Abstract
The ARF tumor suppressor protein acts in a checkpoint that guards against unscheduled cellular proliferation in response to oncogenic signaling. Deregulated expression of c-Myc induces ARF expression and apoptosis through the ARF-Mdm2-p53 axis. Our recent study reveals a new direct role for ARF in controlling c-Myc's oncogenic activity that is independent of p53. ARF binds to and selectively impairs the transactivation ability of c-Myc while leaving its transrepression ability intact. Biologically, ARF prevents hyper-proliferation and transformation caused by c-Myc and enhances c-Myc-induced apoptosis independently of p53. These new findings may be especially relevant for therapeutic strategies targeting c-Myc-induced cancers.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Apoptosis / genetics
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Cell Line
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Cell Proliferation*
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Cell Transformation, Neoplastic / genetics
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Cyclin-Dependent Kinase Inhibitor p16
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Gene Expression Regulation, Neoplastic
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Humans
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Mice
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Proto-Oncogene Proteins c-myc / genetics
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Proto-Oncogene Proteins c-myc / physiology*
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Signal Transduction / genetics
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Transcriptional Activation
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Tumor Suppressor Protein p14ARF / genetics
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Tumor Suppressor Protein p14ARF / physiology*
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Tumor Suppressor Protein p53 / genetics
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Tumor Suppressor Protein p53 / physiology
Substances
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Cdkn2a protein, mouse
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Cyclin-Dependent Kinase Inhibitor p16
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Proto-Oncogene Proteins c-myc
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Tumor Suppressor Protein p14ARF
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Tumor Suppressor Protein p53