https://scholars.lib.ntu.edu.tw/handle/123456789/473372
標題: | Loss of the Oxidative Stress Sensor NPGPx Compromises GRP78 Chaperone Activity and Induces Systemic Disease | 作者: | Wei P.-C. Hsieh Y.-H. Su M.-I. Jiang X. Hsu P.-H. Lo W.-T. Weng J.-Y. YUNG-MING JENG Wang J.-M. Chen P.-L. YI-CHENG CHANG Lee K.-F. Tsai M.-D. Shew J.-Y. Lee W.-H. |
公開日期: | 2012 | 卷: | 48 | 期: | 5 | 起(迄)頁: | 747-759 | 來源出版物: | Molecular Cell | 摘要: | NPGPx is a member of the glutathione peroxidase (GPx) family; however, it lacks GPx enzymatic activity due to the absence of a critical selenocysteine residue, rendering its function an enigma. Here, we show that NPGPx is a newly identified stress sensor that transmits oxidative stress signals by forming the disulfide bond between its Cys57 and Cys86 residues. This oxidized form of NPGPx binds to glucose-regulated protein (GRP)78 and forms covalent bonding intermediates between Cys86 of NPGPx and Cys41/Cys420 of GRP78. Subsequently, the formation of the disulfide bond between Cys41 and Cys420 of GRP78 enhances its chaperone activity. NPGPx-deficient cells display increased reactive oxygen species, accumulated misfolded proteins, and impaired GRP78 chaperone activity. Complete loss of NPGPx in animals causes systemic oxidative stress, increases carcinogenesis, and shortens life span. These results suggest that NPGPx is essential for releasing excessive ER stress by enhancing GRP78 chaperone activity to maintain physiological homeostasis. ? 2012 Elsevier Inc. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84870877138&doi=10.1016%2fj.molcel.2012.10.007&partnerID=40&md5=9796c4a87e6c51a24604baa840af473d https://scholars.lib.ntu.edu.tw/handle/123456789/473372 |
ISSN: | 1097-2765 | DOI: | 10.1016/j.molcel.2012.10.007 | SDG/關鍵字: | chaperone; disulfide; glucose regulated protein 78; glutathione peroxidase; NPGPx protein; reactive oxygen metabolite; unclassified drug; animal cell; animal experiment; animal tissue; article; carcinogenesis; controlled study; covalent bond; endoplasmic reticulum; lifespan; mouse; nonhuman; oxidative stress; Animals; Carrier Proteins; Cell Line, Tumor; Cell Proliferation; Cell Survival; Cell Transformation, Neoplastic; Cysteine; Disulfides; DNA Damage; Dose-Response Relationship, Drug; Endoplasmic Reticulum Stress; Fibroblasts; Heat-Shock Proteins; Homeostasis; Humans; Mice; Mice, Inbred C57BL; Mice, Knockout; Mutagenesis, Site-Directed; Mutation; Oxidants; Oxidation-Reduction; Oxidative Stress; Peroxidases; Protein Binding; Protein Folding; Proteostasis Deficiencies; Reactive Oxygen Species; Signal Transduction; Time Factors; Transfection; Animalia |
顯示於: | 病理學科所 |
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