Oncogenic mutations cause dramatic, qualitative changes in the transcriptional activity of c-Myb
- 3 October 2005
- journal article
- research article
- Published by Springer Science and Business Media LLC in Oncogene
- Vol. 25 (5), 795-805
- https://doi.org/10.1038/sj.onc.1209105
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.Keywords
This publication has 37 references indexed in Scilit:
- Positive and negative regulation of c-Myb by cyclin D1, cyclin-dependent kinases, and p27 Kip1Blood, 2005
- Both the functional specificity and autoregulative activity of two ascidian T‐box genes HrBra and HrTbx6 are likely to be mediated by the DNA‐binding domainDevelopment, Growth & Differentiation, 2005
- Stage-Specific Repression by the EKLF Transcriptional ActivatorMolecular and Cellular Biology, 2004
- Differential target gene activation by TBX2 and TBX2VP16: evidence for activation domain-dependent modulation of gene target specificityGene, 2004
- Distinct changes in gene expression induced by A-Myb, B-Myb and c-Myb proteinsOncogene, 2003
- The myb gene family in cell growth, differentiation and apoptosisOncogene, 1999
- The Myb oncoprotein: regulating a regulatorBiochimica et Biophysica Acta (BBA) - Reviews on Cancer, 1996
- Selective expression and rapid regulation of GABAA receptor subunits in geniculocortical neurons of macaque dorsal lateral geniculate nucleusVisual Neuroscience, 1996
- Vintage reds and whites: combinatorial transcription factor utilization in hematopoietic differentiationCurrent Opinion in Genetics & Development, 1994
- A functional c-myb gene is required for normal murine fetal hepatic hematopoiesisCell, 1991