The v-erbA oncogene (review).
The v-erbA oncogene product is a nuclear protein and belongs to the superfamily of nuclear hormone receptors. The v-ErbA oncoprotein is involved in neoplastic transformation leading to acute erythroleukemia and sarcomas. The cellular homolog of v-ErbA oncoprotein is the thyroid hormone receptor alpha (c-erbA alpha or TRalpha). While TR has the dual role to silence gene expression in the absence of hormone and activate genes in the presence of the ligand, triiodothyronine, the v-ErbA oncoprotein has lost the ability to activate genes. The oncoprotein is thought to repress, in a constitutive manner, a certain set of genes which prevent cellular transformation. The mechanism of gene silencing is partly understood and involves the so-called corepressors. Several types of corepressors have been identified so far. Similarly, gene silencing by corepressors also plays a role in myeloid transformation by the retinoic acid receptor (RAR) which is involved in translocations, such as PML-RAR. The v-erbA oncogene was isolated from a retrovirus which contains, in addition to v-erbA, the oncogene v-erbB. The viral erbB gene encodes an EGF-receptor derivative, which is a constitutively active tyrosine kinase. Cellular transformation is enhanced when both oncoproteins are expressed. However, the mechanisms of cellular transformation by v-ErbA alone or in synergy with v-ErbB remain unclear. Novel insights into the mechanism of cellular transformation by v-ErbA, the role of corepressors and the role of the cross talk between the EGF-receptor and v-ErbA will be discussed.
Thormeyer
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Genetic Institute, Justus-Liebig-University, D-35392 Giessen, Germany.
Baniahmad
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D002471:Cell Transformation, Neoplastic; D002472:Cell Transformation, Viral; D066246:ErbB Receptors; D018776:Genes, erbA; D006801:Humans; D018774:Oncogene Proteins v-erbA; D012190:Retroviridae
D018774:Oncogene Proteins v-erbA; D066246:ErbB Receptors