Abstract
The alternative product of the human INK4a/ARF locus, p14ARF, has the potential to act as a tumour suppressor by binding to and inhibiting the p53 antagonist MDM2. Current models propose that ARF function depends on its ability to sequester MDM2 in the nucleolus. Here we describe situations in which stabilization of MDM2 and p53 occur without relocalization of endogenous MDM2 from the nucleoplasm. Conversely, forms of ARF that do not accumulate in the nucleolus retain the capacity to stabilize MDM2 and p53. We therefore propose that nucleolar localization is not essential for ARF function but may enhance the availability of ARF to inhibit MDM2.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Cell Nucleolus / metabolism*
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Cell Nucleus / metabolism
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Cells, Cultured
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Cytoplasm / metabolism
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Fibroblasts / metabolism
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Humans
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Immunoblotting
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Isopropyl Thiogalactoside / metabolism
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Microscopy, Fluorescence
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Nuclear Proteins*
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Plasmids / metabolism
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Precipitin Tests
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Promoter Regions, Genetic
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Proteins / metabolism*
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Proto-Oncogene Proteins / metabolism*
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Proto-Oncogene Proteins c-mdm2
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Retroviridae / genetics
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Subcellular Fractions / metabolism
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Time Factors
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Transfection
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Tumor Cells, Cultured
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Tumor Suppressor Protein p14ARF
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Tumor Suppressor Protein p53 / metabolism*
Substances
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Nuclear Proteins
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Proteins
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Proto-Oncogene Proteins
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Tumor Suppressor Protein p14ARF
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Tumor Suppressor Protein p53
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Isopropyl Thiogalactoside
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MDM2 protein, human
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Proto-Oncogene Proteins c-mdm2