Cancer is the leading cause of death in New Zealand, contributing to approximately 30% of all deaths, and the incidence of many cancers is increasing. Cancer involves abnormal, uncontrolled cell growth and cell division. Key proteins control cell division, ensuring that it does not take place too frequently. If these proteins are mutated and become non-functional, those cells can become cancerous. A thorough understanding of how these proteins function and the mechanisms cancers use to inactivate them will be crucial to development of novel treatments.
One important cell control protein is called p16 and it is one of the most frequently mutated proteins in cancer. We recently discovered that under stress conditions, p16 changes its structure and aggregates into a large fibrillar structure called amyloid. In this state it is unable to carry out its normal function. In this project we will investigate this novel amyloid fibril state of p16, by unravelling the mechanism of fibril formation, and modelling the structure of this newly-discovered state. Amyloid-forming proteins have been well studied in relation to dementias where they also play key roles, but our study will be the first to characterise amyloid proteins in cancer, promising novel insights into tumour biology.