Grant: Operating Grant

MAP kinases are a family of enzymes that play important roles in the control of cell proliferation and survival. Accumulating evidence suggests that these enzymes may be implicated in the pathogenesis of cancer. Our laboratory has identified a novel pathway involving the MAP kinases ERK3 and ERK4 that controls the progression through the different steps of the cell division cycle. Recent results suggest that ERK3 and ERK4 may exert tumor suppressor effect by braking cell proliferation and preventing the propagation of genetic errors. The objective of our project is to characterize the molecular mechanisms by which these enzymes control cell division and evaluate their putative involvement in the pathogenesis of cancer. To this end, we have generated transgenic mouse models bearing inactivating mutations in the ERK3 and ERK4 genes. The knowledge gained from these studies should prove useful for the identification of new and more selective targets for the design of anti-cancer agents.