v-erbA oncogene activation entails the loss of hormone-dependent regulator activity of c-erbA.
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.
Zenke
M
M
Institute of Molecular Pathology, Vienna, Austria.
Muñoz
A
A
Sap
J
J
Vennström
B
B
Beug
H
H
D001355:Alpharetrovirus / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D000954:Antigens, Surface / Q000032:analysis; D001354:Avian Leukosis Virus / Q000235:genetics*; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D002642:Chick Embryo; D002999:Clone Cells; D004900:Erythroblasts / Q000201:enzymology; D004912:Erythrocytes / Q000201:enzymology; D005786:Gene Expression Regulation / Q000187:drug effects; D005822:Genetic Vectors; D006454:Hemoglobins / Q000096:biosynthesis; D008969:Molecular Sequence Data; D018774:Oncogene Proteins v-erbA; D009857:Oncogenes; D011487:Protein Conformation; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D011988:Receptors, Thyroid Hormone / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D015682:Retroviridae Proteins, Oncogenic / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D013489:Suppression, Genetic; D014158:Transcription, Genetic / Q000187:drug effects*; D014284:Triiodothyronine / Q000494:pharmacology*
D000954:Antigens, Surface; D006454:Hemoglobins; D018774:Oncogene Proteins v-erbA; D011988:Receptors, Thyroid Hormone; D011993:Recombinant Fusion Proteins; D015682:Retroviridae Proteins, Oncogenic; D014284:Triiodothyronine; D011505:Protein-Tyrosine Kinases