BACK-MUTATION OF THE V-ETS TO THE C-ETS CARBOXY-TERMINAL AMINO-ACIDS IN THE P135(GAG-MYB-ETS) RESULTS IN CHICKEN NEURORETINA CELLS TRANSFORMATION AND LOSS OF BASIC FIBROBLAST GROWTH-FACTOR RESPONSIVENESS

The v-Myb, v-Ets containing E26 retrovirus (called in this work E26ABC ) induces the proliferation of chicken neuroretina (CNR) cells in mini mal medium, strongly stimulated by basic Fibroblast Growth Factor (bFG F) which confers on them the ability to form colonies in soft agar. V- Ets differs from its cellular counterpart c-Ets-l by two point mutatio ns and by the replacement of the 13 last C-terminal amino acids by 16 unrelated residues as a consequence of DNA segment inversion in the vi ral sequence. It has been documented that this different C-terminal se quence influences DNA binding activity and specificity. Replacement in E26ABC virus of the sequence encoding the 16 v-Ets last C-terminal am ino acids by the sequence encoding the 13 c-Ets-l derived C-terminus ( virus E26ABO), results in the production of a P135(gag-myb-ets) with m odified biological properties on CNR cells. E26ABO infected CNR cells proliferate in minimal medium more efficiently than E26ABC, are unresp onsive to bFGF and able to grow in soft agar. In contrast, CNR cells i nfected by viruses encoding Myb and Ets proteins either in the E26ABO or in the E26ABC configuration are bFGF responsive. Since Myb alone is sufficient to induce bFGF responsiveness on CNR cells, these results suggest that the c-Ets-l C-terminus interferes with the Myb activity o f the E26ABO P135(gag-myb-ets) protein in CNR cells.