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9-Cis retinoic acid stereoisomer binds and activates the nuclear receptor RXRα

Abstract

VITAMIN A (retinol) and its natural derivatives are required for many physiological processes1–3. The activity of retinoids is thought to be mediated by interactions with two subfamilies of nuclear retinoic acid receptors, RAR and RXR. The RARs bind all-trans retinoic acid (t-RA) with high affinity and alter gene expression as a consequence of this direct ligand interaction4–10. RXRα is activated by t-RA, yet has little binding affinity for this ligand (ref. 11) t-RA may be converted to a more proximate ligand that directly binds and activates RXRα, and we have developed a method of nuclear receptor-dependent ligand trapping to test this hypothesis. Here we report the identification of a stereoisomer of retinoic acid, 9-cis retinoic acid, which directly binds and activates RXRα. These results suggest a new role for isomerization in the physiology of natural retinoids.

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References

  1. Thaller, C. & Eichele, G. Nature 327, 625–628 (1987).

    Article  ADS  CAS  Google Scholar 

  2. Roberts, A. B. & Sporn, M. B., The Retinoids Vol 2 (eds Sporn, M. B., Roberts, A. B, & Goodman, DeW. S.) 209–286 (Academic, Orlando, 1984).

    Book  Google Scholar 

  3. Coward, W. A., Howell, J. M., Thompson, J. N. & Pitt, G. A. J. Br. J. Nutr. 23, 619–626 (1969).

    Article  CAS  Google Scholar 

  4. Glguere, V., Ong, E. S., Segui, P. & Evans, R. M. Nature 330, 624–629 (1987).

    Article  ADS  Google Scholar 

  5. Petkovich, M., Brand, N. J., Krust, A. & Chambon, P. Nature 330, 444–450 (1987).

    Article  ADS  CAS  Google Scholar 

  6. Åström, A., Pettersson, U., Krust, A., Chambon, P. & Vorhees, J. J. Biochem. biophys. Res. Comm. 173, 339–345 (1990).

    Article  Google Scholar 

  7. Yang, N., Schüle, R., Mangelsdorf, D. J. & Evans, R. M. Proc. natn. Acad. Sci. U.S.A. 88, 3559–3563 (1991).

    Article  ADS  CAS  Google Scholar 

  8. Graupner, G. et al. Biochem. biophys. Res. Comm. 179, 1554–1561 (1991).

    Article  CAS  Google Scholar 

  9. Brand, N. et al. Nature 332, 850–853 (1988).

    Article  ADS  CAS  Google Scholar 

  10. Krust, A., Kastner, Ph., Petkovich, M., Zelent, A. & Chambon, P. Proc. natn. Acad. Sci. U.S.A. 86, 5310–5314 (1989).

    Article  ADS  CAS  Google Scholar 

  11. Mangelsdorf, D. J., Ong, E. S., Dyck, J. A. & Evans, R. M. Nature 345, 224–229 (1990).

    Article  ADS  CAS  Google Scholar 

  12. Nervi, C. J., Grippo, J. F., Sherman, M. I., George, M. D. & Jetten, A. M. Proc. natn. Acad. Sci. U.S.A. 86, 5854–5858 (1989).

    Article  ADS  CAS  Google Scholar 

  13. Cavey, M. T., Martin, B., Carlavan, I. & Shroot, B. Analyt. Biochem. 186, 19–23 (1990).

    Article  CAS  Google Scholar 

  14. Crettaz, M., Baron, A., Siegenthaler, G. & Hunziker, W. Biochem. J. 272, 391–397 (1990).

    Article  CAS  Google Scholar 

  15. Delescluse, C. et al. Molec. Pharmac. 40, 556–562 (1991).

    CAS  Google Scholar 

  16. McClean, S. W., Ruddel, M. E., Gross, E. G., DeGiovanna, J. J. & Peck, G. L. Clin. Chem. 28, 693–696 (1982).

    CAS  PubMed  Google Scholar 

  17. De Leenheer, A. P. & Lambert, W. E. Meth. Enzym. 189, 104–111 (1990).

    Article  CAS  Google Scholar 

  18. Huselton, C. A. et al. in Liquid Chromatographyl Mass Spectrometry Applications in Agricultural. Pharmaceutical and Environmental Chemistry (ed. Brown, M. A.) 166–178 (American Chemical Society, Washington DC, 1990).

    Book  Google Scholar 

  19. Napoli, J. L. Meth. Enzym. 123, 112–124 (1986).

    Article  CAS  Google Scholar 

  20. Mangelsdorf, D. J. et al. Cell 66, 555–561 (1991).

    Article  CAS  Google Scholar 

  21. Glass, C. K., Lipkin, S. M., Devary, O. V. & Rosenfeld, M. G. Cell 59, 697–708 (1989).

    Article  CAS  Google Scholar 

  22. Husmann, M. et al. Molec. cell. Biol. 11, 4097–4103 (1991).

    Article  CAS  Google Scholar 

  23. Hudson, L. G., Santon, J. B., Glass, C. K. & Gill, G. N. Cell 62, 1165–1175 (1990).

    Article  CAS  Google Scholar 

  24. Zhang, X. K. et al. New Biol. 2, 169–181 (1991).

    Google Scholar 

  25. Graupner, G., Wills, K. N., Tzukerman, M., Zhang, X.-K. & Pfahl, M. Nature 340, 653–656 (1989).

    Article  ADS  CAS  Google Scholar 

  26. Shüle, R. et al. Proc. natn. Acad. Sci. U.S.A. 88, 6092–6096 (1991).

    Article  ADS  Google Scholar 

  27. Glass, C. K., Devary, O. V. & Rosenfeld, M. G. Cell 63, 729–738 (1990).

    Article  CAS  Google Scholar 

  28. Yu, V. C. et al. Cell 67, 1251–1266 (1991).

    Article  CAS  Google Scholar 

  29. Green, S., Isseman, I. & Scheer, E. Nucleic Acids Res. 16, 369 (1988).

    Article  CAS  Google Scholar 

  30. Dalman, F. C. et al. Biochemistry 30, 5605–5608 (1991).

    Article  CAS  Google Scholar 

  31. Garland, W. A. et al. Trends analyt. Chem. 3, 177–184 (1991).

    Article  Google Scholar 

  32. Scatchard, G. Ann, N. Y. Acad. Sci. 51, 660–672 (1949).

    Article  ADS  CAS  Google Scholar 

  33. Grippo, J. F. & Gudas, L. J. J. biol. Chem. 262, 4492–4500 (1987).

    CAS  PubMed  Google Scholar 

  34. Chen, C. & Okayama, H. Molec. cell. Biol. 7, 2745–2752 (1987).

    Article  CAS  Google Scholar 

  35. Rosenthal, N. Meth. Enzym. 152, 704–720 (1987).

    Article  CAS  Google Scholar 

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Levin, A., Sturzenbecker, L., Kazmer, S. et al. 9-Cis retinoic acid stereoisomer binds and activates the nuclear receptor RXRα. Nature 355, 359–361 (1992). https://doi.org/10.1038/355359a0

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