C-terminal truncation of the peroxiredoxin Tpx1 decreases its sensitivity for hydrogen peroxide without compromising its role in signal transduction

• Published in: Genes to cells : devoted to molecular & cellular mechanisms Vol. 13; no. 2; pp. 171 - 179
• Main Authors: Jara, Mónica, Vivancos, Ana P, Hidalgo, Elena
• Format: Journal Article
• Language: English
• Published: Malden, USA Malden, USA : Blackwell Publishing Inc 01.02.2008; Blackwell Publishing Inc
• Subjects: Aerobiosis; Basic-Leucine Zipper Transcription Factors - genetics; Basic-Leucine Zipper Transcription Factors - metabolism; Gene Expression; Hydrogen Peroxide - metabolism; Hydrogen Peroxide - pharmacology; Kinetics; Mitogen-Activated Protein Kinases - genetics; Mitogen-Activated Protein Kinases - metabolism; Oxidative Stress; Peroxiredoxins - antagonists & inhibitors; Peroxiredoxins - chemistry; Peroxiredoxins - genetics; Peroxiredoxins - metabolism; Protein Structure, Tertiary; Recombinant Proteins - chemistry; Recombinant Proteins - genetics; Recombinant Proteins - metabolism; Schizosaccharomyces - genetics; Schizosaccharomyces - metabolism; Schizosaccharomyces pombe Proteins - antagonists & inhibitors; Schizosaccharomyces pombe Proteins - chemistry; Schizosaccharomyces pombe Proteins - genetics; Schizosaccharomyces pombe Proteins - metabolism; Sequence Deletion; Signal Transduction; Sulfinic Acids - metabolism
• ISSN: 1356-9597; 1365-2443
• DOI: 10.1111/j.1365-2443.2007.01160.x

Peroxiredoxins (Prxs) participate in hydrogen peroxide (H₂O₂) scavenging. Eukaryotic Prxs suffer H₂O₂-dependent inactivation, due to the oxidation of its catalytic cysteine to sulfinic acid, a modification which can be enzymatically reversed. This substrate-mediated reversible inactivation has been suggested to allow eukaryotic Prxs to act as floodgates, permitting high levels of H₂O₂ to trigger signal transduction. To test this hypothesis, we used the fission yeast Prx Tpx1, which acts as a H₂O₂ scavenger during aerobic metabolism and also participates in peroxide-induced signal transduction pathways. High concentrations of peroxide reversibly inactivate Tpx1.Here, we describe the characterization of a Tpx1 derivative, which lacks a carboxy-terminal extension present only in eukaryotic Prxs. This mutant protein is not inactivated by high doses of H₂O₂. Exclusive expression of this truncated version of Tpx1 is deleterious for aerobic growth, but H₂O₂-dependent signal transduction is not impaired in this strain. Instead, the ability of Tpx1.ΔCTD to detect and detoxify peroxides is impaired. Our results indicate that inactivation of Tpx1 by excess peroxides is not required for H₂O₂ signaling towards the Sty1 pathway, as expected from the floodgate model, and that the carboxy-terminal extension of Tpx1 concomitantly improves H₂O₂ scavenging and increases susceptibility to inactivation.