論文 - 詳細
| RRC ID | 65343 |
|---|---|
| 著者 | Martina JA, Guerrero-Gómez D, Gómez-Orte E, Antonio Bárcena J, Cabello J, Miranda-Vizuete A, Puertollano R. |
| タイトル | A conserved cysteine-based redox mechanism sustains TFEB/HLH-30 activity under persistent stress. |
| ジャーナル | EMBO J |
| Abstract |
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. |
| 巻・号 | 40(3) |
| ページ | e105793 |
| 公開日 | 2021-2-1 |
| DOI | 10.15252/embj.2020105793 |
| PMID | 33314217 |
| PMC | PMC7849306 |
| MeSH | Animals Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / genetics Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / metabolism* Basic Helix-Loop-Helix Transcription Factors / genetics Basic Helix-Loop-Helix Transcription Factors / metabolism* Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Cell Line Cysteine HeLa Cells Humans Mice Mutation* Oxidation-Reduction Protein Multimerization Protein Processing, Post-Translational RAW 264.7 Cells |
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| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
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