The Ras oncogene mediates a variety of biological effects which promote tumorigenic transformation. However, activated forms of Ras also have a surprising number anti-transformation aspects. They can induce senesence, cell cycle arrest and even death by apoptosis. The mechanisms behind these anti-neolastic effects remain poorly understood. We have identified a family of novel Ras effectors which appear to mediate some of the anti-neoplastic activities of Ras. especialy apoptosis. We have now determined that at least three members of this family exhibit all the classic hall marks of Ras effectors yet also demonstrate the properties of tumor suppressors. Namely, the mediate inhibition of cell growth and transformation and are frequently down-regulated by epigenetic mechanisms during tumor development. We now have preliminary data that two other members of this family have similar properties. Thus, we have identified and partially characterized a novel class of Ras activated tumor suppressor.
