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

Jan Sap, Alberto Muñoz, Jackie Schmitt, Henk Stunnenberg, Björn Vennström

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359 Citaten (Scopus)

Samenvatting

SEVERAL recent observations such as the identification of the cellular homologue of the v-erb-A oncogene as a thyroid-hormone receptor 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 erythroblasts. Mutations in v-erb-A protein have led to the loss of its affinity for thyroid hormones but do not affect its DNA-binding ability a property required for biological activity. 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.

Originele taal-2Engels
Pagina's (van-tot)242-244
Aantal pagina's3
TijdschriftNature
Volume340
Nummer van het tijdschrift6230
DOI's
StatusGepubliceerd - 1989
Extern gepubliceerdJa

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