The v-erbA oncogene (review)

The v-erbA oncogene product is a nuclear protein and belongs to the superfa mily of nuclear hormone receptors. The v-ErbA oncoprotein is involved in ne oplastic transformation leading to acute erythroleukemia and sarcomas. The cellular homolog of v-ErbA oncoprotein is the thyroid hormone receptor alph a (c-erbA alpha or TR alpha). While TR has the dual role to silence gene ex pression in the absence of hormone and activate genes in the presence of th e ligand, triiodothyronine, the v-ErbA oncoprotein has lost the ability to activate genes. The oncoprotein is thought to repress, in a constitutive ma nner, a certain set of genes which prevent cellular transformation. The mec hanism of gene silencing is partly understood and involves the so-called co repressors. Several types of corepressors have been identified so far. Simi larly, gene silencing by corepressors also plays a role in myeloid transfor mation by the retinoic acid receptor (RAR) which is involved in translocati ons, such as PML-RAR. The v-erbA oncogene was isolated from a retrovirus wh ich contains, in addition to v-erbA, the oncogene v-erbB. The viral erbB ge ne encodes an EGF-receptor derivative, which is a constitutively active tyr osine kinase. Cellular transformation is enhanced when both oncoproteins ar e expressed. However, the mechanisms of cellular transformation by v-ErbA a lone or in synergy with v-ErbB remain unclear. Novel insights into the mech anism of cellular transformation by v-ErbA, the role of corepressors and th e role of the cross talk between the EGF-receptor and v-ErbA will be discus sed.