PXD022258

PXD022258 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2020-10-30 02:26:44	ID requested
⏵ 1	2021-01-21 23:48:13	announced

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]

submitter keyword: glutathionylation, HLH-30, lysosomes, TFEB, TFE3

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

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/01/PXD022258

PRIDE project URI

• PRIDE
  1. PXD022258
     1. Label: PRIDE project
     2. Name: A conserved cysteine-based redox mechanism sustains TFEB/HLH-30 activity under persistent stress