Abstract
We isolated a 33-kDa protein, Pex19p/HK33/HsPXF, as a p19ARF-binding protein in a yeast two-hybrid screen. We demonstrate here that Pex19p interacts with p19ARF in the cell cytoplasm and excludes p19ARF from the nucleus, leading to a concurrent inactivation of p53 function. Down-regulation of Pex19p by its antisense expression resulted in increased levels of p19ARF, increased p53 function, and a p53/p21WAF1-mediated senescence-like cell cycle arrest. The data demonstrated a novel mechanism of down-regulation of the p19ARF-p53 pathway.
MeSH terms
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3T3 Cells
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Animals
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COS Cells
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Cell Cycle
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Cell Line
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Cell Nucleus / metabolism
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclins / metabolism*
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Cytoplasm / metabolism
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DNA, Complementary / metabolism
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Dose-Response Relationship, Drug
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Down-Regulation
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Genes, Reporter
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Genes, Tumor Suppressor*
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Haplorhini
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Membrane Proteins / metabolism*
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Membrane Proteins / physiology*
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Mice
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Oligonucleotides, Antisense / metabolism
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Phenotype
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Plasmids / metabolism
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Precipitin Tests
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Protein Binding
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Proteins / metabolism*
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Tumor Suppressor Protein p14ARF
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Tumor Suppressor Protein p53 / metabolism*
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Two-Hybrid System Techniques
Substances
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Cdkn1a protein, mouse
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclins
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DNA, Complementary
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Membrane Proteins
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Oligonucleotides, Antisense
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Proteins
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Tumor Suppressor Protein p14ARF
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Tumor Suppressor Protein p53