Toggle Main Menu Toggle Search

Open Access padlockePrints

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

Downloads

Full text for this publication is not currently held within this repository. Alternative links are provided below where available.


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


Altmetrics

Altmetrics provided by Altmetric


Funding

Funder referenceFunder name
G120/817Medical Research Council

Share