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Nat Cell Biol. 2003 Apr;5(4):336-40.

Identification of the ubiquitin-protein ligase that recognizes oxidized IRP2.

Author information

1
Department of Molecular & System Biology, Graduate School of Biostudies, Kyoto University, Sakyo-Ku, Kyoto 606-8501, Japan.

Abstract

The ubiquitin system is involved in several basic cellular functions. Ubiquitination is carried out by a cascade of three reactions catalysed by the E1, E2 and E3 enzymes. Among these, the E3 ubiquitin-protein ligases have a pivotal role in determining the specificity of the system by recognizing the target substrates through defined targeting motifs. Although RING finger proteins constitute an important family of E3 ligases, only a few post-transcriptional modifications, including phosphorylation, proline hydroxylation and glycosylation, are known to function as recognition signals for E3. Iron regulatory protein 2 (IRP2), a modulator of iron metabolism, is regulated by iron-induced ubiquitination and degradation. Here we show that the RING finger protein HOIL-1 functions as an E3 ligase for oxidized IRP2, suggesting that oxidation is a specific recognition signal for ubiquitination. The oxidation of IRP2 is generated by haem, which binds to IRP2 in iron-rich cells, and by oxygen, indicating that the iron sensing of IRP2 depends on the synthesis and availability of haem.

PMID:
12629548
DOI:
10.1038/ncb952
[Indexed for MEDLINE]

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