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 PARG regulates the proteasomal degradation of TARG1

GSE310746 Homo sapiens Expression profiling by high throughput sequencing 6 samples Submitted 2025/11/25 Platform GPL24676
Summary
ADP-ribosylation 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 previously uncharacterized 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 a new dimension of interplay between the two ADP-ribosyl hydrolases, with implications for the refinement of PARG-targeted therapeutic strategies.
Published in
PARG regulates the proteasomal degradation of TARG1
Groslambert J, Buch-Larsen SC, Hendriks IA et al. · Cell reports 2026 · PMID 41499238 · doi:10.1016/j.celrep.2025.116789
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Also filed as BioProject PRJNA1367021 and SRA study SRP647290. Searching any of these in the dataset finder brings you back here.

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