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Mol Cell Biol. Jul 1993; 13(7): 4107–4114.
PMCID: PMC359960

Mapping of the p53 and mdm-2 interaction domains.

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.

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Selected References

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