Evidence map›Paper›PMID 41499238›Full record

ArticleCell reports2026

PARG regulates the proteasomal degradation of TARG1.

Joséphine Groslambert, Sara C Buch-Larsen, Ivo A Hendriks, Robert Kurzbauer, Jonas D Elsborg, Chatrin Chatrin, Thomas Agnew, Callum Henfrey, Michael Tellier, Evgeniia Prokhorova and 6 more

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In one paragraph

Article in Cell reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

16 authors.

Joséphine GroslambertSir William Dunn School of Pathology, University of Oxford, Oxford, UK.
Sara C Buch-LarsenNovo Nordisk Foundation Center for Protein Research, Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Ivo A HendriksNovo Nordisk Foundation Center for Protein Research, Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Robert KurzbauerResearch Institute of Molecular Pathology, Vienna BioCenter (VBC), Vienna, Austria.
Jonas D ElsborgSir William Dunn School of Pathology, University of Oxford, Oxford, UK; Novo Nordisk Foundation Center for Protein Research, Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Chatrin ChatrinSir William Dunn School of Pathology, University of Oxford, Oxford, UK.
Thomas AgnewSir William Dunn School of Pathology, University of Oxford, Oxford, UK.
Callum HenfreySir William Dunn School of Pathology, University of Oxford, Oxford, UK.
Michael TellierDepartment of Molecular and Cell Biology, University of Leicester, Leicester, UK.
Evgeniia ProkhorovaSir William Dunn School of Pathology, University of Oxford, Oxford, UK.
Song My HoangDepartment of Pharmacology and Chemical Biology, UPMC Hillman Cancer, University of Pittsburgh, Pittsburgh, PA, USA.
Jonathan Barosso-GonzalezDepartment of Pharmacology and Chemical Biology, UPMC Hillman Cancer, University of Pittsburgh, Pittsburgh, PA, USA.
Roderick J O'SullivanDepartment of Pharmacology and Chemical Biology, UPMC Hillman Cancer, University of Pittsburgh, Pittsburgh, PA, USA.
Tim ClausenResearch Institute of Molecular Pathology, Vienna BioCenter (VBC), Vienna, Austria.
Michael L NielsenNovo Nordisk Foundation Center for Protein Research, Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Ivan AhelSir William Dunn School of Pathology, University of Oxford, Oxford, UK. Electronic address: ivan.ahel@path.ox.ac.uk.

Funding

Inhibition of the ALT pathway by interfering with Poly-ADP-Ribose metabolismR01CA207209 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Roderick O'Sullivan · 2016 to 2026
$3.6M
NCI NIH HHS R01 CA207209
6 · The paper itself

Abstract

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 functions and regulatory mechanisms of ADPr hydrolases are still poorly understood. Here, we identify a function of the poly(ADP-ribose) glycohydrolase PARG in regulating protein degradation. Using quantitative proteomics, we show that PARG inhibition depletes protein levels of the mono-ADPr hydrolase TARG1. We demonstrate that this TARG1 depletion is both PAR and proteasome dependent and identify the E3 ubiquitin ligases HUWE1 and TRIP12 as mediators of this process. Our findings establish TARG1 as a substrate of PAR-dependent protein degradation and uncover a PARG-dependent mechanism controlling its stability. This work highlights an interplay between the two ADP-ribosyl hydrolases, with implications for the refinement of PARG-targeted therapeutic strategies.

Indexed as

Glycoside HydrolasesProteasome Endopeptidase ComplexProteolysisADP-RibosylationHEK293 CellsHumansUbiquitin-Protein LigasesGlycoside Hydrolasespoly ADP-ribose glycohydrolaseProteasome Endopeptidase ComplexUbiquitin-Protein LigasesADP-ribosylationCP: molecular biologyDNA damagePARPproteasomal degradationubiquitylation

Identifiers

PMID41499238
PMCPMC13332792

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.