We have been studying a pair of proteins that have an unusual function as gate-keepers in tissues by providing a throttle to signals that normally promote growth and adoption of particular cell fates. The growth inhibitory effects of these proteins is cleverly bipassed in a large number of human cancers. We have created strains of mice and engineered cells in which we can turn off these proteins in specific tissues and cell types (such as liver, brain and immune cells). When switched off in the liver and immune cells, all of the animals succumb to liver overgrowth and lymphoma, respectively. This proposal aims to understand the roles of these proteins in cancer, how inhibition of these proteins promotes tumorigenesis and whether turning them back on again can block tumour growth, once it has occurred.