v-erbA oncogene function in neoplasia correlates with its ability to repress retinoic acid receptor action.
The v-erbA oncoprotein of avian erythroblastosis virus is an aberrant version of a thyroid hormone receptor and functions in neoplasia by blocking erythroid differentiation and by modifying the growth properties of fibroblasts. v-erbA has been proposed to represent a novel dominant negative oncogene, acting in the cancer cell by interfering with the actions of its normal cell homologs, the thyroid hormone receptors. We report here that v-erbA can actually interfere with the actions of a variety of members of the steroid/retinoid receptor family and that the ability of v-erbA to act in neoplasia best correlates not with suppression of c-erbA action, but with interference with the retinoic acid receptor response. We suggest that v-erbA may act in neoplasia by promiscuously interfering with a retinoid-mediated differentiation process.
Department of Microbiology, University of California, Davis 95616.
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D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001717:Birds; D002352:Carrier Proteins / Q000037:antagonists & inhibitors*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D009374:Neoplasms, Experimental / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics; D018774:Oncogene Proteins v-erbA; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors; D018168:Receptors, Retinoic Acid; D015682:Retroviridae Proteins, Oncogenic / Q000502:physiology*; D013329:Structure-Activity Relationship; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D018774:Oncogene Proteins v-erbA; D011960:Receptors, Estrogen; D018168:Receptors, Retinoic Acid; D015682:Retroviridae Proteins, Oncogenic