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

The v-Myb protein binds to specific DNA sequences and can regulate gene 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 within the DNA-binding domain of v-Myb which preserve DNA binding in vitro but fail to trans activate or transform have been described. These results suggested that this highly conserved domain might function in specific protein-protein interactions, as well as in DNA binding. We therefore 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 Myb, 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. These results demonstrate that although the protein-DNA contacts made by the Myb repeats have been conserved during the evolution of animals, the protein-protein interactions have diverged.