The leukaemia oncogene v-erbA: a dominant negative version of ligand dependent transcription factors that regulates red cell differentiation?
The v-erbA oncogene of avian erythroblastosis virus alters the growth properties and arrests differentiation of chick erythroid progenitor cells. The v-erbA protein is a mutated, ligand independent version of the c-erbA/T3R alpha chick receptor for T3, a ligand dependent transcriptional regulator. In reconstituted systems using idealized hormone responsive elements, over-expressed v-erbA acts as a dominant repressor of transcription mediated by liganded c-erbA/T3R alpha. This property seems to account for at least part of the phenotype of AEV transformed erythroid cells and for the transcriptional repression of some erythrocyte specific genes. However, v-erbA is likely to interfere with regulatory circuits other than those directly regulated by T3 receptors. Aspects of this hypothesis are discussed in the context of available evidence for the role of T3 and other hormones in erythroid progenitor cells proliferation/differentiation.
Institut-Curie, Section de Biologie, Orsay, France.
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Ghysdael
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H
Beug
D000818:Animals; D001717:Birds; D002454:Cell Differentiation / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D004912:Erythrocytes / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D018774:Oncogene Proteins v-erbA; D011988:Receptors, Thyroid Hormone / Q000235:genetics; D015682:Retroviridae Proteins, Oncogenic / Q000502:physiology*
D018774:Oncogene Proteins v-erbA; D011988:Receptors, Thyroid Hormone; D015682:Retroviridae Proteins, Oncogenic