Identification of the ubiquitin-protein ligase that recognizes oxidized IRP2
Identification of the ubiquitin-protein ligase that recognizes oxidized IRP2
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DOI：
10.1038/ncb952
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发表时间：
2003-04-01
影响因子：
21.3
通讯作者：
Iwai, K
中科院分区：
文献类型：
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作者：
Yamanaka, K;Ishikawa, H;Iwai, K
泛素系统参与了几种基本的细胞功能(1-3)。泛素化是由EL、E2和E3酶催化的三个反应级联而成的。其中，E3泛素-蛋白连接酶通过定义的靶向基序(1-3)识别靶底物，在决定系统的特异性方面起着关键作用。虽然环指蛋白是E3连接酶的一个重要家族(4)，但只有少数转录后修饰，包括磷酸化(1)、脯氨酸羟化(5，6)和糖基化(7)，被认为是E3的识别信号。铁调节蛋白2(IRP2)是铁代谢的调节剂，受铁诱导的泛素化和降解调节(8)。在这里，我们显示了环指蛋白HOIL-1作为氧化IRP2的E3连接酶的功能，表明氧化是泛素化的特异性识别信号。IRP2的氧化是由血红素产生的，它与富铁细胞中的IRP2结合，并由氧产生，这表明IRP2的铁敏依赖于血红素的合成和可获得性。
The ubiquitin system is involved in several basic cellular functions(1-3). Ubiquitination is carried out by a cascade of three reactions catalysed by the El, 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(1-3). Although RING finger proteins constitute an important family of E3 ligases(4), only a few post-transcriptional modifications, including phosphorylation(1), proline hydroxylation(5,6) and glycosylation(7), 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(8). 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.