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PMID:9924025

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Citation

Wu, KJ, Polack, A and Dalla-Favera, R (1999) Coordinated regulation of iron-controlling genes, H-ferritin and IRP2, by c-MYC. Science 283:676-9

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.

Links

PubMed

Keywords

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

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:MYC

involved_in

GO:0000122: negative regulation of transcription by RNA polymerase II

ECO:0000314: direct assay evidence used in manual assertion

P

  • has_input:(UniProtKB:P02794)

Seeded From UniProt

complete

HUMAN:MYC

involved_in

GO:0045944: positive regulation of transcription by RNA polymerase II

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • has_input:(UniProtKB:P48200)

Seeded From UniProt

complete

RAT:MYC

involved_in

GO:0000122: negative regulation of transcription by RNA polymerase II

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • has_input:(UniProtKB:P19132)

Seeded From UniProt

complete

RAT:FRIH

involved_in

GO:0048147: negative regulation of fibroblast proliferation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:IREB2

involved_in

GO:0006826: iron ion transport

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:IREB2

enables

GO:0030350: iron-responsive element binding

ECO:0000304: author statement supported by traceable reference used in manual assertion

F

Seeded From UniProt

complete

HUMAN:IREB2

enables

GO:0003723: RNA binding

ECO:0000304: author statement supported by traceable reference used in manual assertion

F

Seeded From UniProt

complete

HUMAN:FRIH

involved_in

GO:0048147: negative regulation of fibroblast proliferation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:FRIH

involved_in

GO:0006880: intracellular sequestering of iron ion

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:MYC

involved_in

GO:0000122: negative regulation of transcription by RNA polymerase II

ECO:0000314: direct assay evidence used in manual assertion

P

has_regulation_target:(UniProtKB:P02794)

Seeded From UniProt

complete

HUMAN:MYC

involved_in

GO:2000573: positive regulation of DNA biosynthetic process

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:MYC

involved_in

GO:0048146: positive regulation of fibroblast proliferation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:MYC

involved_in

GO:0045944: positive regulation of transcription by RNA polymerase II

ECO:0000315: mutant phenotype evidence used in manual assertion

P

has_regulation_target:(UniProtKB:P48200)

Seeded From UniProt

complete

HUMAN:MYC

involved_in

GO:0045656: negative regulation of monocyte differentiation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:MYC

involved_in

GO:0015671: oxygen transport

ECO:0000303: author statement without traceable support used in manual assertion

P

Seeded From UniProt

complete

HUMAN:MYC

involved_in

GO:0006879: cellular iron ion homeostasis

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:MYC

involved_in

GO:0006112: energy reserve metabolic process

ECO:0000303: author statement without traceable support used in manual assertion

P

Seeded From UniProt

complete

HUMAN:MYC

enables

GO:0003700: DNA-binding transcription factor activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete


See also

References

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