INDIVIDUAL REPEATS OF DROSOPHILA MYB CAN FUNCTION IN TRANSFORMATION BY V-MYB

The v-Myb protein binds to specific DNA sequences and can regulate gen e expression. The DNA-binding domain of v-Myb contains the second and third of the three highly conserved tandem repeats found in c-MYb. In general, the ability of mutant forms of v-Myb to transform correlates with their ability to trans activate transcription. Two mutations with in the DNA-binding domain of v-Myb which preserve DNA binding in vitro but fail to trans activate or transform have been described. These re sults suggested that this highly conserved domain might function in sp ecific protein-protein interactions, as well as in DNA binding. We the refore tested the ability of a related protein domain from Drosophila melanogaster to substitute functionally for the homologous region of v -Myb. We found that either the second or third repeat of Drosophila My b, but not both, could function in trans-activation and transformation by v-Myb. The hybrid containing both the second and third repeats of Drosophila Myb bound to DNA but failed to trans activate transcription either in the context of v-Myb or as a v-Myb-VP16 fusion protein. The se results demonstrate that although the protein-DNA contacts made by the Myb repeats have been conserved during the evolution of animals, t he protein-protein interactions have diverged.