Coordinated regulation of iron-controlling genes, H-ferritin and IRP2, by c-MYC

Science. 1999 Jan 29;283(5402):676-9. doi: 10.1126/science.283.5402.676.


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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Division
  • Cell Line
  • Cell Line, Transformed
  • Cell Transformation, Neoplastic
  • DNA / biosynthesis
  • Down-Regulation
  • Ferritins / genetics*
  • Ferritins / metabolism
  • Gene Expression Regulation*
  • Genes, myc
  • Homeostasis
  • Iron / metabolism*
  • Iron Regulatory Protein 2
  • Iron-Regulatory Proteins
  • Iron-Sulfur Proteins / genetics*
  • Iron-Sulfur Proteins / metabolism
  • Proto-Oncogene Proteins c-myc / physiology*
  • RNA / metabolism
  • RNA-Binding Proteins / genetics*
  • RNA-Binding Proteins / metabolism
  • Receptors, Transferrin / genetics
  • Transcription, Genetic
  • Transfection


  • Iron-Regulatory Proteins
  • Iron-Sulfur Proteins
  • Proto-Oncogene Proteins c-myc
  • RNA-Binding Proteins
  • Receptors, Transferrin
  • RNA
  • DNA
  • Ferritins
  • Iron
  • Iron Regulatory Protein 2