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Control of iron homeostasis by an iron-regulated ubiquitin ligase.

Science (New York, N.Y.) | Oct 30, 2009

Eukaryotic cells require iron for survival and have developed regulatory mechanisms for maintaining appropriate intracellular iron concentrations. The degradation of iron regulatory protein 2 (IRP2) in iron-replete cells is a key event in this pathway, but the E3 ubiquitin ligase responsible for its proteolysis has remained elusive. We found that a SKP1-CUL1-FBXL5 ubiquitin ligase protein complex associates with and promotes the iron-dependent ubiquitination and degradation of IRP2. The F-box substrate adaptor protein FBXL5 was degraded upon iron and oxygen depletion in a process that required an iron-binding hemerythrin-like domain in its N terminus. Thus, iron homeostasis is regulated by a proteolytic pathway that couples IRP2 degradation to intracellular iron levels through the stability and activity of FBXL5.

Pubmed ID: 19762596 RIS Download

Mesh terms: Cell Line | Cullin Proteins | F-Box Proteins | Hemerythrin | Homeostasis | Humans | Iron | Iron Regulatory Protein 1 | Iron Regulatory Protein 2 | Oxygen | Protein Structure, Tertiary | Recombinant Proteins | SKP Cullin F-Box Protein Ligases | Ubiquitin-Protein Ligase Complexes | Ubiquitin-Protein Ligases

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Associated grants

  • Agency: NIGMS NIH HHS, Id: R01 GM045201
  • Agency: NIGMS NIH HHS, Id: R01 GM089778-01A1
  • Agency: NIGMS NIH HHS, Id: R01 GM045201-17
  • Agency: NIGMS NIH HHS, Id: GM45201
  • Agency: NIGMS NIH HHS, Id: R01 GM089778

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