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PXD022258

PXD022258 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleA conserved cysteine-based redox mechanism sustains TFEB/HLH-30 activity under persistent stress
DescriptionMammalian 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.
HostingRepositoryPRIDE
AnnounceDate2021-01-22
AnnouncementXMLSubmission_2021-01-21_23:48:12.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterJose Martina
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListphosphorylated residue; monohydroxylated residue; L-cysteine glutathione disulfide
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-10-30 02:26:44ID requested
12021-01-21 23:48:13announced
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 affiliationLaboratory of Cell Biology, Cell and Developmental Biology Center, National Heart, Lung and Blood Institute, National Institutes of Health, USA
contact emailpuertolr@nhlbi.nih.gov
lab head
Jose Martina
contact affiliationLaboratory of Cell Biology, Cell and Developmental Biology Center, National Heart, Lung and Blood Institute, National Institutes of Health
contact emailjmartina@nhlbi.nih.gov
dataset submitter
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Dataset FTP location
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