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Mol Cell Biol, July 1998, p. 3974-3982, Vol. 18, No. 7
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

The Mdm2 Oncoprotein Interacts with the Cell Fate Regulator Numb

Tamar Juven-Gershon, Ohad Shifman, Tamar Unger, Adi Elkeles, Ygal Haupt,dagger and Moshe Oren*

Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel

Received 17 December 1997/Returned for modification 5 February 1998/Accepted 21 April 1998

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.

* Corresponding author. Mailing address: Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel. Phone: (972)-8-9342358. Fax: (972)-8-9465223. E-mail: lioren{at}dapsasl1.weizmann.ac.il.

dagger Present address: Lautenberg Center for General and Tumor Immunology, The Hebrew University Haddassah Medical School, Jerusalem 91120, Israel.

Mol Cell Biol, July 1998, p. 3974-3982, Vol. 18, No. 7
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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