DNA Binding Properties of the Thyroid Hormone Receptor/c-erbA Protein and Its Viral Homologue P75gag-v-erbA

The erbA proteins encoded by the cellular proto-oncogene c-erbA and its viral homologue v-erbA differ in their DNA binding region as well as in other domains. We have investigated the possible differences in regulation of transcription and the binding to thyroid hormone responsive elements (TREs) by these proteins. The results show that in chicken erythroblasts P75gag-v-erbA constitutively represses expression of the genes for band 3 and carbonic anhydrase, whereas the normal thyroid hormone receptor represses expression in the absence of ligand and induces transcription upon binding of hormone. In a direct test of binding to TREs in the rat growth hormone gene the c-erbA protein bound with high affinity, whereas the viral ptotein exhibited no binding at all. The experiments demonstrate that the two proteins can recognize the same regulatory elements in erythroblasts but with distinct effects on transcription, and that other TREs bind to only one of the proteins, suggesting that mutations in the primary structure of the viral protein has altered its specificity.