Abstract
The v-Myb oncoprotein encoded by Avian Myeloblastosis Virus is highly oncogenic, induces leukemias in chickens and mice and transforms immature hematopoietic cells in vitro. The v-Myb protein is a mutated and truncated version of c-Myb, a DNA-binding transcription factor expressed in many cell types that is essential for normal hematopoiesis. Previous studies suggested that two types of differences, DNA binding domain mutations and the deletion of a C-terminal negative regulatory domain were important for increasing the transforming activity of v-Myb. Here, we combined structure-function studies of the v-Myb and c-Myb proteins with unbiased microarray-based transcription assays to compare the transcriptional specificities of the two proteins. In human cells, the v-Myb and c-Myb proteins displayed strikingly different activities and regulated overlapping, but largely distinct sets of target genes. Each type of mutation that distinguished v-Myb from c-Myb, including the N- and C-terminal deletions, DNA binding domain changes and mutations in the transcriptional activation domain, affected different sets of target genes and contributed to the different activities of c-Myb and v-Myb. The results suggest that v-Myb is not just a de-repressed version of c-Myb. Instead, it is a distinct transcriptional regulator with a unique set of activities.
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Acknowledgements
This research was supported by grants to SAN from the USPHS/National Cancer Institute (R01CA58443) and by institutional support from the University of New Mexico Health Sciences Center and the UNM Cancer Research and Treatment Center. Some experiments used the facilities or services provided by the Keck-UNM Genomics Resource, a facility supported by a grant from the WM Keck Foundation as well as the State of New Mexico and the UNM Cancer Research and Treatment Center.
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Liu, F., Lei, W., O'Rourke, J. et al. Oncogenic mutations cause dramatic, qualitative changes in the transcriptional activity of c-Myb. Oncogene 25, 795–805 (2006). https://doi.org/10.1038/sj.onc.1209105
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DOI: https://doi.org/10.1038/sj.onc.1209105
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