铁调节蛋白2（IRP2）的S-亚硝基化通过泛素-蛋白酶体途径调节其稳定性。
S-nitrosylation of IRP2 regulates its stability via the ubiquitin-proteasome pathway.
作者信息
Kim Sangwon, Wing Simon S, Ponka Prem
机构信息
Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec H3T 1E2, Canada.
出版信息
Mol Cell Biol. 2004 Jan;24(1):330-7. doi: 10.1128/MCB.24.1.330-337.2004.
Abstract
Nitric oxide (NO) is an important signaling molecule that interacts with different targets depending on its redox state. NO can interact with thiol groups resulting in S-nitrosylation of proteins, but the functional implications of this modification are not yet fully understood. We have reported that treatment of RAW 264.7 cells with NO caused a decrease in levels of iron regulatory protein 2 (IRP2), which binds to iron-responsive elements present in untranslated regions of mRNAs for several proteins involved in iron metabolism. In this study, we show that NO causes S-nitrosylation of IRP2, both in vitro and in vivo, and this modification leads to IRP2 ubiquitination followed by its degradation in the proteasome. Moreover, mutation of one cysteine (C178S) prevents NO-mediated degradation of IRP2. Hence, S-nitrosylation is a novel signal for IRP2 degradation via the ubiquitin-proteasome pathway.
摘要
一氧化氮（NO）是一种重要的信号分子，它根据其氧化还原状态与不同的靶点相互作用。NO可与硫醇基团相互作用，导致蛋白质的S-亚硝基化，但这种修饰的功能意义尚未完全明确。我们曾报道，用NO处理RAW 264.7细胞会导致铁调节蛋白2（IRP2）水平降低，IRP2可与参与铁代谢的几种蛋白质的mRNA非翻译区中存在的铁反应元件结合。在本研究中，我们发现NO在体外和体内均会导致IRP2的S-亚硝基化，这种修饰会导致IRP2泛素化，随后在蛋白酶体中降解。此外，一个半胱氨酸（C178S）突变可阻止NO介导的IRP2降解。因此，S-亚硝基化是通过泛素-蛋白酶体途径降解IRP2的一种新信号。
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本文引用的文献
1
S-nitrosylation in health and disease.健康与疾病中的S-亚硝基化
Trends Mol Med. 2003 Apr;9(4):160-8. doi: 10.1016/s1471-4914(03)00028-5.
2
Identification of the ubiquitin-protein ligase that recognizes oxidized IRP2.识别识别氧化型铁调节蛋白2的泛素蛋白连接酶。
Nat Cell Biol. 2003 Apr;5(4):336-40. doi: 10.1038/ncb952.
3
Nitrogen monoxide-mediated control of ferritin synthesis: implications for macrophage iron homeostasis.一氧化氮介导的铁蛋白合成调控：对巨噬细胞铁稳态的影响
Proc Natl Acad Sci U S A. 2002 Sep 17;99(19):12214-9. doi: 10.1073/pnas.192316099. Epub 2002 Sep 3.
4
Basal and stimulated protein S-nitrosylation in multiple cell types and tissues.多种细胞类型和组织中的基础和刺激型蛋白S-亚硝基化
J Biol Chem. 2002 Mar 22;277(12):9637-40. doi: 10.1074/jbc.C100746200. Epub 2002 Jan 16.
5
Inhibition of NF-kappa B by S-nitrosylation.通过S-亚硝基化抑制核因子κB
Biochemistry. 2001 Feb 13;40(6):1688-93. doi: 10.1021/bi002239y.
6
HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing.脯氨酸羟化作用使HIFα靶向VHL介导的降解：对氧感知的影响
Science. 2001 Apr 20;292(5516):464-8. doi: 10.1126/science.1059817. Epub 2001 Apr 5.
7
Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation.通过氧调节的脯氨酰羟化作用将缺氧诱导因子-α靶向至希佩尔-林道泛素化复合体
Science. 2001 Apr 20;292(5516):468-72. doi: 10.1126/science.1059796. Epub 2001 Apr 5.
8
Targeted deletion of the gene encoding iron regulatory protein-2 causes misregulation of iron metabolism and neurodegenerative disease in mice.靶向缺失编码铁调节蛋白-2的基因会导致小鼠铁代谢失调和神经退行性疾病。
Nat Genet. 2001 Feb;27(2):209-14. doi: 10.1038/84859.
9
Protein S-nitrosylation: a physiological signal for neuronal nitric oxide.蛋白质S-亚硝基化：神经元一氧化氮的一种生理信号。
Nat Cell Biol. 2001 Feb;3(2):193-7. doi: 10.1038/35055104.
10
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Annu Rev Nutr. 2000;20:627-62. doi: 10.1146/annurev.nutr.20.1.627.
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