TY - JOUR

T1 - v-erbA oncogene activation entails the loss of hormone-dependent regulator activity of c-erbA.

AU - Zenke, M

AU - Muñoz, A

AU - Sap, J

AU - Vennström, B

AU - Beug, H

N1 - Keywords: Alpharetrovirus; Amino Acid Sequence; Animals; Antigens, Surface; Avian leukosis virus; Cell Transformation, Neoplastic; Cells, Cultured; Chick Embryo; Clone Cells; Erythroblasts; Erythrocytes; Gene Expression Regulation; Genetic Vectors; Hemoglobins; Molecular Sequence Data; Oncogene Proteins v-erbA; Oncogenes; Protein Conformation; Protein-Tyrosine Kinases; Receptors, Thyroid Hormone; Recombinant Fusion Proteins; Retroviridae Proteins, Oncogenic; Suppression, Genetic; Transcription, Genetic; Triiodothyronine

PY - 1990

Y1 - 1990

N2 - The v-erbA oncogene, one of the two oncogenes of the avian erythroblastosis virus, efficiently blocks erythroid differentiation and suppresses erythrocyte-specific gene transcription. Here we show that the overexpressed thyroid hormone receptor c-erbA effectively modulates erythroid differentiation and erythrocyte-specific gene expression in a T3-dependent fashion, when introduced into erythroid cells via a retrovirus. In contrast, the endogenous thyroid hormone receptor does not detectably affect erythroid differentiation. The analysis of a series of chimeric v-/c-erbA proteins suggests that the v-erbA oncoprotein has lost one type of thyroid hormone receptor function (regulating erythrocyte gene transcription in response to T3), but constitutively displays another function: it represses transcription in the absence of T3. The region responsible for the loss of hormone-dependent regulator activity of v-erbA has been mapped to the very C-terminus of c-erbA, encompassing a cluster of highly conserved amino acid residues with the potential to form an amphipathic alpha-helix.

AB - The v-erbA oncogene, one of the two oncogenes of the avian erythroblastosis virus, efficiently blocks erythroid differentiation and suppresses erythrocyte-specific gene transcription. Here we show that the overexpressed thyroid hormone receptor c-erbA effectively modulates erythroid differentiation and erythrocyte-specific gene expression in a T3-dependent fashion, when introduced into erythroid cells via a retrovirus. In contrast, the endogenous thyroid hormone receptor does not detectably affect erythroid differentiation. The analysis of a series of chimeric v-/c-erbA proteins suggests that the v-erbA oncoprotein has lost one type of thyroid hormone receptor function (regulating erythrocyte gene transcription in response to T3), but constitutively displays another function: it represses transcription in the absence of T3. The region responsible for the loss of hormone-dependent regulator activity of v-erbA has been mapped to the very C-terminus of c-erbA, encompassing a cluster of highly conserved amino acid residues with the potential to form an amphipathic alpha-helix.

M3 - Journal article

C2 - 1972036

VL - 61

SP - 1035

EP - 1049

JO - Cell

JF - Cell

SN - 0092-8674

IS - 6

ER -