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.
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Department of Microbiology, State University of New York, Stony Brook 11794-5222.
Lipsick
J S
JS
D000123:Acetyltransferases; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002478:Cells, Cultured; D002642:Chick Embryo; D004268:DNA-Binding Proteins / Q000378:metabolism; D004330:Drosophila / Q000235:genetics*; D005822:Genetic Vectors; D006412:Hematopoietic Stem Cells; D016177:Macrophage-1 Antigen / Q000096:biosynthesis; D008969:Molecular Sequence Data; D020626:Oncogene Proteins v-myb; D011506:Proteins / Q000235:genetics; D011784:Quail; D011993:Recombinant Fusion Proteins / Q000235:genetics; D012091:Repetitive Sequences, Nucleic Acid; D012190:Retroviridae / Q000235:genetics; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; D016177:Macrophage-1 Antigen; D020626:Oncogene Proteins v-myb; D011506:Proteins; D011993:Recombinant Fusion Proteins; D015682:Retroviridae Proteins, Oncogenic; D000123:Acetyltransferases; C077509:mim-1 protein, Gallus gallus