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PMID: 7686617 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Mapping of the p53 and mdm-2 interaction domains.

Molecular and cellular biology ·Vol. 13 ·No. 7 ·1993-07-00 ·Pages 4107-14

Chen J, Marechal V, Levine AJ

Abstract

The 90-kDa cellular protein encoded by the mouse mdm-2 oncogene binds to the p53 protein in vivo and inhibits its transactivation function (J. Momand, G. P. Zambetti, D. C. Olson, D. George, and A. J. Levine, Cell 69:1237-1245, 1992). cDNA clones encoding the human homolog of the mdm-2 protein (also called hdm-2) were isolated from a HeLa cell cDNA library. A series of monoclonal antibodies have been generated against human mdm-2 protein, and the epitopes recognized by these antibodies have been mapped. By construction of a series of deletion mutants, the region of the mdm-2 protein that is critical for complex formation with the p53 protein has been mapped to the N-terminal portion of the human mdm-2 protein. Interestingly, a monoclonal antibody with an epitope located in this same region failed to immunoprecipitate the mdm-2-p53 complex and appeared to recognize only free mdm-2 protein. The domain of the p53 protein that is sufficient for interaction with human mdm-2 protein has been mapped to the N-terminal 52 amino acid residues of the p53 protein. This region contains the transactivation domain of p53, suggesting that mdm-2 may inhibit p53 function by disrupting its interaction with the general transcription machinery.

Related Genes
mdm-2
MeSH Terms
Animals Antibodies, Monoclonal Base Sequence Binding Sites DNA/isolation & purification Electrophoresis, Polyacrylamide Gel Epitopes HeLa Cells Humans Mice Molecular Sequence Data Neoplasm Proteins/genetics,metabolism Nuclear Proteins Oncogenes Proto-Oncogene Proteins Proto-Oncogene Proteins c-mdm2 Tumor Suppressor Protein p53/genetics,metabolism
Chemicals
Antibodies, Monoclonal Epitopes Neoplasm Proteins Nuclear Proteins Proto-Oncogene Proteins Tumor Suppressor Protein p53 DNA MDM2 protein, human Mdm2 protein, mouse Proto-Oncogene Proteins c-mdm2
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Chen J
Department of Molecular Biology, Princeton University, New Jersey 08544-1014.
Marechal V
Levine A J
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46 references, click to expand
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/mcb.13.7.4107-4114.1993
Published
1993-07-00
Pages
4107-14
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC359960
Subset
IM
Grants
NCI NIH HHS · CA41086 · United States
External Links
PubMed source DOI: 10.1128/mcb.13.7.4107-4114.1993 PMC Full Text View journal details
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