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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1988 May;85(10):3294–3298. doi: 10.1073/pnas.85.10.3294

Cloning and expression of full-length cDNA encoding human vitamin D receptor.

A R Baker 1, D P McDonnell 1, M Hughes 1, T M Crisp 1, D J Mangelsdorf 1, M R Haussler 1, J W Pike 1, J Shine 1, B W O'Malley 1
PMCID: PMC280195  PMID: 2835767

Abstract

Complementary DNA clones encoding the human vitamin D receptor have been isolated from human intestine and T47D cell cDNA libraries. The nucleotide sequence of the 4605-base pair (bp) cDNA includes a noncoding leader sequence of 115 bp, a 1281-bp open reading frame, and 3209 bp of 3' noncoding sequence. Two polyadenylylation signals, AATAAA, are present 25 and 70 bp upstream of the poly(A) tail, respectively. RNA blot hybridization indicates a single mRNA species of approximately equal to 4600 bp. Transfection of the cloned sequences into COS-1 cells results in the production of a single receptor species indistinguishable from the native receptor. Sequence comparisons demonstrate that the vitamin D receptor belongs to the steroid-receptor gene family and is closest in size and sequence to another member of this family, the thyroid hormone receptor.

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Selected References

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  1. Aviv H., Leder P. Purification of biologically active globin messenger RNA by chromatography on oligothymidylic acid-cellulose. Proc Natl Acad Sci U S A. 1972 Jun;69(6):1408–1412. doi: 10.1073/pnas.69.6.1408. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  3. Deans R. J., Denis K. A., Taylor A., Wall R. Expression of an immunoglobulin heavy chain gene transfected into lymphocytes. Proc Natl Acad Sci U S A. 1984 Mar;81(5):1292–1296. doi: 10.1073/pnas.81.5.1292. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Denhardt D. T. A membrane-filter technique for the detection of complementary DNA. Biochem Biophys Res Commun. 1966 Jun 13;23(5):641–646. doi: 10.1016/0006-291x(66)90447-5. [DOI] [PubMed] [Google Scholar]
  5. Freake H. C., Marcocci C., Iwasaki J., MacIntyre I. 1,25-dihydroxyvitamin D3 specifically binds to a human breast cancer cell line (T47D) and stimulates growth. Biochem Biophys Res Commun. 1981 Aug 31;101(4):1131–1138. doi: 10.1016/0006-291x(81)91565-5. [DOI] [PubMed] [Google Scholar]
  6. Giguère V., Hollenberg S. M., Rosenfeld M. G., Evans R. M. Functional domains of the human glucocorticoid receptor. Cell. 1986 Aug 29;46(5):645–652. doi: 10.1016/0092-8674(86)90339-9. [DOI] [PubMed] [Google Scholar]
  7. Green S., Walter P., Kumar V., Krust A., Bornert J. M., Argos P., Chambon P. Human oestrogen receptor cDNA: sequence, expression and homology to v-erb-A. Nature. 1986 Mar 13;320(6058):134–139. doi: 10.1038/320134a0. [DOI] [PubMed] [Google Scholar]
  8. Greene G. L., Gilna P., Waterfield M., Baker A., Hort Y., Shine J. Sequence and expression of human estrogen receptor complementary DNA. Science. 1986 Mar 7;231(4742):1150–1154. doi: 10.1126/science.3753802. [DOI] [PubMed] [Google Scholar]
  9. Haussler M. R., McCain T. A. Basic and clinical concepts related to vitamin D metabolism and action (second of two parts). N Engl J Med. 1977 Nov 10;297(19):1041–1050. doi: 10.1056/NEJM197711102971906. [DOI] [PubMed] [Google Scholar]
  10. Haussler M. R. Vitamin D receptors: nature and function. Annu Rev Nutr. 1986;6:527–562. doi: 10.1146/annurev.nu.06.070186.002523. [DOI] [PubMed] [Google Scholar]
  11. Hollenberg S. M., Weinberger C., Ong E. S., Cerelli G., Oro A., Lebo R., Thompson E. B., Rosenfeld M. G., Evans R. M. Primary structure and expression of a functional human glucocorticoid receptor cDNA. Nature. 1985 Dec 19;318(6047):635–641. doi: 10.1038/318635a0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kozak M. Compilation and analysis of sequences upstream from the translational start site in eukaryotic mRNAs. Nucleic Acids Res. 1984 Jan 25;12(2):857–872. doi: 10.1093/nar/12.2.857. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kumar V., Green S., Staub A., Chambon P. Localisation of the oestradiol-binding and putative DNA-binding domains of the human oestrogen receptor. EMBO J. 1986 Sep;5(9):2231–2236. doi: 10.1002/j.1460-2075.1986.tb04489.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Mangelsdorf D. J., Koeffler H. P., Donaldson C. A., Pike J. W., Haussler M. R. 1,25-Dihydroxyvitamin D3-induced differentiation in a human promyelocytic leukemia cell line (HL-60): receptor-mediated maturation to macrophage-like cells. J Cell Biol. 1984 Feb;98(2):391–398. doi: 10.1083/jcb.98.2.391. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Mangelsdorf D. J., Pike J. W., Haussler M. R. Avian and mammalian receptors for 1,25-dihydroxyvitamin D3: in vitro translation to characterize size and hormone-dependent regulation. Proc Natl Acad Sci U S A. 1987 Jan;84(2):354–358. doi: 10.1073/pnas.84.2.354. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Marx S. J., Liberman U. A., Eil C., Gamblin G. T., DeGrange D. A., Balsan S. Hereditary resistance to 1,25-dihydroxyvitamin D. Recent Prog Horm Res. 1984;40:589–620. doi: 10.1016/b978-0-12-571140-1.50019-0. [DOI] [PubMed] [Google Scholar]
  17. McDonnell D. P., Mangelsdorf D. J., Pike J. W., Haussler M. R., O'Malley B. W. Molecular cloning of complementary DNA encoding the avian receptor for vitamin D. Science. 1987 Mar 6;235(4793):1214–1217. doi: 10.1126/science.3029866. [DOI] [PubMed] [Google Scholar]
  18. Miesfeld R., Rusconi S., Godowski P. J., Maler B. A., Okret S., Wikström A. C., Gustafsson J. A., Yamamoto K. R. Genetic complementation of a glucocorticoid receptor deficiency by expression of cloned receptor cDNA. Cell. 1986 Aug 1;46(3):389–399. doi: 10.1016/0092-8674(86)90659-8. [DOI] [PubMed] [Google Scholar]
  19. Miller J., McLachlan A. D., Klug A. Repetitive zinc-binding domains in the protein transcription factor IIIA from Xenopus oocytes. EMBO J. 1985 Jun;4(6):1609–1614. doi: 10.1002/j.1460-2075.1985.tb03825.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. 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 Res Commun. 1987 Mar 13;143(2):740–748. doi: 10.1016/0006-291x(87)91416-1. [DOI] [PubMed] [Google Scholar]
  21. Okayama H., Berg P. High-efficiency cloning of full-length cDNA. Mol Cell Biol. 1982 Feb;2(2):161–170. doi: 10.1128/mcb.2.2.161. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Pike J. W., Haussler M. R. Association of 1,25-dihydroxyvitamin D3 with cultured 3T6 mouse fibroblasts. Cellular uptake and receptor-mediated migration to the nucleus. J Biol Chem. 1983 Jul 25;258(14):8554–8560. [PubMed] [Google Scholar]
  23. Pike J. W. Intracellular receptors mediate the biologic action of 1,25-dihydroxyvitamin D3. Nutr Rev. 1985 Jun;43(6):161–168. doi: 10.1111/j.1753-4887.1985.tb02406.x. [DOI] [PubMed] [Google Scholar]
  24. Pike J. W., Sleator N. M. Hormone-dependent phosphorylation of the 1,25-dihydroxyvitamin D3 receptor in mouse fibroblasts. Biochem Biophys Res Commun. 1985 Aug 30;131(1):378–385. doi: 10.1016/0006-291x(85)91813-3. [DOI] [PubMed] [Google Scholar]
  25. Putkey J. A., Wecksler W. R., Norman A. W. The interaction of 1,25-dihydroxyvitamin D3 with its intestinal mucosa receptor: kinetic parameters and structural requirements. Lipids. 1978 Oct;13(10):723–729. doi: 10.1007/BF02533752. [DOI] [PubMed] [Google Scholar]
  26. Rigby P. W., Dieckmann M., Rhodes C., Berg P. Labeling deoxyribonucleic acid to high specific activity in vitro by nick translation with DNA polymerase I. J Mol Biol. 1977 Jun 15;113(1):237–251. doi: 10.1016/0022-2836(77)90052-3. [DOI] [PubMed] [Google Scholar]
  27. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Wecksler W. R., Norman A. W. An hydroxylapatite batch assay for the quantitation of 1alpha,25-dihydroxyvitamin D3-receptor complexes. Anal Biochem. 1979 Jan 15;92(2):314–323. doi: 10.1016/0003-2697(79)90664-x. [DOI] [PubMed] [Google Scholar]
  29. Weinberger C., Hollenberg S. M., Rosenfeld M. G., Evans R. M. Domain structure of human glucocorticoid receptor and its relationship to the v-erb-A oncogene product. Nature. 1985 Dec 19;318(6047):670–672. doi: 10.1038/318670a0. [DOI] [PubMed] [Google Scholar]
  30. Weinberger C., Thompson C. C., Ong E. S., Lebo R., Gruol D. J., Evans R. M. The c-erb-A gene encodes a thyroid hormone receptor. Nature. 1986 Dec 18;324(6098):641–646. doi: 10.1038/324641a0. [DOI] [PubMed] [Google Scholar]
  31. Wong G. G., Witek J. S., Temple P. A., Wilkens K. M., Leary A. C., Luxenberg D. P., Jones S. S., Brown E. L., Kay R. M., Orr E. C. Human GM-CSF: molecular cloning of the complementary DNA and purification of the natural and recombinant proteins. Science. 1985 May 17;228(4701):810–815. doi: 10.1126/science.3923623. [DOI] [PubMed] [Google Scholar]
  32. Yamamoto K. R. Steroid receptor regulated transcription of specific genes and gene networks. Annu Rev Genet. 1985;19:209–252. doi: 10.1146/annurev.ge.19.120185.001233. [DOI] [PubMed] [Google Scholar]

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