Victoria Cowling’s group
investigates how c-Myc oncogene functions
biochemically and the signalling pathways it regulates
to drive cell proliferation and tumour formation.
Currently the group is investigating the mechanism and
biological significance of c-Myc induced mRNA cap
methylation, an essential step in mRNA
translation.c-Myc is essential for almost all mammalian cells to grow and proliferate. It is upregulated by growth factors and probably drives cell proliferation by co-ordinately regulating the expression of a number of genes and signalling pathways. Myc can also function as an oncogene; when Myc expression is deregulated it promotes unrestrained cell growth and proliferation. In addition, elevated Myc expression promotes apoptosis and growth arrest, both of which have the potential to restrict Myc oncogenic function. Our research focus is to investigate how Myc drives these diverse biological responses. We study both how Myc functions biochemically, and the signalling pathways it activates.
Myc proteins function biochemically as a weak but pleiotropic transcription factors. We recently found that Myc also regulates gene expression by a novel mechanism, that is by promoting methylation of the 5’mRNA cap, an essential step for mRNA translation. This revealled that although Myc is a weak transcription factor it is rather efficient at upregulating expression of specific proteins via the combined the effects of increased transcription and increased mRNA cap methylation and translation. We are currently investigating which proteins are best upregulated by this dual mechanism and the role of these proteins in mediating the biological effects of Myc. We also made the unexpected finding that, for a subset of genes, Myc can upregulate mRNA cap methylation and protein expression independently of transcription. We are investigating the identity and function of this novel set of Myc targets. In addition, we are studying the mechanism of Myc-induced mRNA cap methylation and how other signalling pathways and transcription factors influence this essential step in gene regulation.
