The Mdm2 oncoprotein interacts with the cell fate regulator Numb.
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.
Juven-Gershon
T
T
Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel.
Shifman
O
O
Unger
T
T
Elkeles
A
A
Haupt
Y
Y
Oren
M
M
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002454:Cell Differentiation; D002460:Cell Line; D002461:Cell Line, Transformed; D011232:Chemical Precipitation; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D051736:Proto-Oncogene Proteins c-mdm2; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013347:Subcellular Fractions; D014407:Tumor Cells, Cultured
D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C113026:NUMB protein, human; C106293:Numb protein, mouse; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2