PXD065270

PXD065270 is an original dataset announced via ProteomeXchange.

Title	TFEB Coordinates Autophagosome Biogenesis and Ribophagy during starvation via SQSTM1
Description	(Macro)autophagy is a cellular degradation pathway that delivers substrates to lysosomes via autophag(Macro)autophagy is a cellular degradation pathway that delivers substrates to lysosomes via autophagosomes. Among physiological stimuli, nutrient starvation is the most potent inducer of autophagy. However, the logic behind the selection of the autophagy substrates during starvation is unclear. During starvation, the transcription factor EB (TFEB) becomes activated and promotes the expression of numerous autophagy-related genes. In this study, we demonstrate that TFEB enhances autophagosome biogenesis by driving the formation of p62/SQSTM1 bodies. Within these structures, we identified ubiquitinated ribosomal proteins as key substrates. We found that the E3 ubiquitin ligase ZNF598, a newly identified TFEB target gene, is upregulated during starvation and promotes the ubiquitination of ribosomal proteins, facilitating their sequestration into SQSTM1 bodies. These findings reveal a transcriptionally coordinated mechanism through which TFEB regulates both ubiquitination and autophagy receptors to direct selective cargo clearance during starvation-induced autophagy.osomes. Among physiological stimuli, nutrient starvation is the most potent inducer of autophagy. However, the logic behind the selection of the autophagy substrates during starvation is unclear. During starvation, the transcription factor EB (TFEB) becomes activated and promotes the expression of numerous autophagy-related genes. In this study, we demonstrate that TFEB enhances autophagosome biogenesis by driving the formation of p62/SQSTM1 bodies. Within these structures, we identified ubiquitinated ribosomal proteins as key substrates. We found that the E3 ubiquitin ligase ZNF598, a newly identified TFEB target gene, is upregulated during starvation and promotes the ubiquitination of ribosomal proteins, facilitating their sequestration into SQSTM1 bodies. These findings reveal a transcriptionally coordinated mechanism through which TFEB regulates both ubiquitination and autophagy receptors to direct selective cargo clearance during starvation-induced autophagy.
HostingRepository	PRIDE
AnnounceDate	2025-11-18
AnnouncementXML	Submission_2025-11-18_08:43:29.861.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Maria Iavazzo
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2025-06-20 09:12:39	ID requested
⏵ 1	2025-11-18 08:43:30	announced

10.1126/SCIADV.AEA9302;

submitter keyword: None

Maria Iavazzo
contact affiliation	TIGEM
contact email	m.iavazzo@tigem.it
lab head
Maria Iavazzo
contact affiliation	Telethon Institute of Genetics and Medicine, TIGEM
contact email	m.iavazzo@tigem.it
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/2025/11/PXD065270

PRIDE project URI

• PRIDE
  1. PXD065270
     1. Label: PRIDE project
     2. Name: TFEB Coordinates Autophagosome Biogenesis and Ribophagy during starvation via SQSTM1