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PMID: 9632782 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

The Mdm2 oncoprotein interacts with the cell fate regulator Numb.

Molecular and cellular biology ·Vol. 18 ·No. 7 ·1998-07-00 ·Pages 3974-82

Juven-Gershon T, Shifman O, Unger T, Elkeles A, Haupt Y, Oren M

Abstract

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.

MeSH Terms
Amino Acid Sequence Animals Binding Sites Cell Differentiation Cell Line Cell Line, Transformed Chemical Precipitation Humans Membrane Proteins/genetics,metabolism Molecular Sequence Data Nerve Tissue Proteins/genetics,metabolism Nuclear Proteins Proto-Oncogene Proteins/genetics,metabolism Proto-Oncogene Proteins c-mdm2 Rabbits Recombinant Fusion Proteins/genetics,metabolism Subcellular Fractions Tumor Cells, Cultured
Chemicals
Membrane Proteins Nerve Tissue Proteins Nuclear Proteins Numb protein, human Numb protein, mouse Proto-Oncogene Proteins Recombinant Fusion Proteins MDM2 protein, human Proto-Oncogene Proteins c-mdm2
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Juven-Gershon T
Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel.
Shifman O
Unger T
Elkeles A
Haupt Y
Oren M
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.18.7.3974
Published
1998-07-00
Pages
3974-82
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC108982
Subset
IM
Grants
NCI NIH HHS · R01 CA 40099 · United States
External Links
PubMed source DOI: 10.1128/MCB.18.7.3974 PMC Full Text View journal details
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