PXD055937

PXD055937 is an original dataset announced via ProteomeXchange.

Title	USP7 protects TFEB from proteasome-mediated degradation
Description	The transcription factor EB (TFEB) is a master regulator of lysosomal biogenesis and autophagy. We identify a distinct nuclear interactome of TFEB, with USP7 emerging as a key post-translational modulator of TFEB. Genetic depletion and inhibition of USP7 reveal its critical role in preserving TFEB stability within both nuclear and cytoplasmic compartments. Specifically, USP7 is identified as the deubiquitinase responsible for removing the K48-linked polyubiquitination signal from TFEB at lysine residues K116, K264, and K274, thereby preventing its proteasomal degradation. Functional assays demonstrate the involvement of USP7 in preserving TFEB-mediated transcriptional responses to nutrient deprivation, while also modulating autophagy flux and lysosome biogenesis. As USP7 is a deubiquitinase that protects TFEB from proteasomal degradation, these findings provide the foundation for therapeutic targeting of the USP7-TFEB axis in conditions characterized by TFEB dysregulation and metabolic abnormalities, particularly in certain cancers.
HostingRepository	PRIDE
AnnounceDate	2024-09-17
AnnouncementXML	Submission_2024-09-17_08:05:18.535.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Robin Antrobus
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2024-09-17 07:39:02	ID requested
⏵ 1	2024-09-17 08:05:18	announced

Dataset with its publication pending

submitter keyword: lysosomal biogenesis, IP-mass spectrometry,Autophagy

David C. Rubinsztein1
contact affiliation	Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, UK.
contact email	dcr1000@cam.ac.uk
lab head
Robin Antrobus
contact affiliation	CIMR medicine
contact email	pra29@cam.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD055937
     1. Label: PRIDE project
     2. Name: USP7 protects TFEB from proteasome-mediated degradation