Repression of transcription mediated at a thyroid hormone response element by the v-erb-A oncogene product (original) (raw)

Nature volume 340, pages 242–244 (1989)Cite this article

Abstract

SEVERAL recent observations1,2, such as the identification of the cellular homologue of the v-erb-A oncogene as a thyroid-hormone receptor3,4, have strongly implicated nuclear oncogenes in transcriptional control mechanisms. The v-erb-A oncogene blocks the differentiation of erythroid cells, and changes the growth requirements of fibroblasts and erythroblasts5–7. Mutations in v-erb-A protein have led to the loss of its affinity for thyroid hormones3,8 but do not affect its DNA-binding ability8,9, a property required for biological activity9. We report here the identification of a novel thyroid-hormone response element (TRE) in the long terminal repeat of Moloney murine leukaemia virus that binds the c-erb-A-α protein. The v-erb-A protein abolishes the responsiveness of this TRE to thyroid hormone, although it has a lower affinity than the normal receptor for the TRE. The data indicate that overexpressed v-erb-A protein negatively interferes with normal transcriptional-control mechanisms, and that amino-acid substitutions have altered its DNA-binding properties.

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Author notes

  1. Jan Sap
    Present address: Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel, 76100
  2. Björn Vennström: To whom correspondence should be addressed.

Authors and Affiliations

  1. European Molecular Biology Laboratory, Postfach 102209, Meyerhofstrasse 1, D-6900, Heidelberg, FRG
    Jan Sap, Alberto Muñoz, Jackie Schmitt & Henk Stunnenberg
  2. Institute de Investigaciones Biomedicas, Universidad Autonoma, Facultad de Medicina, Arzobispo Morcillo 4, 28029, Madrid, Spain
    Alberto Muñoz
  3. Department of Molecular Biology, Karolinska Institutet, Box 60400, S-104 01, Stockholm, Sweden
    Björn Vennström

Authors

  1. Jan Sap
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  2. Alberto Muñoz
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  3. Jackie Schmitt
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  4. Henk Stunnenberg
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  5. Björn Vennström
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Sap, J., Muñoz, A., Schmitt, J. et al. Repression of transcription mediated at a thyroid hormone response element by the v-erb-A oncogene product.Nature 340, 242–244 (1989). https://doi.org/10.1038/340242a0

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