Juven-Gershon T, Shifman O, Unger T, Elkeles A, Haupt Y, Oren M
Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel.
Mol Cell Biol. 1998 Jul;18(7):3974-82. doi: 10.1128/MCB.18.7.3974.
The Mdm2 oncoprotein is a well-known inhibitor of the p53 tumor suppressor, but it may also possess p53-independent activities. In search of such p53-independent activities, the yeast two-hybrid screen was employed to identify Mdm2-binding proteins. We report that in vitro and in transfected cells, Mdm2 can associate with Numb, a protein involved in the determination of cell fate. This association causes translocation of overexpressed Numb into the nucleus and leads to a reduction in overall cellular Numb levels. Through its interaction with Numb, Mdm2 may influence processes such as differentiation and survival. This could potentially contribute to the altered properties of tumor cells which overexpress Mdm2.
Mdm2癌蛋白是一种众所周知的p53肿瘤抑制因子的抑制剂,但它也可能具有不依赖p53的活性。为了寻找这种不依赖p53的活性,我们利用酵母双杂交筛选来鉴定与Mdm2结合的蛋白。我们报道,在体外和转染细胞中,Mdm2可与Numb结合,Numb是一种参与细胞命运决定的蛋白。这种结合导致过表达的Numb易位至细胞核,并导致细胞内Numb总体水平降低。通过与Numb相互作用,Mdm2可能影响细胞分化和存活等过程。这可能潜在地导致过表达Mdm2的肿瘤细胞特性发生改变。