The role of glutathionylation in tumorigenesis

Reactive oxygen species (ROS) are produced as part of normal cellular processes, and are crucial to many functions of the cell. However in excess, ROS may damage the cell and lead to cancer. It is therefore important that levels of ROS are tightly controlled and the cell has developed a number of regulatory mechanisms to ensure this. One such mechanism involves glutathione, a small thiol compound which acts to buffer ROS in the cell. Recently, there has been growing interest in the protection of proteins from the deleterious effects of ROS by the addition of glutathione - a process known as glutathionylation, which has been linked to a number of human diseases including cancer, and which has been reputed to involve the enzyme glutathione transferase Pi (GSTP). We have studied GSTP for many years, demonstrating a role for this enzyme in both tumorigenesis and drug resistance, although no clear mechanism has been identified. We now wish to study the relationship between glutathionylation, GSTP and cancer, and will use a number of novel cell and animal models to do so, with the hope of identifying potential new drug targets on which cancer treatments may be based.