Abstract
THE dihydroxylated form of vitamin D3 (l,25-dihydroxy-D3) mediates a biological response by binding to intracellular receptors1–4 which belong to the steroid receptor superfamily5. These receptors act as ligand-dependent transcription factors that bind to specific DNA sequences (reviewed in refs 6–9). We have identified two classes of vitamin D response elements that are activated either by the vitamin D receptor (VDR) alone or by heterodimers of VDR and the retinoid-X receptor-α (RXR-α)10. The motif GGGTGA arranged as a direct repeat with a spacing of six nucleotides or as a palindrome without spacing, or as an inverted palindrome with a 12-nucleotide spacing, confers vitamin D inducibility mediated by VDR alone. A second class of response elements, composed of directly repeated pairs of motifs (GGTCCA, AGGTCA, or GGGTGA) spaced by three nucleotides, is synergistically activated by RXR and VDR, but only in the presence of both ligands. Thus, the RXR ligand and the nature of the response element determine whether a nuclear receptor is co-regulated by RXR.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Minghetti, P. P. & Norman, A. W. FASEB J. 2, 3043–3053 (1988).
Pike, J. W. A. Rev. Nutr. 11, 189–216 (1991).
DeLuca, H. F., Krisinger, J. & Darwish, H. Kidney Int. 38, S2–S8 (1990).
Haussler, M. R. et al. Recent prog. Horm. Res. 44, 263–297 (1988).
Baker, A. R. et al. Proc. natn. Acad. Sci. U.S.A. 85, 3294–3298 (1988).
Green, S. & Chambon, P. Trends Genet. 4, 309–314 (1988).
Evans, R. M. Science 240, 889–895 (1988).
Beato, M. Cell 56, 335–344 (1989).
O'Malley, B. W. Molec. Endocr. 4, 363–369 (1990).
Mangelsdorf, D. J., Ong, E. S., Dyk, J. A. & Evans, R. M. Nature 345, 224–229 (1990).
Yu, V. C. et al. Cell 67, 1251–1266 (1991).
Zhang, X. K., Hoffmann, B., Trans, P. B. V., Graupner, G. & Pfahl, M. Nature 355, 441–446 (1992).
Kliewer, S. A., Umesono, K., Mangelsdorf, D. J. & Evans, R. M. Nature 355, 446–449 (1992).
Leid, M. et al. Cell 68, 377–395 (1992).
Bugge, T. H., Pohl, J., Lonnoy, O. & Stunnenberg, H. G. EMBO J. 11, 1409–1418 (1992).
Marks, M. S. et al. EMBO J. 11, 1419–1435 (1992).
Levin, A. A., et al. Nature 355, 359–361 (1992).
Heyman, R. A. et al. Cell 68, 397–406 (1992).
Noda, M. et al. Proc. natn. Acad. Sci. U.S.A. 87, 9995–9999 (1990).
Umesono, K., Murakami, K. K., Thompson, C. C. & Evans, R. M. Cell 65, 1255–1266 (1991).
Morrison, N. A. et al. Science 246, 1158–1161 (1989).
Kerner, S. A., Scott, R. A. & Pike, J. W. Proc. natn. Acad. Sci. U.S.A. 86, 4455–4459 (1989).
Schüle, R. et al. Cell 61, 497–504 (1990).
Ozono, K., Liao, J., Kerner, S. A., Scott, R. A. & Pike, J. W. J. biol. Chem. 265, 21881–21888 (1990).
Bagchi, M. K., Tsai, S. Y., Tsai, M.-J. & O'Malley, B. W. Proc. natn. Acad. Sci. U.S.A. 89, 2664–2668 (1992).
Zhang, X.-K. et al. Nature 358, 587–591 (1992).
Liao, J., Ozono, K., Sone, T., McDonnell, D. P. & Pike, J. W. Proc. natn. Acad. Sci. U.S.A. 87, 9751–9755 (1990).
Sone, T., Ozono, K. & Pike, J. W. Molec. Endocr. 5, 1578–1586 (1991).
Ross, T. K., Moss, V. E., Prahl, J. M. & DeLuca, H. F. Proc. natn. Acad. Sci. U.S.A. 89, 256–260 (1992).
Luckow, B. & Schütz, G. Nucleic Acids Res. 15, 5490 (1987).
Gorman, C. M., Moffat, L. F. & Howard, B. H. Molec. cell. Biol. 2, 1044–1051 (1982).
Schreiber, E., Matthias, P., Müller, M. M. & Schaffner, W. Nucleic Acids Res. 17, 6419 (1989).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Carlberg, C., Bendik, I., Wyss, A. et al. Two nuclear signalling pathways for vitamin D. Nature 361, 657–660 (1993). https://doi.org/10.1038/361657a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/361657a0
This article is cited by
-
Effect of epigenetics on vitamin D levels: a systematic review until December 2020
Archives of Public Health (2023)
-
Evidence of a dysregulated vitamin D endocrine system in SARS-CoV-2 infected patient’s lung cells
Scientific Reports (2021)
-
VDR–SOX2 signaling promotes colorectal cancer stemness and malignancy in an acidic microenvironment
Signal Transduction and Targeted Therapy (2020)
-
Mechanisms of vitamin D on skeletal muscle function: oxidative stress, energy metabolism and anabolic state
European Journal of Applied Physiology (2019)
-
SMURF2 regulates bone homeostasis by disrupting SMAD3 interaction with vitamin D receptor in osteoblasts
Nature Communications (2017)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.