PXD022258 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | A conserved cysteine-based redox mechanism sustains TFEB/HLH-30 activity under persistent stress |
Description | Mammalian TFEB and TFE3, as well as their ortholog in C. 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. 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. |
HostingRepository | PRIDE |
AnnounceDate | 2021-01-22 |
AnnouncementXML | Submission_2021-01-21_23:48:12.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Jose Martina |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | phosphorylated residue; monohydroxylated residue; L-cysteine glutathione disulfide |
Instrument | Orbitrap Fusion Lumos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2020-10-30 02:26:44 | ID requested | |
⏵ 1 | 2021-01-21 23:48:13 | announced | |
Publication List
Martina JA, Guerrero-G, ó, mez D, G, ó, mez-Orte E, Antonio B, á, rcena J, Cabello J, Miranda-Vizuete A, Puertollano R, A conserved cysteine-based redox mechanism sustains TFEB/HLH-30 activity under persistent stress. EMBO J, 40(3):e105793(2021) [pubmed] |
Keyword List
submitter keyword: glutathionylation, HLH-30, lysosomes, TFEB, TFE3 |
Contact List
Rosa Puertollano |
contact affiliation | Laboratory of Cell Biology, Cell and Developmental Biology Center, National Heart, Lung and Blood Institute, National Institutes of Health, USA |
contact email | puertolr@nhlbi.nih.gov |
lab head | |
Jose Martina |
contact affiliation | Laboratory of Cell Biology, Cell and Developmental Biology Center, National Heart, Lung and Blood Institute, National Institutes of Health |
contact email | jmartina@nhlbi.nih.gov |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
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[ - ]
- PRIDE
- PXD022258
- Label: PRIDE project
- Name: A conserved cysteine-based redox mechanism sustains TFEB/HLH-30 activity under persistent stress