ArticleProceedings of the National Academy of Sciences of the United States of America2006
Direct phosphorylation and regulation of poly(ADP-ribose) polymerase-1 by extracellular signal-regulated kinases 1/2.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 121 papers, 1 of them a synthesis that pooled it.
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Who cites it
121 citing papers in PubMed, 1 synthesis or guideline pooled it, 208 citations in OpenAlex.
- Comprehensive analysis of regulated cell death pathways: intrinsic disorder, protein-protein interactions, and cross-pathway communication.Apoptosis : an international journal on programmed cell death · 2025Pooled it
- Associations between polymorphisms in DNA repair genes and glioblastoma.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2009Trial
- Effects of a cancer-associated mutation and multiple serine phosphorylation on poly(ADP-ribose) polymerase 2.Biophysical journal · 2026Article
- PARylation-mediated post-transcriptional modifications in cancer immunity and immunotherapy.Frontiers in immunology · 2025Review
- Leveraging PARP-1/2 to Target Distant Metastasis.International journal of molecular sciences · 2024Review
- The TAS1R2 G-protein-coupled receptor is an ambient glucose sensor in skeletal muscle that regulates NAD homeostasis and mitochondrial capacity.Nature communications · 2024Article
- 1,25-Dihydroxyvitamin DInternational journal of molecular sciences · 2024Article
- PARP14 Contributes to the Development of the Tumor-Associated Macrophage Phenotype.International journal of molecular sciences · 2024Article
- The interplay of mitophagy, autophagy, and apoptosis in cisplatin-induced kidney injury: involvement of ERK signaling pathway.Cell death discovery · 2024Article
- The Ser/Thr protein kinase FonKin4-poly(ADP-ribose) polymerase FonPARP1 phosphorylation cascade is required for the pathogenicity of watermelon fusarium wilt fungusFrontiers in microbiology · 2024Article
- Vesicular translocation of PARP-1 to cytoplasm causes ADP-ribosylation and disassembly of vimentin filaments during microglia activation induced by LPS.Frontiers in cellular neuroscience · 2024Article
- Metformin pretreatment ameliorates busulfan-induced liver endothelial toxicity during haematopoietic stem cell transplantation.PloS one · 2023Article
- Advances in the study of the molecular biological mechanisms of radiation-induced brain injury.American journal of cancer research · 2023Review
- DNA Damage Regulates the Functions of the RNA Binding Protein Sam68 through ATM-Dependent Phosphorylation.Cancers · 2022Article
- Poly (ADP-ribose) polymerase: An Overview of Mechanistic Approaches and Therapeutic Opportunities in the Management of Stroke.Neurochemical research · 2022Review
- β-Hydroxybutyrate Alleviates Low Glucose-Induced Apoptosis via Modulation of ROS-Mediated p38 MAPK Signaling.Journal of molecular neuroscience : MN · 2022Article
- Therapeutic Potentials of Poly (ADP-Ribose) Polymerase 1 (PARP1) Inhibition in Multiple Sclerosis and Animal Models: Concept Revisiting.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Review
- Bad Smells and Broken DNA: A Tale of Sulfur-Nucleic Acid Cooperation.Antioxidants (Basel, Switzerland) · 2021Review
- Interplay between ADP-ribosyltransferases and essential cell signaling pathways controls cellular responses.Cell discovery · 2021Review
- The regulatory landscape of the human HPF1- and ARH3-dependent ADP-ribosylome.Nature communications · 2021Article
61 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
Sustained activation of poly(ADP-ribose) polymerase-1 (PARP-1) and extracellular signal-regulated kinases 1/2 (ERK1/2) both promote neuronal death. Here we identify a direct link between these two cell death pathways. In a rat model of hypoglycemic brain injury, neuronal PARP-1 activation and subsequent neuronal death were blocked by the ERK1/2 inhibitor 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one (PD98059). In neuron cultures, PARP-1-mediated neuronal death induced by N-methyl-d-aspartate, peroxynitrite, or DNA alkylation was similarly blocked by ERK1/2 pathway inhibitors. These inhibitors also blocked PARP-1 activation and PARP-1-mediated death in astrocytes. siRNA down-regulation of ERK2 expression in astrocytes also blocked PARP-1 activation and cell death. Direct effects of ERK1/2 on PARP-1 were evaluated by using isolated recombinant enzymes. The activity of recombinant human PARP-1 was reduced by incubation with alkaline phosphatase and restored by incubation with active ERK1 or ERK2. Putative ERK1/2 phosphorylation sites on PARP-1 were identified by mass spectrometry. Using site-directed mutagenesis, these sites were replaced with alanine (S372A and T373A) to block phosphorylation, or with glutamate (S372E and T373E) to mimic constitutive phosphorylation. Transfection of PARP-1 deficient mouse embryonic fibroblasts with the mutant PARP-1 species showed that the S372A and T373A mutations impaired PARP-1 activation, whereas the S372E and T373E mutations increased PARP-1 activity and eliminated the effect of ERK1/2 inhibitors on PARP-1 activation. These results suggest that PARP1 phosphorylation by ERK1/2 is required for maximal PARP-1 activation after DNA damage.
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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.