Identification and characterization of multiple mdm-2 proteins and mdm-2-p53 protein complexes.

A protein product of the mdm-2 oncogene (p90) has been recently shown to associate with the protein encoded by the tumor-suppressor gene p53. The mdm-2 gene was originally identified as a gene amplified in a spontaneously transformed Balb/c 3T3 cell line (3T3DM). This report describes the characterization of mdm-2 gene ...
products and their interactions with the p53 protein. Polyclonal and monoclonal antibodies were generated against murine and human mdm-2 protein. These antibodies detected the mdm-2 p90 protein and at least four additional polypeptides (p85, p76, p74, p58-p57) in cultured cells. These additional proteins may arise from different spliced mRNA forms of the mdm-2 gene or post-translational modifications of the mdm-2 protein. The monoclonal antibodies distinguished at least three sets of mdm-2 proteins with distinct combinations of epitopes (p90 and p85; p76 and p74; p58-57). One or two of these proteins forms a complex with the p53 protein (p90, p58). These mdm-2 proteins were found to be overexpressed in 3T3DM cells and a subset of these proteins were complexed with p53. In 3T3DM cells, p90, like p53, had a short half-life of approximately 20 min and was localized to the cell nucleus. In resting cells stimulated with serum p90 levels and p90/p53 complex levels increased in the late G1 phase of the cell cycle. The p90 mdm-2 protein could regulate p53 activity in the late G1 phase of the cell cycle.
Mesh Terms:
Animals, Antibodies, Monoclonal, Cell Cycle, Cloning, Molecular, Epitopes, Humans, Macromolecular Substances, Mice, Neoplasm Proteins, Nuclear Proteins, Phosphoproteins, Protein Binding, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-mdm2, S Phase, Tumor Suppressor Protein p53, Zinc Fingers
Date: Sep. 01, 1993
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