Abstract
The protein encoded by the c-MYC proto-oncogene is a transcription factor that can both activate and repress the expression of target genes, but few of its transcriptional targets have been identified. Here, c-MYC is shown to repress the expression of the heavy subunit of the protein ferritin (H-ferritin), which sequesters intracellular iron, and to stimulate the expression of the iron regulatory protein-2 (IRP2), which increases the intracellular iron pool. Down-regulation of the expression of H-ferritin gene was required for cell transformation by c-MYC. These results indicate that c-MYC coordinately regulates genes controlling intracellular iron concentrations and that this function is essential for the control of cell proliferation and transformation by c-MYC.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Cell Division
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Cell Line
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Cell Line, Transformed
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Cell Transformation, Neoplastic
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DNA / biosynthesis
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Down-Regulation
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Ferritins / genetics*
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Ferritins / metabolism
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Gene Expression Regulation*
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Genes, myc
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Homeostasis
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Iron / metabolism*
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Iron Regulatory Protein 2
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Iron-Regulatory Proteins
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Iron-Sulfur Proteins / genetics*
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Iron-Sulfur Proteins / metabolism
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Proto-Oncogene Proteins c-myc / physiology*
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RNA / metabolism
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RNA-Binding Proteins / genetics*
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RNA-Binding Proteins / metabolism
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Receptors, Transferrin / genetics
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Transcription, Genetic
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Transfection
Substances
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Iron-Regulatory Proteins
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Iron-Sulfur Proteins
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Proto-Oncogene Proteins c-myc
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RNA-Binding Proteins
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Receptors, Transferrin
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RNA
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DNA
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Ferritins
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Iron
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Iron Regulatory Protein 2