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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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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DOI: https://doi.org/10.1038/340242a0
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