Thioredoxin-interacting Protein (Txnip) Is a Feedback Regulator of S-Nitrosylation
Thioredoxin-interacting Protein (Txnip) Is a Feedback Regulator of S-Nitrosylation
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DOI：
10.1074/jbc.m109.057729
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发表时间：
2009-12-25
影响因子：
4.8
通讯作者：
Stamler, Jonathan S.
中科院分区：
文献类型：
--
作者：
Forrester, Michael T.;Seth, Divya;Stamler, Jonathan S.
一氧化氮通过蛋白质S-亚硝基化（将蛋白质Cys硫醇转化为S-亚硝基硫醇的基于氧化还原的反应）发挥过多的生物效应。然而，尽管蛋白质S-亚硝基化的调控一直是广泛研究的主题，但对蛋白质脱亚硝基化的调控系统知之甚少。最近，硫氧还蛋白/硫氧还蛋白还原酶被证明介导基础和刺激偶联蛋白脱亚硝基化。我们现在证明，蛋白质脱亚硝基硫氧还蛋白的硫氧还蛋白相互作用蛋白（Txnip），硫氧还蛋白抑制剂的动态调节。内源性合成的一氧化氮抑制Txnip，从而促进硫氧还蛋白介导的脱亚硝基化。因此，脱亚硝基化的自动调节允许细胞在亚硝化应激中存活。我们的研究结果表明，蛋白质的去亚硝基化是动态调节的，硫氧还蛋白在保护亚硝化应激中的生理作用，并提出了操纵细胞S-亚硝基化的新方法。
Nitric oxide exerts a plethora of biological effects via protein S-nitrosylation, a redox-based reaction that converts a protein Cys thiol to a S-nitrosothiol. However, although the regulation of protein S-nitrosylation has been the subject of extensive study, much less is known about the systems governing protein denitrosylation. Most recently, thioredoxin/thioredoxin reductases were shown to mediate both basal and stimulus-coupled protein denitrosylation. We now demonstrate that protein denitrosylation by thioredoxin is regulated dynamically by thioredoxin-interacting protein (Txnip), a thioredoxin inhibitor. Endogenously synthesized nitric oxide represses Txnip, thereby facilitating thioredoxin-mediated denitrosylation. Autoregulation of denitrosylation thus allows cells to survive nitrosative stress. Our findings reveal that denitrosylation of proteins is dynamically regulated, establish a physiological role for thioredoxin in protection from nitrosative stress, and suggest new approaches to manipulate cellular S-nitrosylation.