PXD053308-1

PXD053308 is an original dataset announced via ProteomeXchange.

Title	Targeted dephosphorylation of TFEB promotes its nuclear translocation
Description	Reversible phosphorylation of the transcription factor EB (TFEB) coordinates cellular responses to metabolic and other stresses. During nutrient replete and stressor-free conditions, phosphorylated TFEB is primarily localised to the cytoplasm. Stressor-mediated reduction of TFEB phosphorylation promotes its nuclear translocation and context-dependent transcriptional activity. In this study, we explored targeted dephosphorylation of TFEB as an approach to activate TFEB in the absence of nutrient deprivation or other cellular stress. Through an induction of proximity between TFEB and several phosphatases using the AdPhosphatase system, we demonstrate targeted dephosphorylation of TFEB in cells. Furthermore, by developing a heterobifunctional molecule BDPIC (bromoTAG-dTAG proximity-inducing chimera), we demonstrate targeted dephosphorylation of TFEB-dTAG through induced proximity to bromoTAG-PPP2CA. Targeted dephosphorylation of TFEB-dTAG by bromoTAG-PPP2CA with BDPIC at the endogenous levels is sufficient to induce nuclear translocation and some transcriptional activity of TFEB.
HostingRepository	PRIDE
AnnounceDate	2024-08-09
AnnouncementXML	Submission_2024-08-09_03:21:03.228.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Gopal Sapkota
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-06-22 21:06:42	ID requested
⏵ 1	2024-08-09 03:21:04	announced
2	2024-10-22 06:53:40	announced	2024-10-22: Updated project metadata.

10.1016/j.isci.2024.110432;

Zhao JF, Shpiro N, Sathe G, Brewer A, Macartney TJ, Wood NT, Negoita F, Sakamoto K, Sapkota GP, Targeted dephosphorylation of TFEB promotes its nuclear translocation. iScience, 27(8):110432(2024) [pubmed]

submitter keyword: BDPIC, PPP2CA,TFEB, AdPhosphatase, PHOSTAC

Gopal Sapkota
contact affiliation	Dr Prof .Gopal Sapkota, MRC PPU, School of Life Sciences University of Dundee (lab head)
contact email	g.sapkota@dundee.ac.uk
lab head
Gopal Sapkota
contact affiliation	University of Dundee
contact email	g.sapkota@dundee.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/2024/08/PXD053308

PRIDE project URI

• PRIDE
  1. PXD053308
     1. Label: PRIDE project
     2. Name: Targeted dephosphorylation of TFEB promotes its nuclear translocation