PXD065407

PXD065407 is an original dataset announced via ProteomeXchange.

Title	PARG regulates the proteosomal degradation of TARG1
Description	ADP-ribosylation (ADPr) is a reversible modification of macromolecules critical for the regulation of genome stability, stress responses, and proteostasis. While the roles of ADPr transferases such as PARP1/2 and TNKS1/2 are well established, the cellular functions and regulatory mechanisms of ADPr hydrolases are still poorly understood. Here, we identify a previously uncharacterized function of the poly(ADP-ribose) glycohydrolase PARG in maintaining protein stability. Using quantitative proteomics, we show that PARG inhibition perturbs proteome homeostasis and leads to the depletion of the mono-ADPr hydrolase TARG1 at the protein—but not transcript—level. We demonstrate that this loss results from enhanced proteasomal degradation and reveal that TARG1 downregulation is PAR- and proteasome-dependent, with the E3 ubiquitin ligase HUWE1 identified as a central mediator of this process. Our findings establish TARG1 as a physiological substrate of PAR-dependent protein degradation and uncover a PARG-dependent mechanism for regulating TARG1 stability. This work highlights a new dimension of interplay between the two ADP-ribosyl hydrolases, with direct implications for the design and refinement of PARG-targeted therapeutic strategies.
HostingRepository	PRIDE
AnnounceDate	2026-01-03
AnnouncementXML	Submission_2026-01-03_00:14:54.934.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jonas D. Elsborg
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-06-24 10:30:56	ID requested
⏵ 1	2026-01-03 00:14:55	announced

Dataset with its publication pending

submitter keyword: PARP, ubiquitination,Proteome, ADP-ribosylation, proteasomal degradation, DNA damage

Michael L. Nielsen
contact affiliation	Novo Nordisk Foundation Center for Protein Research, Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
contact email	michael.nielsen@cpr.ku.dk
lab head
Jonas D. Elsborg
contact affiliation	NNF Center for Protein Research
contact email	jonas.elsborg@cpr.ku.dk
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/2026/01/PXD065407

PRIDE project URI

• PRIDE
  1. PXD065407
     1. Label: PRIDE project
     2. Name: PARG regulates the proteosomal degradation of TARG1