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

The protein encoded by the c-MYC proto-oncogene is a transcription factor t hat can both activate and repress the expression of target genes, but few o f its transcriptional targets have been identified. Here, c-MYC is shown to repress the expression of the heavy subunit of the protein ferritin (H-fer ritin), which sequesters intracellular iron, and to stimulate the expressio n of the iron regulatory protein-2 (IRP2), which increases the intracellula r iron pool. Downregulation of the expression of H-ferritin gene was requir ed for cell transformation by c-MYC. These results indicate that c-MYC coor dinately regulates genes controlling intracellular iron concentrations and that this function is essential for the control of cell proliferation and t ransformation by c-MYC.