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PMID: 8114692 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

A new orphan member of the nuclear hormone receptor superfamily that interacts with a subset of retinoic acid response elements.

Molecular and cellular biology ·Vol. 14 ·No. 3 ·1994-03-00 ·Pages 1544-52

Baes M, Gulick T, Choi HS, Martinoli MG, Simha D, Moore DD

Abstract

We have identified and characterized a new orphan member of the nuclear hormone receptor superfamily, called MB67, which is predominantly expressed in liver. MB67 binds and transactivates the retinoic acid response elements that control expression of the retinoic acid receptor beta 2 and alcohol dehydrogenase 3 genes, both of which consist of a direct repeat hexamers related to the consensus AGGTCA, separated by 5 bp. MB67 binds these elements as a heterodimer with the 9-cis-retinoic acid receptor, RXR. However, MB67 does not bind or activate other retinoic acid response elements with alternative hexamer arrangements or any of several other wild-type and synthetic hormone response elements examined. The transactivation of retinoic acid response elements by MB67 is weaker than that conferred by the retinoic acid receptors but does not require the presence of all-trans retinoic acid, 9-cis-retinoic acid, or any exogenously added ligand. We propose that MB67 plays an important role in the complex network of proteins that govern response to retinoic acid and its metabolites.

Related Genes
MB67
MeSH Terms
Amino Acid Sequence Base Sequence Cloning, Molecular Constitutive Androstane Receptor DNA Primers/chemistry DNA, Complementary/genetics DNA-Binding Proteins/genetics Gene Expression Regulation Humans Molecular Sequence Data Receptors, Cytoplasmic and Nuclear/genetics Receptors, Retinoic Acid/genetics Regulatory Sequences, Nucleic Acid Sequence Homology, Amino Acid Trans-Activators/genetics Transcription Factors/genetics
Chemicals
Constitutive Androstane Receptor DNA Primers DNA, Complementary DNA-Binding Proteins Receptors, Cytoplasmic and Nuclear Receptors, Retinoic Acid Trans-Activators Transcription Factors
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Baes M
Department of Molecular Biology, Massachusetts General Hospital, Boston 02114.
Gulick T
Choi H S
Martinoli M G
Simha D
Moore D D
References (71)
71 references, click to expand
  1. Differential capacity of wild type promoter elements for binding and trans-activation by retinoic acid and thyroid hormone receptors.
    Mol Endocrinol. 1992 Oct;6(10):1527-37 PMID: 1333048
  2. Differential modes of activation define orphan subclasses within the steroid/thyroid receptor superfamily.
    Gene Expr. 1992;2(3):273-83 PMID: 1450665
  3. Multiplicity generates diversity in the retinoic acid signalling pathways.
    Trends Biochem Sci. 1992 Oct;17(10):427-33 PMID: 1333659
  4. Thyroid hormone aporeceptor represses T3-inducible promoters and blocks activity of the retinoic acid receptor.
    New Biol. 1989 Dec;1(3):329-36 PMID: 2562125
  5. Liver-enriched transcription factor HNF-4 is a novel member of the steroid hormone receptor superfamily.
    Genes Dev. 1990 Dec;4(12B):2353-65 PMID: 2279702
  6. Retinoic acid response element in the human alcohol dehydrogenase gene ADH3: implications for regulation of retinoic acid synthesis.
    Mol Cell Biol. 1991 Mar;11(3):1638-46 PMID: 1996113
  7. The late retinoic acid induction of laminin B1 gene transcription involves RAR binding to the responsive element.
    EMBO J. 1991 May;10(5):1149-58 PMID: 1850696
  8. Normal development and growth of mice carrying a targeted disruption of the alpha 1 retinoic acid receptor gene.
    Proc Natl Acad Sci U S A. 1993 Feb 15;90(4):1590-4 PMID: 7679509
  9. 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 PMID: 8436299
  10. Function of retinoic acid receptor gamma in the mouse.
    Cell. 1993 May 21;73(4):643-58 PMID: 8388780
  11. Hepatocyte nuclear factor-4 activates medium chain acyl-CoA dehydrogenase gene transcription by interacting with a complex regulatory element.
    J Biol Chem. 1993 Jul 5;268(19):13805-10 PMID: 8314750
  12. High postnatal lethality and testis degeneration in retinoic acid receptor alpha mutant mice.
    Proc Natl Acad Sci U S A. 1993 Aug 1;90(15):7225-9 PMID: 8394014
  13. Steroidogenic factor 1, an orphan nuclear receptor, regulates the expression of the rat aromatase gene in gonadal tissues.
    Mol Endocrinol. 1993 Jun;7(6):776-86 PMID: 8395654
  14. Differentially expressed isoforms of the mouse retinoic acid receptor beta generated by usage of two promoters and alternative splicing.
    EMBO J. 1991 Jan;10(1):71-81 PMID: 1846599
  15. Three amino acids of the oestrogen receptor are essential to its ability to distinguish an oestrogen from a glucocorticoid-responsive element.
    Nature. 1989 Mar 16;338(6212):271-4 PMID: 2922054
  16. Identification of a thyroid hormone receptor that is pituitary-specific.
    Science. 1989 Apr 7;244(4900):76-9 PMID: 2539642
  17. Trans-activation by thyroid hormone receptors: functional parallels with steroid hormone receptors.
    Proc Natl Acad Sci U S A. 1989 May;86(10):3494-8 PMID: 2726731
  18. Two amino acids within the knuckle of the first zinc finger specify DNA response element activation by the glucocorticoid receptor.
    Cell. 1989 Jun 30;57(7):1131-8 PMID: 2500250
  19. Determinants of target gene specificity for steroid/thyroid hormone receptors.
    Cell. 1989 Jun 30;57(7):1139-46 PMID: 2500251
  20. Repression of transcription mediated at a thyroid hormone response element by the v-erb-A oncogene product.
    Nature. 1989 Jul 20;340(6230):242-4 PMID: 2569164
  21. Dual regulatory role for thyroid-hormone receptors allows control of retinoic-acid receptor activity.
    Nature. 1989 Aug 24;340(6235):653-6 PMID: 2549424
  22. Identification of a retinoic acid responsive element in the retinoic acid receptor beta gene.
    Nature. 1990 Jan 11;343(6254):177-80 PMID: 2153268
  23. 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 PMID: 2628734
  24. 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):204-19 PMID: 2110921
  25. 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):5392-6 PMID: 2164682
  26. Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators.
    Nature. 1990 Oct 18;347(6294):645-50 PMID: 2129546
  27. Multiple isoforms of the mouse retinoic acid receptor alpha are generated by alternative splicing and differential induction by retinoic acid.
    EMBO J. 1991 Jan;10(1):59-69 PMID: 1846598
  28. Thyroid hormone regulation of gene expression.
    Annu Rev Physiol. 1991;53:17-35 PMID: 2042958
  29. Dopamine activation of an orphan of the steroid receptor superfamily.
    Science. 1991 Jun 14;252(5012):1546-8 PMID: 2047861
  30. Direct repeats as selective response elements for the thyroid hormone, retinoic acid, and vitamin D3 receptors.
    Cell. 1991 Jun 28;65(7):1255-66 PMID: 1648450
  31. The orientation and spacing of core DNA-binding motifs dictate selective transcriptional responses to three nuclear receptors.
    Cell. 1991 Jun 28;65(7):1267-79 PMID: 1648451
  32. A retinoic acid response element is present in the mouse cellular retinol binding protein I (mCRBPI) promoter.
    EMBO J. 1991 Aug;10(8):2223-30 PMID: 1648481
  33. 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):555-61 PMID: 1651173
  34. Expression of a retinoic acid response element-hsplacZ transgene defines specific domains of transcriptional activity during mouse embryogenesis.
    Genes Dev. 1991 Aug;5(8):1333-44 PMID: 1907940
  35. Retinoic acid affects the expression of nuclear retinoic acid receptors in tissues of retinol-deficient rats.
    Proc Natl Acad Sci U S A. 1991 Sep 15;88(18):8272-6 PMID: 1654565
  36. Transcriptional activation by Nur77, a growth factor-inducible member of the steroid hormone receptor superfamily.
    Mol Endocrinol. 1991 Jun;5(6):854-9 PMID: 1922099
  37. Identification of the DNA binding site for NGFI-B by genetic selection in yeast.
    Science. 1991 May 31;252(5010):1296-300 PMID: 1925541
  38. Functional characterization of a natural retinoic acid responsive element.
    EMBO J. 1991 Dec;10(12):3829-38 PMID: 1657595
  39. Mouse retinoic acid receptor alpha 2 isoform is transcribed from a promoter that contains a retinoic acid response element.
    Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):10138-42 PMID: 1658797
  40. Dopaminergic and ligand-independent activation of steroid hormone receptors.
    Science. 1991 Dec 13;254(5038):1636-9 PMID: 1749936
  41. A quick procedure for purification of functional recombinant proteins over-expressed in E.coli.
    Nucleic Acids Res. 1991 Dec 11;19(23):6650 PMID: 1754408
  42. 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):1251-66 PMID: 1662118
  43. 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):377-95 PMID: 1310259
  44. Retinoid X receptor is an auxiliary protein for thyroid hormone and retinoic acid receptors.
    Nature. 1992 Jan 30;355(6359):441-6 PMID: 1310350
  45. Retinoid X receptor interacts with nuclear receptors in retinoic acid, thyroid hormone and vitamin D3 signalling.
    Nature. 1992 Jan 30;355(6359):446-9 PMID: 1310351
  46. Isolation of monoclonal antibodies specific for human c-myc proto-oncogene product.
    Mol Cell Biol. 1985 Dec;5(12):3610-6 PMID: 3915782
  47. CAT vectors for analysis of eukaryotic promoters and enhancers.
    Gene. 1986;45(1):107-11 PMID: 3023200
  48. Human growth hormone as a reporter gene in regulation studies employing transient gene expression.
    Mol Cell Biol. 1986 Sep;6(9):3173-9 PMID: 3023965
  49. Oestradiol induction of a glucocorticoid-responsive gene by a chimaeric receptor.
    Nature. 1987 Jan 1-7;325(6099):75-8 PMID: 3025750
  50. An LFA-3 cDNA encodes a phospholipid-linked membrane protein homologous to its receptor CD2.
    Nature. 1987 Oct 29-Nov 4;329(6142):840-2 PMID: 3313052
  51. At least six nucleotides preceding the AUG initiator codon enhance translation in mammalian cells.
    J Mol Biol. 1987 Aug 20;196(4):947-50 PMID: 3681984
  52. Identification of a receptor for the morphogen retinoic acid.
    Nature. 1987 Dec 17-23;330(6149):624-9 PMID: 2825036
  53. The steroid and thyroid hormone receptor superfamily.
    Science. 1988 May 13;240(4854):889-95 PMID: 3283939
  54. Functional characterization of the rat growth hormone promoter elements required for induction by thyroid hormone with and without a co-transfected beta type thyroid hormone receptor.
    J Biol Chem. 1989 Jan 5;264(1):178-82 PMID: 2909514
  55. Gene regulation by steroid hormones.
    Cell. 1989 Feb 10;56(3):335-44 PMID: 2644044
  56. The origin of nuclear receptor proteins: a single precursor distinct from other transcription factors.
    Mol Endocrinol. 1992 Jan;6(1):3-7 PMID: 1738368
  57. The mouse peroxisome proliferator activated receptor recognizes a response element in the 5' flanking sequence of the rat acyl CoA oxidase gene.
    EMBO J. 1992 Feb;11(2):433-9 PMID: 1537328
  58. Evolution of the nuclear receptor gene superfamily.
    EMBO J. 1992 Mar;11(3):1003-13 PMID: 1312460
  59. Identification of a conserved region required for hormone dependent transcriptional activation by steroid hormone receptors.
    EMBO J. 1992 Mar;11(3):1025-33 PMID: 1372244
  60. RXR alpha, a promiscuous partner of retinoic acid and thyroid hormone receptors.
    EMBO J. 1992 Apr;11(4):1409-18 PMID: 1314167
  61. 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):1419-35 PMID: 1314168
  62. Transgenic indicator mice for studying activated retinoic acid receptors during development.
    Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3347-51 PMID: 1314386
  63. Characterization of 1,25-dihydroxyvitamin D3 receptor interactions with target sequences in the rat osteocalcin gene.
    Mol Endocrinol. 1992 Apr;6(4):557-62 PMID: 1316548
  64. Heterodimerization of thyroid hormone (TH) receptor with H-2RIIBP (RXR beta) enhances DNA binding and TH-dependent transcriptional activation.
    Proc Natl Acad Sci U S A. 1992 Jun 15;89(12):5572-6 PMID: 1608968
  65. RAR gamma 2 expression is regulated through a retinoic acid response element embedded in Sp1 sites.
    Mol Cell Biol. 1992 Jul;12(7):2976-85 PMID: 1320193
  66. Transcriptional regulation of human apolipoprotein genes ApoB, ApoCIII, and ApoAII by members of the steroid hormone receptor superfamily HNF-4, ARP-1, EAR-2, and EAR-3.
    J Biol Chem. 1992 Aug 5;267(22):15849-60 PMID: 1639815
  67. Domains regulating transcriptional activity of the inducible orphan receptor NGFI-B.
    J Biol Chem. 1992 Aug 15;267(23):16491-6 PMID: 1644831
  68. Homodimer formation of retinoid X receptor induced by 9-cis retinoic acid.
    Nature. 1992 Aug 13;358(6387):587-91 PMID: 1323763
  69. All-trans and 9-cis retinoic acid induction of CRABPII transcription is mediated by RAR-RXR heterodimers bound to DR1 and DR2 repeated motifs.
    Cell. 1992 Oct 2;71(1):73-85 PMID: 1327537
  70. Identification of a novel retinoid-responsive element in the promoter region of the medium chain acyl-coenzyme A dehydrogenase gene.
    J Biol Chem. 1992 Oct 5;267(28):20264-9 PMID: 1328196
  71. Steroidogenic factor I, a key regulator of steroidogenic enzyme expression, is the mouse homolog of fushi tarazu-factor I.
    Mol Endocrinol. 1992 Aug;6(8):1249-58 PMID: 1406703
Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/mcb.14.3.1544-1552.1994
Published
1994-03-00
Pages
1544-52
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC358513
Subset
IM
Grants
NIDDK NIH HHS · R01DK43382 · United States
Databases
GENBANK
Z30425
External Links
PubMed source DOI: 10.1128/mcb.14.3.1544-1552.1994 PMC Full Text View journal details
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