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

TY - JOUR

T1 - Repression of transcription mediated at a thyroid hormone response element by the v-erb-A oncogene product.

AU - Sap, J

AU - Muñoz, A

AU - Schmitt, J

AU - Stunnenberg, H

AU - Vennström, B

N1 - Keywords: Base Sequence; Gene Expression Regulation; Immunosorbent Techniques; Moloney murine leukemia virus; Oncogene Proteins v-erbA; Oncogenes; Plasmids; Promoter Regions (Genetics); Receptors, Thyroid Hormone; Repetitive Sequences, Nucleic Acid; Retroviridae Proteins; Sequence Homology, Nucleic Acid; Simplexvirus; Thyroid Hormones; Transcription, Genetic; Transfection; Triiodothyronine

PY - 1989

Y1 - 1989

N2 - 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.

AB - 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.

U2 - 10.1038/340242a0

DO - 10.1038/340242a0

M3 - Journal article

C2 - 2569164

SN - 0028-0836

VL - 340

SP - 242

EP - 244

JO - Nature

JF - Nature

IS - 6230

ER -