Abstract
Protein hydroxylation is the site-specific enzymatic incorporation of a single oxygen atom into an amino acid side chain. It is mostly widely known for functions in collagen synthesis and oxygen sensing and, through its role in demethylation, epigenetics and gene expression control. A less well-known sub-family of protein hydroxylases are characterised by the presence of a Jumonji-C (JmjC) catalytic domain and emerging roles in tumour cell biology. These enzymes are attracting interest as targets of hypoxia and oncometabolites and for their potential for developing novel therapeutics.
In my talk I will first introduce the hydroxylase enzyme family, and then summarise two largely unpublished stories that aim to highlight the potential diversity of hydroxylase biology. I will explain how we think a histidine hydroxylase couples nucleolar ribosome biogenesis to plasma membrane biology, and then describe the role of an arginine hydroxylase in DNA replication fidelity and genome stability.
Biography
Prof. Mathew Coleman undertook his PhD at the ICR with the Olson and Marshall groups studying the role of small GTPases in apoptosis and the cell cycle. In 2002 he moved to the Abramson Family Cancer Research Centre in Philadelphia to study oncogenic B-Raf signalling. In 2004 he returned to the UK and switched fields to work with Peter Ratcliffe on protein hydroxylation.
With an independent fellowship he established a team to work on the role of ribosomal hydroxylases in 2009.
In 2013 he moved his group to the University of Birmingham funded by an MRC NIRG to focus on protein hydroxylases that target the protein synthesis machinery. In 2017 his team was awarded a CRUK Programme Foundation Award to investigate the role of histidine, arginine, and lysine hydroxylases in cancer.