THE MDM2 ONCOPROTEIN INTERACTS WITH THE CELL FATE REGULATOR NUMB

The Mdm2 oncoprotein is a well-known inhibitor of the p53 tumor suppre ssor, but it may also possess p53-independent activities. In search of such p53-independent activities, the yeast two-hybrid screen was empl oyed to identify Mdm2-binding proteins. We report that in vitro and in transfected cells, Mdm2 can associate with Numb, a protein involved i n the determination of cell fate. This association causes translocatio n of overexpressed Numb into the nucleus and leads to a reduction in o verall cellular Numb levels. Through its interaction with Numb, Mdm2 m ay influence processes such as differentiation and survival. This coul d potentially contribute to the altered properties of tumor cells whic h overexpress Mdm2.