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Inhibition of thyroid hormone action by a non-hormone binding c-erbA protein generated by alternative mRNA splicing

Nature volume 337, pages 659–661 (1989)Cite this article

Abstract

Thyroid hormone (T3) binds to a nuclear receptor protein which regulates gene expression by binding to specific DNA sequences near hormone-responsive genes1. Proteins encoded by two cellular proto-oncogenes, c-erbA α and β, bind T32,3 and can act as functional T3 receptors4,5. In rats, alternative splicing of the a-gene transcript generates at least two distinct protein products, termed r-erbAαl and r-erbAα25-7. Although these proteins bind to the same DNA sequence, r-erbAα2 does not bind T3. We show here that expression of r-erbAα2 inhibits the T3-dependent inductive effect of either r-erbAβ or r-erbAαl on expression of a T3-responsive test gene. Alternative splicing of the erbAα transcript thus generates products with opposing biological activities, suggesting a novel mechanism for the modulation of hormonal responsiveness.

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References

  1. Samuels, H. H., Forman, B. M., Horowitz, Z. D. & Ye, Z-S. J. clin. Invest. 81, 957–967 (1988).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Sap, J. et al. Nature 324, 635–640 (1986).

    Article  ADS  CAS  PubMed  Google Scholar 

  3. Weinberger, C. et al. Nature 324, 641–646 (1986).

    Article  ADS  CAS  PubMed  Google Scholar 

  4. Koenig, R. J. et al. Proc. natn. Acad. Sci. U.S.A. 85, 5031–5035 (1988).

    Article  ADS  CAS  Google Scholar 

  5. Izumo, S. & Mahdavi, V. Nature 334, 539–542 (1988).

    Article  ADS  CAS  PubMed  Google Scholar 

  6. Lazar, M. A., Hodin, R. A., Darling, D. S. & Chin, W. W. Molec. Endocrin. 2, 893–901 (1988).

    Article  CAS  Google Scholar 

  7. Mitsuhashi, T., Tennyson, G. E. & Nikodem, V. M. Proc. natn. Acad. Sci U.S.A 85, 5804–5808 (1988).

    Article  ADS  CAS  Google Scholar 

  8. Brent, G. A., Larsen, P. R., Harney, J. A., Koenig, R. J. & Moore, D. D. J. biol. Chem. 264, 178–182 (1989).

    CAS  PubMed  Google Scholar 

  9. Prost, E. & Moore, D. D. Gene 45, 107–111 (1986).

    Article  CAS  PubMed  Google Scholar 

  10. Selden, R. F., Burke-Howie, K., Rowe, M. E., Goodman, H. M. & Moore, D. D. Molec. cell. Biol. 6, 3173–3179 (1986).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Lazar, M. A. & Chin, W. W. Molec. Endocrin. 2, 479–484 (1988).

    Article  CAS  Google Scholar 

  12. Evans, R. M. Science 240, 889–895 (1988).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  13. Lee, Y-P. & Lardy, H. A. J. biol. Chem. 240, 1427–1436 (1965).

    CAS  PubMed  Google Scholar 

  14. Barker, S. B. & Klitgaard, H. M. Am. J. Physiol. 170, 81–86 (1952).

    CAS  PubMed  Google Scholar 

  15. Kolodny, J. M., Larsen, P. R. & Silva, J. E. Endocrinology 116, 2019–2028 (1985).

    Article  CAS  PubMed  Google Scholar 

  16. Lillie, J. W., Green, M. & Green, R. Cell 46, 1043–1051 (1986).

    Article  CAS  PubMed  Google Scholar 

  17. Lambert, P. F., Spaholz, B. A. & Howley, P. A. Cell 50, 69–78 (1987).

    Article  CAS  PubMed  Google Scholar 

  18. Santoro, C., Mermod, N., Andrews, P. C. & Tjian, R. Nature 334, 218–224 (1988).

    Article  ADS  CAS  PubMed  Google Scholar 

  19. Paonessa, B., Gounari, F., Frank, R. & Cortese, R. EMBO J. 7, 3115–3123 (1988).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Thompson, C. C., Weinberger, C., Lebo, R. & Evans, R. M. Science 237, 1610–1614 (1987).

    Article  ADS  CAS  PubMed  Google Scholar 

  21. Glass, C. K. et al. Nature 329, 738–741 (1987).

    Article  ADS  CAS  PubMed  Google Scholar 

  22. Koenig, R. J., Brent, G. A., Warne, R. L., Larsen, P. R. & Moore, D. D. Proc. natn. Acad. Sci. U.S.A. 84, 5670–5674 (1987).

    Article  ADS  CAS  Google Scholar 

  23. Lavin, T. N., Baxter, J. A. & Horita, S. J. biol. Chem. 263, 9418–9426 (1988).

    CAS  PubMed  Google Scholar 

  24. Benbrook, D. & Pfahl, M. Science 238, 788–791 (1987).

    Article  ADS  CAS  PubMed  Google Scholar 

  25. Nakai, A. et al. Proc. natn. Acad. Sci. U.S.A. 85, 2781–2785 (1988).

    Article  ADS  CAS  Google Scholar 

  26. Munoz, A. et al. EMBO J. 7, 155–159 (1988).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Aruffo, A. & Seed, B. Proc. natn. Acad. Sci. U.S.A. 84, 8573–8577 (1987).

    Article  ADS  CAS  Google Scholar 

  28. Larsen, P. R., Harney, J. A. & Moore, D. D. J. biol. Chem. 261, 14373–14376 (1986).

    CAS  PubMed  Google Scholar 

Download references

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Author notes

  1. Ronald J. Koenig

    Present address: Division of Endocrinology & Metabolism, University of Michigan Medical Center, 1500 East Medical Center Drive, 3920 Taubman Center, Ann Arbor, Michigan, 48109-0354, USA

  2. David D. Moore: To whom correspondence should be addressed at the Massachusetts General Hospital.

Authors and Affiliations

  1. Howard Hughes Medical Institute Laboratories, Thyroid Division, Department of Medicine, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts, 02115, USA

    Ronald J. Koenig & P. Reed Larsen

  2. Howard Hughes Medical Institute Laboratories, Genetics Division, Department of Medicine, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts, 02115, USA

    Mitchell A. Lazar, Richard A. Hodin & William W. Chin

  3. Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts, 02114, USA

    Gregory A. Brent & David D. Moore

  4. Department of Genetics, Harvard Medical School, Boston, Massachusetts, 02115, USA

    Gregory A. Brent & David D. Moore

Authors
  1. Ronald J. Koenig
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  7. David D. Moore
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Koenig, R., Lazar, M., Hodin, R. et al. Inhibition of thyroid hormone action by a non-hormone binding c-erbA protein generated by alternative mRNA splicing. Nature 337, 659–661 (1989). https://doi.org/10.1038/337659a0

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