Cited by 162PARP inhibition in cancer therapyCell death mechanisms and regulationDNA Repair Mechanisms

ADP-ribosyl-acceptor hydrolase 3 regulates poly (ADP-ribose) degradation and cell death during oxidative stress

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Mashimo, Masato, Kato, Jiro, Moss, Joel·2013·Proceedings of the National Academy of Sciences

Abstract

Significance: Poly (ADP-ribose) (PAR) participates in initiating parthanatos, cell death mediated by apoptosis-inducing factor (AIF), following genotoxic stress. PAR translocation from the nucleus to cytoplasm is an essential step for AIF-mediated cell death. Here, we report that poly (ADP-ribose) glycohydrolase (PARG) enhances PAR translocation by releasing protein-free PAR fragments from nuclear acceptor proteins. ADP-ribosyl-acceptor hydrolase (ARH) 3 lowers PAR levels in the nucleus and cytoplasm, preventing PAR translocation and then parthanatos. Elucidation of the sequential action of PARG and ARH3 in the PAR-mediated pathway provides a better understanding of mechanisms underlying oxidative stress and may lead to new therapeutic targets.

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  • ADPRHL2 and RNF146 prevent AIF release and consequent RCD by decreasing poly(ADP-ribose) levels and availability.

    “the poly(ADP-ribose)-degrading protein ADP-ribosylhydrolase like 2 (ADPRHL2; also known as ARH3) and the poly(ADP-ribose)-binding protein ring finger protein 146 (RNF146; best known as IDUNA) prevent AIF release and consequent RCD as they decrease poly(ADP-ribose) levels and availability, respectively [662, 668].”

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Authors
Mashimo, M., Kato, J., & Moss, J.
Affiliations
National Institutes of Health (US)
Venue
Proceedings of the National Academy of Sciences
Published
2013-11-04
Volume
110
Issue
47
Pages
18964-18969
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2110712267
Cited by
162
References
43
Citations by year
2026: 4 · 2025: 11 · 2024: 15 · 2023: 15 · 2022: 13 · 2021: 17 · 2020: 18 · 2019: 13 · 2018: 16 · 2017: 8 · 2016: 15 · 2015: 8 · 2014: 9
FWCI
5.72
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institutes of Health
Topics
  • Health Sciences › Medicine › Oncology › PARP inhibition in cancer therapy
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
Keywords
parthanatos, apoptosis-inducing factor, caspase-independent cell death, oxidative stress, hydrogen peroxide, mitochondrial release, DNA cleavage
MeSH terms
Analysis of Variance, Animals, Glycoside Hydrolases, Immunohistochemistry, Poly Adenosine Diphosphate Ribose, Blotting, Western, Cell Death, Oxidative Stress, Immunoprecipitation, Apoptosis Inducing Factor, Mice, Proteolysis, Real-Time Polymerase Chain Reaction

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