دورية أكاديمية
A conserved cysteine‐based redox mechanism sustains TFEB/HLH‐30 activity under persistent stress
| العنوان: | A conserved cysteine‐based redox mechanism sustains TFEB/HLH‐30 activity under persistent stress |
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| المؤلفون: | Martina, José A., Guerrero-Gómez, David, Gómez-Orte, Eva, Bárcena, J. Antonio, Cabello, Juan, Miranda-Vizuete, Antonio, Puertollano, Rosa |
| المساهمون: | National Institutes of Health (US), National Heart, Lung, and Blood Institute (US), Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), European Commission |
| بيانات النشر: | EMBO Press |
| سنة النشر: | 2021 |
| المجموعة: | Digital.CSIC (Consejo Superior de Investigaciones Científicas / Spanish National Research Council) |
| مصطلحات موضوعية: | Lutathionylation, HLH-30, Lysosomes, TFE3, TFEB |
| الوصف: | Mammalian TFEB and TFE3, as well as their ortholog in Caenorhabditis elegans HLH‐30, play an important role in mediating cellular response to a variety of stress conditions, including nutrient deprivation, oxidative stress, and pathogen infection. In this study, we identify a novel mechanism of TFEB/HLH‐30 regulation through a cysteine‐mediated redox switch. Under stress conditions, TFEB‐C212 undergoes oxidation, allowing the formation of intermolecular disulfide bonds that result in TFEB oligomerization. TFEB oligomers display increased resistance to mTORC1‐mediated inactivation and are more stable under prolonged stress conditions. Mutation of the only cysteine residue present in HLH‐30 (C284) significantly reduced its activity, resulting in developmental defects and increased pathogen susceptibility in worms. Therefore, cysteine oxidation represents a new type of TFEB post‐translational modification that functions as a molecular switch to link changes in redox balance with expression of TFEB/HLH‐30 target genes. ; Some C. elegans strains were provided by the CGC, which is funded by NIH Office of Research Infrastructure Programs (P40 OD010440). J.A.M. and R.P. were supported by the Intramural Research Program of the NIH, National Heart, Lung, and Blood Institute (NHLBI). E.G.O., D.G.G., J.C., and A.M.V. were supported by the Project PGC2018‐094276‐B‐I00 and JAB by the Project BFU2016‐80006‐P (both financed by the Spanish Ministerio de Ciencia, Innovación y Universidades (MCIU), the Spanish Agencia Estatal de Investigación (AEI), and the Fondo Europeo de Desarrollo Regional (FEDER). ; Peer reviewed |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | unknown |
| تدمد: | 0261-4189 |
| العلاقة: | #PLACEHOLDER_PARENT_METADATA_VALUE#; info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PGC2018‐094276‐B‐I00; info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/BFU2016‐80006‐P; Postprint; http://doi.org/10.15252/embj.2020105793Test; Sí; e-issn: 1460-2075; EMBO Journal 40(3): e105793 (2021); http://hdl.handle.net/10261/239614Test; http://dx.doi.org/10.13039/501100011033Test; http://dx.doi.org/10.13039/501100000780Test; http://dx.doi.org/10.13039/501100003329Test; http://dx.doi.org/10.13039/100000002Test |
| DOI: | 10.15252/embj.2020105793 |
| DOI: | 10.13039/501100011033 |
| DOI: | 10.13039/501100000780 |
| DOI: | 10.13039/501100003329 |
| DOI: | 10.13039/100000002 |
| الإتاحة: | https://doi.org/10.15252/embj.2020105793Test https://doi.org/10.13039/501100011033Test https://doi.org/10.13039/501100000780Test https://doi.org/10.13039/501100003329Test https://doi.org/10.13039/100000002Test http://hdl.handle.net/10261/239614Test |
| حقوق: | open |
| رقم الانضمام: | edsbas.BEE3A165 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 02614189 |
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| DOI: | 10.15252/embj.2020105793 |