Abstract
The mdm2 oncogene encodes a 90-kilodalton nuclear phosphoprotein that binds and inactivates the p53 tumor suppressor protein. Here we report the observation of five alternatively spliced mdm2 gene transcripts in a range of human cancers and their absence in normal tissues. Transfection of NIH 3T3 cells with each of these forms gave foci of morphologically transformed cells. A higher frequency of splice variants lacking p53 binding domain sequences was found in late-stage and high-grade ovarian and bladder carcinomas. Four of the splice variants show loss of p53 binding, consistent with partial deletion of sequences encoding the p53 binding domain, but retain carboxyterminal zinc-finger domains. These observations suggest a reassessment of the transforming mechanisms of mdm2 and its relation to p53.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3T3 Cells
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Alternative Splicing*
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Animals
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Base Sequence
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Cell Transformation, Neoplastic
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DNA Primers
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Disease Progression
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Female
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Humans
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Leukemia / metabolism
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Mice
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Molecular Sequence Data
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Neoplasm Proteins / genetics*
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Neoplasm Proteins / metabolism
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Nuclear Proteins*
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Ovarian Neoplasms / metabolism
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Ovarian Neoplasms / pathology
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Protein Binding
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Proto-Oncogene Proteins / genetics*
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-mdm2
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RNA / metabolism
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Transformation, Genetic
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Tumor Suppressor Protein p53 / metabolism*
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Urinary Bladder Neoplasms / metabolism
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Urinary Bladder Neoplasms / pathology
Substances
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DNA Primers
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Neoplasm Proteins
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Nuclear Proteins
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Proto-Oncogene Proteins
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Tumor Suppressor Protein p53
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RNA
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MDM2 protein, human
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Mdm2 protein, mouse
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Proto-Oncogene Proteins c-mdm2
Associated data
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GENBANK/U33199
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GENBANK/U33200
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GENBANK/U33201
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GENBANK/U33202
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GENBANK/U33203