Thiol-based redox switches in eukaryotic proteins.
Thiol-based redox switches in eukaryotic proteins.
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DOI：
10.1089/ars.2008.2285
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发表时间：
2009-05
影响因子：
6.6
通讯作者：
Jakob U
中科院分区：
文献类型：
--
作者：
Brandes N;Schmitt S;Jakob U
多年来，胞质蛋白中的氧化巯基修饰在很大程度上被忽视为体外人工产物，并且被认为不太可能在细胞的还原环境中发挥重要作用。在体内巯基捕获技术结合质谱分析的最新发展，现在提供了令人信服的证据，巯基为基础的氧化还原开关被用作分子工具，在许多蛋白质，以调节其活性，反应活性氧和氮物种。已经发现可逆的氧化巯基修饰调节参与许多不同途径的蛋白质的功能，从基因转录、翻译和蛋白质折叠开始，到代谢、信号转导和最终凋亡。这篇综述将集中在三个特点鲜明的真核生物蛋白质，使用巯基为基础的氧化还原开关，影响基因转录，代谢和信号转导。转录因子Yap 1 p很好地说明了氧化修饰如何影响蛋白质的功能而不改变其活性。我们使用乙醛-3-磷酸脱氢酶来证明活性位点半胱氨酸的巯基修饰如何改变代谢途径并将代谢酶转化为促凋亡因子。最后，我们介绍了氧化还原敏感的蛋白酪氨酸磷酸酶PTP 1B，以说明可逆性是氧化还原调节的基本方面之一。
For many years, oxidative thiol modifications in cytosolic proteins were largely disregarded as in vitro artifacts, and considered unlikely to play significant roles within the reducing environment of the cell. Recent developments in in vivo thiol trapping technology combined with mass spectrometric analysis have now provided convincing evidence that thiol-based redox switches are used as molecular tools in many proteins to regulate their activity in response to reactive oxygen and nitrogen species. Reversible oxidative thiol modifications have been found to modulate the function of proteins involved in many different pathways, starting from gene transcription, translation and protein folding, to metabolism, signal transduction, and ultimately apoptosis. This review will focus on three well-characterized eukaryotic proteins that use thiol-based redox switches to influence gene transcription, metabolism, and signal transduction. The transcription factor Yap1p is a good illustration of how oxidative modifications affect the function of a protein without changing its activity. We use glyeraldehyde-3-phosphate dehydrogenase to demonstrate how thiol modification of an active site cysteine re-routes metabolic pathways and converts a metabolic enzyme into a pro-apoptotic factor. Finally, we introduce the redox-sensitive protein tyrosine phosphatase PTP1B to illustrate that reversibility is one of the fundamental aspects of redox-regulation.
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