v-erbA stimulates quail myoblast differentiation in a T3 independent, cell-specific manner.

The v-erbA oncoprotein represents a mutated version of a thyroid hormone receptor, responsible for the induction of a differentiation arrest in chicken erythroid cells. We have studied the influence of v-erbA on proliferation and differentiation of avian myoblasts. Secondary quail myoblast cultures were infected either with an avian retrovirus carrying the v-erbA oncogene in association with the neomycin resistance gene, or with a control deleted v-erbA/neoR alpha retrovirus. We report here that v-erbA expression led to an increase in myoblast proliferation and to a surprising stimulation of quail myoblast terminal differentiation. In addition, these effects occurred in the presence or absence of T3, and v-erbA did not suppress T3 influence on myoblasts. Transient transfection assays demonstrated that, in contrast to its action in HeLa cells, v-erbA was unable to repress the transcriptional activation of a TRE-CAT reporter gene by liganded c-erbA alpha receptors in quail myoblasts. We also observed that the AP-1/c-erbA/v-erbA interactions are not functional in quail myoblasts. These data suggest that, in these cells, v-erbA action does not interfere with T3 induced mechanisms. They also demonstrate a cell specificity for the v-erbA pathway. Lastly, expression of c-erbA/v-erbA chimeric proteins and of the S61G v-erbA mutant indicates that the DNA binding domain of v-erbA, and more specifically serine 61, is directly involved in the enhancement of myoblast differentiation by the oncoprotein.