v-erbA acts on retinoic acid receptors in immature avian erythroid cells.
The v-erbA oncogene of avian erythroblastosis virus (AEV) encodes an aberrant version of a gene for a thyroid hormone receptor (c-erbA) and functions in neoplasia by blocking erythroid differentiation and altering the growth properties of fibroblasts. The v-erbA gene has been proposed to act as a dominant negative allele, functioning by interfering with the actions of its normal cell homologs, the thyroid hormone receptors. The v-erbA protein can also, however, interfere with the actions of other members of the nuclear hormone receptor family, and it has been proposed that interference with a retinoic acid-mediated response may be a crucial determinant of v-erbA's function in the cancer cell. Here we report that the ability of v-erbA to interfere with retinoic acid receptor (RAR) action extends to the neoplastic erythroid cell and that v-erbA can inhibit transcriptional activation by all three isoforms (alpha, beta, and gamma) of RAR. Overexpression of RAR-alpha was found to partially overcome the presumptive v-erbA block to transcription in the erythroleukemic cell. These results are consistent with our hypothesis that v-erbA can act in neoplasia by interfering with a retinoic acid-mediated signal transduction pathway.
Sande
S
S
Department of Microbiology, University of California, Davis 95616.
Sharif
M
M
Chen
H
H
Privalsky
M
M
D001355:Alpharetrovirus / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000096:biosynthesis / Q000187:drug effects*; D002461:Cell Line, Transformed; D002645:Chickens; D015672:Erythroid Precursor Cells / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic; D005814:Genes, Viral / Q000235:genetics*; D014644:Genetic Variation; D008969:Molecular Sequence Data; D018774:Oncogene Proteins v-erbA; D012333:RNA, Messenger / Q000096:biosynthesis; D018168:Receptors, Retinoic Acid; D015682:Retroviridae Proteins, Oncogenic / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects
D002352:Carrier Proteins; D018774:Oncogene Proteins v-erbA; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D015682:Retroviridae Proteins, Oncogenic