ArticleBiochemistry2010
Identification of a regulatory segment of poly(ADP-ribose) glycohydrolase.
Article in Biochemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 28 citations in OpenAlex.
- ADP-ribose hydrolases: biological functions and potential therapeutic targets.Expert reviews in molecular medicine · 2024Review
- PARG Protein Regulation Roles inInternational journal of molecular sciences · 2024Article
- Poly(ADP-ribosyl)ating pathway regulates development from stem cell niche to longevity control.Life science alliance · 2022Article
- Inhibition of the NAD salvage pathway in schistosomes impairs metabolism, reproduction, and parasite survival.PLoS pathogens · 2020Article
- Therapeutic Strategies and Biomarkers to Modulate PARP Activity for Targeted Cancer Therapy.Cancers · 2020Review
- PARG regulates the proliferation and differentiation of DCs and T cells via PARP/NF‑κB in tumour metastases of colon carcinoma.Oncology reports · 2019Article
- Emerging roles of eraser enzymes in the dynamic control of protein ADP-ribosylation.Nature communications · 2019Review
- Poly(ADP-Ribose) Polymerases in Host-Pathogen Interactions, Inflammation, and Immunity.Microbiology and molecular biology reviews : MMBR · 2019Review
- CD38 promotes pristane-induced chronic inflammation and increases susceptibility to experimental lupus by an apoptosis-driven and TRPM2-dependent mechanism.Scientific reports · 2018Article
- Crystallographic and biochemical analysis of the mouse poly(ADP-ribose) glycohydrolase.PloS one · 2014Article
- Structural biology of the writers, readers, and erasers in mono- and poly(ADP-ribose) mediated signaling.Molecular aspects of medicine · 2013Review
- Host cell poly(ADP-ribose) glycohydrolase is crucial for Trypanosoma cruzi infection cycle.PloS one · 2013Article
- Molecular Insights into Poly(ADP-ribose) Recognition and Processing.Biomolecules · 2012Article
- Structure and mechanism of a canonical poly(ADP-ribose) glycohydrolase.Nature communications · 2012Article
- Structure of mammalian poly(ADP-ribose) glycohydrolase reveals a flexible tyrosine clasp as a substrate-binding element.Nature structural & molecular biology · 2012Article
- ADP-ribosylhydrolase 3 (ARH3), not poly(ADP-ribose) glycohydrolase (PARG) isoforms, is responsible for degradation of mitochondrial matrix-associated poly(ADP-ribose).The Journal of biological chemistry · 2012Article
- Article
- Discovery and structure-activity relationships of modified salicylanilides as cell permeable inhibitors of poly(ADP-ribose) glycohydrolase (PARG).Journal of medicinal chemistry · 2011Article
- PARG is recruited to DNA damage sites through poly(ADP-ribose)- and PCNA-dependent mechanisms.Nucleic acids research · 2011Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Coordinate regulation of PARP-1 and -2 and PARG is required for cellular responses to genotoxic stress. While PARP-1 and -2 are regulated by DNA breaks and covalent modifications, mechanisms of PARG regulation are poorly understood. We report here discovery of a PARG regulatory segment far removed linearly from residues involved in catalysis. Expression and analysis of human PARG segments identified a minimal catalytically active C-terminal PARG (hPARG59) containing a 16-residue N-terminal mitochondrial targeting sequence (MTS). Deletion analysis and site-directed mutagenesis revealed that the MTS, specifically hydrophobic residues L473 and L474, was required for PARG activity. This region of PARG was termed the "regulatory segment/MTS" (REG/MTS). The overall alpha-helical composition of hPARG59, determined by circular dichroism (CD), was unaffected by mutation of the REG/MTS leucine residues, suggesting that activity loss was not due to incorrect protein folding. REG/MTS was predicted to be in a loop conformation because the CD spectra of mutant Delta1-16 lacking the REG/MTS showed a higher alpha-helical content than hPARG59, indicating a secondary structure other than alpha-helix for this segment. Deletion of the REG/MTS from full-length hPARG111 also resulted in a complete loss of activity, indicating that all PARG isoforms are subject to regulation at this site. The presence of the REG/MTS raises the possibility that PARG activity is regulated by interactions of PARP-1 and -2 and other proteins at this site, raises interesting questions concerning mitochondrial PARG because MTS residues are often removed after transport, and offers a potentially novel site for drug targeting of PARG.
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Registered trials
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.