Dissection of O-glycosylation of nuclear and cytoplasmic proteins

The recent decoding of the human genome surprisingly revealed that humans possess a relatively small number of genes. Yet despite this apparently small number, we are rather complex beings. Genes are a special code that can be read out to form proteins, which are responsible for the vast majority of biochemical process within our bodies. This apparent inconsistency between the number of genes and the complexity of humans can be, in part, accounted for by various 'post-translational modifications' of human proteins. These types of modification are often additional molecule groups that are added onto certain positions in the protein and can change its activity. Dr. Tracey Gloster is interested in a modification where there is addition and removal of a sugar called 'N-acetylglucosamine’. Disruptions to this modification are implicated in conditions such as diabetes, cancer and neurodegenerative diseases. The enzyme responsible for adding the N-acetylglucosamine modifies a large number of completely different target proteins. Little is known about how the enzyme recognizes its targets and modifies them at the correct position to ensure they carry out their proper function. Gloster is investigating a specific domain on this enzyme that could hold the answer. There are multiple sites on this interacting domain which she believes each recognize different sets of target proteins. By finding proteins that are modified by this protein and determining the exact region of the target protein that binds to the enzyme, it may be possible to block the enzyme’s action. This could open up new therapeutic approaches in the treatment of diabetes and other diseases.