Control of protein function through oxidation and reduction of persulfidated states
| Autor: | Takaaki Akaike, Edward E. Schmidt, Justin R. Prigge, Elias S.J. Arnér, Tsuyoshi Takata, Tomoaki Ida, N. Balog, Yosuke Funato, Péter Nagy, Yoshito Kumagai, Qing Cheng, Hiroaki Miki, Yumi Abiko, Markus Dagnell, Éva Dóka, Akira Nishimura, Jon M. Fukuto, B. Espinosa, Nho Cong Luong |
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| Rok vydání: | 2020 |
| Předmět: |
Thioredoxin Reductase 1
medicine.medical_treatment Oxidative phosphorylation Sulfides Biochemistry Mice Selenium 03 medical and health sciences chemistry.chemical_compound Thioredoxins 0302 clinical medicine medicine Animals Humans Cysteine HSP90 Heat-Shock Proteins Research Articles 030304 developmental biology Homeodomain Proteins Protein Tyrosine Phosphatase Non-Receptor Type 1 0303 health sciences Gene knockdown Kelch-Like ECH-Associated Protein 1 Multidisciplinary Epidermal Growth Factor biology Chemistry Growth factor PTEN Phosphohydrolase SciAdv r-articles Glutathione KEAP1 Hsp90 Cell biology biology.protein Signal transduction Thioredoxin Oxidation-Reduction 030217 neurology & neurosurgery Signal Transduction Research Article |
| Zdroj: | Science Advances |
| ISSN: | 2375-2548 |
| DOI: | 10.1126/sciadv.aax8358 |
| Popis: | Thioredoxin system–mediated persulfidation of Cys residues controls protein function and protects them from oxidative stress. Irreversible oxidation of Cys residues to sulfinic/sulfonic forms typically impairs protein function. We found that persulfidation (CysSSH) protects Cys from irreversible oxidative loss of function by the formation of CysSSO1-3H derivatives that can subsequently be reduced back to native thiols. Reductive reactivation of oxidized persulfides by the thioredoxin system was demonstrated in albumin, Prx2, and PTP1B. In cells, this mechanism protects and regulates key proteins of signaling pathways, including Prx2, PTEN, PTP1B, HSP90, and KEAP1. Using quantitative mass spectrometry, we show that (i) CysSSH and CysSSO3H species are abundant in mouse liver and enzymatically regulated by the glutathione and thioredoxin systems and (ii) deletion of the thioredoxin-related protein TRP14 in mice altered CysSSH levels on a subset of proteins, predicting a role for TRP14 in persulfide signaling. Furthermore, selenium supplementation, polysulfide treatment, or knockdown of TRP14 mediated cellular responses to EGF, suggesting a role for TrxR1/TRP14-regulated oxidative persulfidation in growth factor responsiveness. |
| Databáze: | OpenAIRE |
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