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Sci. STKE, 13 July 2004
Vol. 2004, Issue 241, p. tw246
[DOI: 10.1126/stke.2412004tw246]

OXIDATIVE STRESS Eukaryotic Redox Sensor

Cells use antioxidant enzymes to combat damaging oxidative stress, like that imposed by reactive oxygen species (ROS) such as H2O2. Eukaryotic cells also activate a JNK-p38-stress-activated protein kinase (SAPK) signaling pathway to induce specific gene expression in response to a variety of stress conditions. Just how cells activate this pathway in response to stress has not been clear. Veal et al. report that in the yeast Schizosaccharomyces pombe, a thioredoxin peroxidase called Tpx1 acts as a redox sensor that directly activates Sty1, the SAPK homolog, in response to H2O2. Exposure to peroxide induced the formation of a specific intermolecular disulfide bond between Tpx1 and Sty1 that activated Sty1 and the expression of downstream target genes. This effect was specific to oxidative stress and not osmotic stress. This signaling function of TPx1 was also preserved in a mutant that lacked enzymatic activity. A two-component signaling pathway that regulates the activity of a mitogen-activated protein kinase kinase called Wis1 has also been implicated in activating Sty1 in response to peroxides. Overexpression of Tpx1 in a mutant strain lacking Wis1 did not rescue Sty1 activation in response to H2O2, which indicates that the Tpx1-Sty1 signaling pathway requires Wis1. The family of thioredoxin peroxidases to which Tpx1 belongs is highly conserved in eukaryotes, which suggests that these proteins may be involved in redox sensing in mammalian cells.

E. A. Veal, V. J. Findlay, A. M. Day, S. M. Bozonet, J. M. Evans, J. Quinn, B. A. Morgan, A 2-Cys peroxiredoxin regulates peroxide-induced oxidation and activation of a stress-activated MAP kinase. Mol. Cell 15, 129-139 (2004). [Online Journal]

Citation: Eukaryotic Redox Sensor. Sci. STKE 2004, tw246 (2004).


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