Arginine methylation – a new player in cancer pathogenesis
Protein modifications expand the functional diversity of the proteome enabling dynamic modulation of cellular processes, but are often deregulated during cancer pathogenesis. Arginine methylation, catalysed by protein arginine methyltransferases (PRMTs), was identified over 45 years ago, however the significance of this modification for oncogenesis and malignant progression is only just becoming apparent. In particular, expression of many PRMTs correlates with a poorer cancer prognosis and has thus attracted significant attention as a novel drug target. Despite this potential, the mechanisms by which PRMTs contribute to cancer progression is largely unknown. The Davies lab aims to increase our understanding into the biology of PRMTs and arginine methylation. Using breast cancer as a model, the questions we are currently addressing are:
- How is PRMT5 regulating the DNA damage response?
- What is the mechanism by which PRMT5 controls the function of breast cancer stem cells?
- Do PRMTs initiate and/or facilitate cancer progression and can a cancer arginine methylome be identified?
To address all of these questions, the Davies lab takes a multidisciplinary approach that includes molecular and cell biology, flow cytometry, quantitative proteomics, protein biochemistry (methylation assays, immunoprecipitations), genomic analysis (RNA-Seq and ChIP-Seq), single cell analysis, analysis of patient sample by IHC and functional assays, microscopy and animal models of cancer (genetically engineered, cell line xenografts and patient-derived xenografts (PDXs)).
Dr Davies is the supervisor on the below project: