The transcription factor c-Myb is essential during the development of stem cells in the hematopoietic system, as well as in colonic crypts and neurogenic regions. By controlling the expression of specific target genes and gene programs, c-Myb contributes to the development of these cells. Deregulation of c-Myb, or mutations in the MYB gene, can lead to cancer. Understanding how c-Myb's activity is regulated by post-translational modifications and interaction with other proteins, and how this activity translates to epigenetic changes and activation of target genes, is therefore important.
As a proto-oncogene the transcription factor c-Myb can undergo oncogenic activation. We believe that it is important to unravel the molecular mechanisms of c-Myb action, given its key role in hematopoiesis and leukaemogenesis. Our ongoing research is directed towards four main objectives:
- Defining molecular functions of novel coactivators of c-Myb.
- Unravelling mechanisms of PTM-mediated control of c-Myb activity, focusing on SUMOylation and phosphorylation.
- Investigate how c-Myb through PTMs and cofactor recruitment establishes epigenetic signature(s).
- Identifying novel and robust target genes of c-Myb.
The question of how these mechanism is affected by, or contribute to, oncogenic activation runs as a thread through the four objectives.