PXD009677-2

PXD009677 is an original dataset announced via ProteomeXchange.

Title	A TFEB nuclear export signal integrates amino acid supply and glucose availability
Description	How cells coordinate the response to fluctuating carbon and nitrogen availability required to maintain effective homeostasis is a key issue. Amino acid limitation that inactivates mTORC1 promotes de-phosphorylation and nuclear translocation of Transcription Factor EB (TFEB), a key transcriptional regulator of lysosome biogenesis and autophagy that is deregulated in cancer and neurodegeneration. Beyond its cytoplasmic sequestration, how TFEB phosphorylation regulates its nuclear-cytoplasmic shuttling, and whether TFEB can coordinate amino acid supply with glucose availability is poorly understood. Here we show that TFEB phosphorylation on S142 primes for GSK3 phosphorylation on S138, and that phosphorylation of both sites but not either alone activates a previously unrecognised nuclear export signal (NES). Importantly, GSK3 is inactivated by AKT in response to mTORC2 signalling triggered by glucose limitation. Remarkably therefore, the TFEB NES integrates carbon (glucose) and nitrogen (amino acid) availability by controlling TFEB flux through a nuclear import-export cycle.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:45:02.236.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Georgina Berridge
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; monohydroxylated residue; deamidated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2018-05-04 05:34:44	ID requested
1	2018-10-18 08:10:59	announced
⏵ 2	2024-10-22 04:45:03	announced	2024-10-22: Updated project metadata.

10.1038/s41467-018-04849-7;

Li L, Friedrichsen HJ, Andrews S, Picaud S, Volpon L, Ngeow K, Berridge G, Fischer R, Borden KLB, Filippakopoulos P, Goding CR, A TFEB nuclear export signal integrates amino acid supply and glucose availability. Nat Commun, 9(1):2685(2018) [pubmed]

curator keyword: Biological

submitter keyword: Glucose Lysosome biogenesis Running header: TFEB nuclear export, GSK3,TFEB, Nuclear Export Signal, mTOR

Roman Fischer
contact affiliation	Target discovery Institute
contact email	roman.fischer@ndm.ox.ac.uk
lab head
Georgina Berridge
contact affiliation	University of Oxford
contact email	georgina.berridge@ndm.ox.ac.uk
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/2018/10/PXD009677

PRIDE project URI

• PRIDE
  1. PXD009677
     1. Label: PRIDE project
     2. Name: A TFEB nuclear export signal integrates amino acid supply and glucose availability