Author: ["Koji Yamanaka","Haruto Ishikawa","Yuzuru Megumi","Fuminori Tokunaga","Masato Kanie","Tracey A. Rouault","Isao Morishima","Nagahiro Minato","Koichiro Ishimori","Kazuhiro Iwai"]
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Abstract
The ubiquitin system is involved in several basic cellular functions1,2,3. 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 motifs1,2,3. Although RING finger proteins constitute an important family of E3 ligases4, only a few post-transcriptional modifications, including phosphorylation1, proline hydroxylation5,6 and glycosylation7, 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 degradation8. 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.Cite this article
Yamanaka, K., Ishikawa, H., Megumi, Y. et al. Identification of the ubiquitin–protein ligase that recognizes oxidized IRP2. Nat Cell Biol 5, 336–340 (2003). https://doi.org/10.1038/ncb952 