A thiol peroxidase is an H2O2 receptor and redox-transducer in gene activation

被引:719
作者
Delaunay, A
Pflieger, D
Barrault, MB
Vinh, J
Toledano, MB [1 ]
机构
[1] CEA Saclay, Lab Stress Oxydants & Canc, SBGM, DBJC, F-91191 Gif Sur Yvette, France
[2] Ecole Super Phys & Chim Ind Ville Paris, CNRS, UMR 7637, Lab Neurobiol & Divers Cellulaire, F-75231 Paris, France
基金
澳大利亚研究理事会;
关键词
D O I
10.1016/S0092-8674(02)01048-6
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
The Yap1 transcription factor regulates hydroperoxide homeostasis in S. cerevisiae. Yap1 is activated by oxidation when hydroperoxide levels increase. We show that Yap1 is not directly oxidized by hydroperoxide. We identified the glutathione peroxidase (GPX)-like enzyme Gpx3 as a second component of the pathway, serving the role of sensor and transducer of the hydroperoxide signal to Yap1. When oxidized by H2O2, Gpx3 Cys36 bridges Yap1 Cys598 by a disulfide bond. This intermolecular disulfide bond is then resolved into a Yap1 intramolecular disulfide bond, the activated form of the regulator. Thioredoxin turns off the pathway by reducing both sensor and regulator. These data reveal a redox-signaling function for a GPx-like enzyme and elucidate a eukaryotic hydroperoxide-sensing mechanism. Gpx3 is thus a hydroperoxide receptor and redox-transducer.
引用
收藏
页码:471 / 481
页数:11
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