related to that of the thyroid/retinoid subgroup of nuclear receptors. RLD-1 preferentially binds as a heterodimer with RXR to a direct repeat of the half-site sequence 5'-G/AGGTCA-3', separated by four nucleotides (DR-4). Surprisingly, this binding is dependent to a high degree on the nature of the spacing nucleotides. None of the known nuclear receptor ligands activated RLD-1. In contrast, a DR-4-dependent constitutive transcriptional activation of a chloramphenicol acetyltransferase reporter gene by the RLD-1/RXR alpha heterodimer was observed. Our data suggest a highly specific role for this novel receptor within the network of gene regulation by the thyroid/retinoid receptor subfamily.
Full text
Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (2.6M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.
Images in this article
Click on the image to see a larger version.
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Amy CM, Williams-Ahlf B, Naggert J, Smith S. Molecular cloning of the mammalian fatty acid synthase gene and identification of the promoter region. Biochem J. 1990 Nov 1;271(3):675–679. [PMC free article] [PubMed] [Google Scholar]
- 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 Mar;14(3):1544–1552. [PMC free article] [PubMed] [Google Scholar]
- Beato M. Gene regulation by steroid hormones. Cell. 1989 Feb 10;56(3):335–344. [PubMed] [Google Scholar]
- Carlberg C, Bendik I, Wyss A, Meier E, Sturzenbecker LJ, Grippo JF, Hunziker W. Two nuclear signalling pathways for vitamin D. Nature. 1993 Feb 18;361(6413):657–660. [PubMed] [Google Scholar]
- Chirgwin JM, Przybyla AE, MacDonald RJ, Rutter WJ. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. [PubMed] [Google Scholar]
- Cooney AJ, Tsai SY, O'Malley BW, Tsai MJ. Chicken ovalbumin upstream promoter transcription factor (COUP-TF) dimers bind to different GGTCA response elements, allowing COUP-TF to repress hormonal induction of the vitamin D3, thyroid hormone, and retinoic acid receptors. Mol Cell Biol. 1992 Sep;12(9):4153–4163. [PMC free article] [PubMed] [Google Scholar]
- Damm K, Heyman RA, Umesono K, Evans RM. Functional inhibition of retinoic acid response by dominant negative retinoic acid receptor mutants. Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):2989–2993. [PMC free article] [PubMed] [Google Scholar]
- Danielian PS, White R, Lees JA, Parker MG. Identification of a conserved region required for hormone dependent transcriptional activation by steroid hormone receptors. EMBO J. 1992 Mar;11(3):1025–1033. [PMC free article] [PubMed] [Google Scholar]
- Davis IJ, Hazel TG, Lau LF. Transcriptional activation by Nur77, a growth factor-inducible member of the steroid hormone receptor superfamily. Mol Endocrinol. 1991 Jun;5(6):854–859. [PubMed] [Google Scholar]
- Debuire B, Henry C, Bernissa M, Biserte G, Claverie JM, Saule S, Martin P, Stehelin D. Sequencing the erbA gene of avian erythroblastosis virus reveals a new type of oncogene. Science. 1984 Jun 29;224(4656):1456–1459. [PubMed] [Google Scholar]
- Disela C, Glineur C, Bugge T, Sap J, Stengl G, Dodgson J, Stunnenberg H, Beug H, Zenke M. v-erbA overexpression is required to extinguish c-erbA function in erythroid cell differentiation and regulation of the erbA target gene CAII. Genes Dev. 1991 Nov;5(11):2033–2047. [PubMed] [Google Scholar]
- Evans RM. The steroid and thyroid hormone receptor superfamily. Science. 1988 May 13;240(4854):889–895. [PMC free article] [PubMed] [Google Scholar]
- Feinberg AP, Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. [PubMed] [Google Scholar]
- Forman BM, Samuels HH. Interactions among a subfamily of nuclear hormone receptors: the regulatory zipper model. Mol Endocrinol. 1990 Sep;4(9):1293–1301. [PubMed] [Google Scholar]
- Forman BM, Yang CR, Au M, Casanova J, Ghysdael J, Samuels HH. 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. [PubMed] [Google Scholar]
- Freedman LP, Arce V, Perez Fernandez R. DNA sequences that act as high affinity targets for the vitamin D3 receptor in the absence of the retinoid X receptor. Mol Endocrinol. 1994 Mar;8(3):265–273. [PubMed] [Google Scholar]
- Graupner G, Wills KN, Tzukerman M, Zhang XK, Pfahl M. Dual regulatory role for thyroid-hormone receptors allows control of retinoic-acid receptor activity. Nature. 1989 Aug 24;340(6235):653–656. [PubMed] [Google Scholar]
- Green S, Chambon P. Nuclear receptors enhance our understanding of transcription regulation. Trends Genet. 1988 Nov;4(11):309–314. [PubMed] [Google Scholar]
- Hazel TG, Misra R, Davis IJ, Greenberg ME, Lau LF. Nur77 is differentially modified in PC12 cells upon membrane depolarization and growth factor treatment. Mol Cell Biol. 1991 Jun;11(6):3239–3246. [PMC free article] [PubMed] [Google Scholar]
- Hermann T, Hoffmann B, Piedrafita FJ, Zhang XK, Pfahl M. V-erbA requires auxiliary proteins for dominant negative activity. Oncogene. 1993 Jan;8(1):55–65. [PubMed] [Google Scholar]
- Hermann T, Hoffmann B, Zhang XK, Tran P, Pfahl M. Heterodimeric receptor complexes determine 3,5,3'-triiodothyronine and retinoid signaling specificities. Mol Endocrinol. 1992 Jul;6(7):1153–1162. [PubMed] [Google Scholar]
- Hermann T, Zhang XK, Tzukerman M, Wills KN, Graupner G, Pfahl M. Regulatory functions of a non-ligand-binding thyroid hormone receptor isoform. Cell Regul. 1991 Jul;2(7):565–574. [PMC free article] [PubMed] [Google Scholar]
- Hoffmann B, Lehmann JM, Zhang XK, Hermann T, Husmann M, Graupner G, Pfahl M. A retinoic acid receptor-specific element controls the retinoic acid receptor-beta promoter. Mol Endocrinol. 1990 Nov;4(11):1727–1736. [PubMed] [Google Scholar]
- Huggenvik JI, Collard MW, Kim YW, Sharma RP. Modification of the retinoic acid signaling pathway by the catalytic subunit of protein kinase-A. Mol Endocrinol. 1993 Apr;7(4):543–550. [PubMed] [Google Scholar]
- Hunt CR, Ro JH, Dobson DE, Min HY, Spiegelman BM. Adipocyte P2 gene: developmental expression and homology of 5'-flanking sequences among fat cell-specific genes. Proc Natl Acad Sci U S A. 1986 Jun;83(11):3786–3790. [PMC free article] [PubMed] [Google Scholar]
- Hwung YP, Crowe DT, Wang LH, Tsai SY, Tsai MJ. The COUP transcription factor binds to an upstream promoter element of the rat insulin II gene. Mol Cell Biol. 1988 May;8(5):2070–2077. [PMC free article] [PubMed] [Google Scholar]
- Jurutka PW, Hsieh JC, MacDonald PN, Terpening CM, Haussler CA, Haussler MR, Whitfield GK. Phosphorylation of serine 208 in the human vitamin D receptor. The predominant amino acid phosphorylated by casein kinase II, in vitro, and identification as a significant phosphorylation site in intact cells. J Biol Chem. 1993 Mar 25;268(9):6791–6799. [PubMed] [Google Scholar]
- Kurokawa R, Yu VC, När A, Kyakumoto S, Han Z, Silverman S, Rosenfeld MG, Glass CK. 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. [PubMed] [Google Scholar]
- Kim HS, Crone DE, Sprung CN, Tillman JB, Force WR, Crew MD, Mote PL, Spindler SR. Positive and negative thyroid hormone response elements are composed of strong and weak half-sites 10 nucleotides in length. Mol Endocrinol. 1992 Sep;6(9):1489–1501. [PubMed] [Google Scholar]
- Kimura A, Nishiyori A, Murakami T, Tsukamoto T, Hata S, Osumi T, Okamura R, Mori M, Takiguchi M. Chicken ovalbumin upstream promoter-transcription factor (COUP-TF) represses transcription from the promoter of the gene for ornithine transcarbamylase in a manner antagonistic to hepatocyte nuclear factor-4 (HNF-4). J Biol Chem. 1993 May 25;268(15):11125–11133. [PubMed] [Google Scholar]
- Kliewer SA, Umesono K, Heyman RA, Mangelsdorf DJ, Dyck JA, Evans RM. Retinoid X receptor-COUP-TF interactions modulate retinoic acid signaling. Proc Natl Acad Sci U S A. 1992 Feb 15;89(4):1448–1452. [PMC free article] [PubMed] [Google Scholar]
- Kliewer SA, Umesono K, Mangelsdorf DJ, Evans RM. Retinoid X receptor interacts with nuclear receptors in retinoic acid, thyroid hormone and vitamin D3 signalling. Nature. 1992 Jan 30;355(6359):446–449. [PMC free article] [PubMed] [Google Scholar]
- Laudet V, Hänni C, Coll J, Catzeflis F, Stéhelin D. Evolution of the nuclear receptor gene superfamily. EMBO J. 1992 Mar;11(3):1003–1013. [PMC free article] [PubMed] [Google Scholar]
- Lazar MA, Hodin RA, Darling DS, Chin WW. 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. [PubMed] [Google Scholar]
- 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-erbA alpha transcriptional unit. Mol Cell Biol. 1989 Mar;9(3):1128–1136. [PMC free article] [PubMed] [Google Scholar]
- Lee MO, Hobbs PD, Zhang XK, Dawson MI, 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. [PMC free article] [PubMed] [Google Scholar]
- Lehmann JM, Jong L, Fanjul A, Cameron JF, Lu XP, Haefner P, Dawson MI, Pfahl M. Retinoids selective for retinoid X receptor response pathways. Science. 1992 Dec 18;258(5090):1944–1946. [PubMed] [Google Scholar]
- Lehmann JM, Zhang XK, Graupner G, Lee MO, 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. [PMC free article] [PubMed] [Google Scholar]
- 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 Jan 24;68(2):377–395. [PubMed] [Google Scholar]
- Luckow B, Schütz G. Cell-type specificity of regulatory elements identified by linker scanning mutagenesis in the promoter of the chicken lysozyme gene. Nucleic Acids Res. 1989 Nov 11;17(21):8451–8462. [PMC free article] [PubMed] [Google Scholar]
- Mader S, Chen JY, 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. [PMC free article] [PubMed] [Google Scholar]
- Mader S, Leroy P, Chen JY, Chambon P. Multiple parameters control the selectivity of nuclear receptors for their response elements. Selectivity and promiscuity in response element recognition by retinoic acid receptors and retinoid X receptors. J Biol Chem. 1993 Jan 5;268(1):591–600. [PubMed] [Google Scholar]
- MacDonald PN, Dowd DR, Nakajima S, Galligan MA, Reeder MC, Haussler CA, Ozato K, Haussler MR. Retinoid X receptors stimulate and 9-cis retinoic acid inhibits 1,25-dihydroxyvitamin D3-activated expression of the rat osteocalcin gene. Mol Cell Biol. 1993 Sep;13(9):5907–5917. [PMC free article] [PubMed] [Google Scholar]
- O'Malley BW, Conneely OM. Orphan receptors: in search of a unifying hypothesis for activation. Mol Endocrinol. 1992 Sep;6(9):1359–1361. [PubMed] [Google Scholar]
- Paulsen RE, Weaver CA, Fahrner TJ, Milbrandt J. Domains regulating transcriptional activity of the inducible orphan receptor NGFI-B. J Biol Chem. 1992 Aug 15;267(23):16491–16496. [PubMed] [Google Scholar]
- Pfahl M. Nuclear receptor/AP-1 interaction. Endocr Rev. 1993 Oct;14(5):651–658. [PubMed] [Google Scholar]
- Pfahl M, Apfel R, Bendik I, Fanjul A, Graupner G, Lee MO, La-Vista N, Lu XP, Piedrafita J, Ortiz MA, et al. Nuclear retinoid receptors and their mechanism of action. Vitam Horm. 1994;49:327–382. [PubMed] [Google Scholar]
- Pfahl M, Tzukerman M, Zhang XK, Lehmann JM, Hermann T, Wills KN, Graupner G. Nuclear retinoic acid receptors: cloning, analysis, and function. Methods Enzymol. 1990;189:256–270. [PubMed] [Google Scholar]
- Segraves WA, Hogness DS. The E75 ecdysone-inducible gene responsible for the 75B early puff in Drosophila encodes two new members of the steroid receptor superfamily. Genes Dev. 1990 Feb;4(2):204–219. [PubMed] [Google Scholar]
- Sladek FM, Zhong WM, Lai E, Darnell JE., Jr Liver-enriched transcription factor HNF-4 is a novel member of the steroid hormone receptor superfamily. Genes Dev. 1990 Dec;4(12B):2353–2365. [PubMed] [Google Scholar]
- Takimoto GS, Tasset DM, Eppert AC, Horwitz KB. Hormone-induced progesterone receptor phosphorylation consists of sequential DNA-independent and DNA-dependent stages: analysis with zinc finger mutants and the progesterone antagonist ZK98299. Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):3050–3054. [PMC free article] [PubMed] [Google Scholar]
- Tran P, Zhang XK, Salbert G, Hermann T, Lehmann JM, Pfahl M. COUP orphan receptors are negative regulators of retinoic acid response pathways. Mol Cell Biol. 1992 Oct;12(10):4666–4676. [PMC free article] [PubMed] [Google Scholar]
- Thomas HE, Stunnenberg HG, Stewart AF. Heterodimerization of the Drosophila ecdysone receptor with retinoid X receptor and ultraspiracle. Nature. 1993 Apr 1;362(6419):471–475. [PubMed] [Google Scholar]
- Umesono K, Murakami KK, Thompson CC, Evans RM. Direct repeats as selective response elements for the thyroid hormone, retinoic acid, and vitamin D3 receptors. Cell. 1991 Jun 28;65(7):1255–1266. [PMC free article] [PubMed] [Google Scholar]
- Wang LH, Tsai SY, Sagami I, Tsai MJ, O'Malley BW. Purification and characterization of chicken ovalbumin upstream promoter transcription factor from HeLa cells. J Biol Chem. 1987 Nov 25;262(33):16080–16086. [PubMed] [Google Scholar]
- Wilson TE, Fahrner TJ, Johnston M, Milbrandt J. Identification of the DNA binding site for NGFI-B by genetic selection in yeast. Science. 1991 May 31;252(5010):1296–1300. [PubMed] [Google Scholar]
- Yu VC, Delsert C, Andersen B, Holloway JM, Devary OV, När 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 Dec 20;67(6):1251–1266. [PubMed] [Google Scholar]
- Zenke M, Muñoz A, Sap J, Vennström B, Beug H. v-erbA oncogene activation entails the loss of hormone-dependent regulator activity of c-erbA. Cell. 1990 Jun 15;61(6):1035–1049. [PubMed] [Google Scholar]
- Zhang XK, Hoffmann B, Tran PB, 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. [PubMed] [Google Scholar]
- Zhang XK, Lehmann J, Hoffmann B, Dawson MI, 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. [PubMed] [Google Scholar]
- Zhang XK, Tran PB, Pfahl M. DNA binding and dimerization determinants for thyroid hormone receptor alpha and its interaction with a nuclear protein. Mol Endocrinol. 1991 Dec;5(12):1909–1920. [PubMed] [Google Scholar]
- Zhang XK, Wills KN, Graupner G, Tzukerman M, Hermann T, Pfahl M. Ligand-binding domain of thyroid hormone receptors modulates DNA binding and determines their bifunctional roles. New Biol. 1991 Feb;3(2):169–181. [PubMed] [Google Scholar]
Articles from Molecular and Cellular Biology are provided here courtesy of Taylor & Francis