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

Lookup NU author(s): Dr Elizabeth Veal, Victoria Findlay, Dr Alison Day, Stephanie Bozonet, Professor Janet Quinn, Professor Brian Morgan

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Abstract

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 peroxideinduced 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.

Publication metadata

Author(s): Veal EA, Findlay VJ, Day AM, Bozonet SM, Evans JM, Quinn J, Morgan BA

Publication type: Article

Publication status: Published

Journal: Molecular Cell

Year: 2004

Volume: 15

Issue: 1

Pages: 129-139

ISSN (print): 1097-2765

ISSN (electronic): 1097-4164

Publisher: Cell Press

URL: http://dx.doi.org/10.1016/j.molcel.2004.06.021

DOI: 10.1016/j.molcel.2004.06.021

PubMed id: 15225554

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