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Science. 2009 Oct 30;326(5953):718-21. doi: 10.1126/science.1176333. Epub 2009 Sep 17.

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

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  • 1Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.

Abstract

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.

PMID:
19762596
[PubMed - indexed for MEDLINE]
PMCID:
PMC2929180
Free PMC Article
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