A 2-Cys peroxiredoxin regulates peroxide-induced oxidation and activation of a stress-activated MAP kinase

被引：173

作者：

Veal, EA ^{[1
]}

Findlay, VJ ^{[1
]}

Day, AM ^{[1
]}

Bozonet, SM ^{[1
]}

Evans, JM ^{[1
]}

Quinn, J ^{[1
]}

Morgan, BA ^{[1
]}

机构：

[1] Newcastle Univ, Fac Med Sci, Inst Cell & Mol Biosci, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England

来源：

MOLECULAR CELL | 2004年 / 15卷 / 01期

基金：

英国医学研究理事会;

关键词：

D O I：

10.1016/j.molcel.2004.06.021

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Oxidative stress-induced cell damage is an important component of many diseases and ageing. In eukaryotes, activation of JNK/p38 stress-activated protein kinase (SAPK) signaling pathways is critical for the cellular response to stress. 2-Cys; peroxiredoxins (2-Cys Prx) are highly conserved, extremely abundant antioxidant enzymes that catalyze the breakdown of peroxides to protect cells from oxidative stress. Here we reveal that Tpx1, the single 2-Cys Prx in Schizosaccharomyces pombe, is required for the peroxide-induced activation of the p38/JNK homolog, Sty1. Tpx1 activates Sty1, downstream of previously identified redox sensors, by a mechanism that involves formation of a peroxide-induced disulphide complex between Tpx1 and Sty1. We have identified conserved cysteines in Tpx1 and Sty1 that are essential for normal peroxide-induced Tpx1-Sty1 disulphide formation and Tpx1-dependent regulation of peroxide-induced Sty1 activation. Thus we provide new insight into the response of SAPKs to diverse stimuli by revealing a mechanism for SAPK activation specifically by oxidative stress.

引用

页码：129 / 139

页数：11

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[1] Regulation of JNK signaling by GSTp [J].