Repression of transcription mediated at a thyroid hormone response element by the v-erb-A oncogene product.
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-alpha 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.
Sap
J
J
European Molecular Biology Laboratory, Heidelberg, FRG.
Muñoz
A
A
Schmitt
J
J
Stunnenberg
H
H
Vennström
B
B
D001483:Base Sequence; D005786:Gene Expression Regulation / Q000187:drug effects*; D007163:Immunosorbent Techniques; D008979:Moloney murine leukemia virus / Q000235:genetics; D018774:Oncogene Proteins v-erbA; D009857:Oncogenes; D010957:Plasmids; D011401:Promoter Regions, Genetic; D011988:Receptors, Thyroid Hormone / Q000502:physiology; D012091:Repetitive Sequences, Nucleic Acid; D012191:Retroviridae Proteins / Q000235:genetics* / Q000494:pharmacology; D012689:Sequence Homology, Nucleic Acid; D018139:Simplexvirus / Q000235:genetics; D013963:Thyroid Hormones / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects*; D014162:Transfection; D014284:Triiodothyronine / Q000494:pharmacology
D018774:Oncogene Proteins v-erbA; D011988:Receptors, Thyroid Hormone; D012191:Retroviridae Proteins; D013963:Thyroid Hormones; D014284:Triiodothyronine