ArticleThe Journal of biological chemistry2016
Glyceraldehyde-3-Phosphate Dehydrogenase (GAPDH) Protein-Protein Interaction Inhibitor Reveals a Non-catalytic Role for GAPDH Oligomerization in Cell Death.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 45 citations in OpenAlex.
- Non-Reducing Proteomics Reveals Disulfide-dependent Proteoform Remodeling Under Oxidative Stress.Molecular & cellular proteomics : MCP · 2026Article
- Proteomics and tracer metabolomics link GAPDH ISGylation to glycolytic control.Genome biology · 2026Article
- Multi-Target Cardioprotective Potential ofBiomarker insights · 2026Article
- Lithium-induced neuroprotection in bipolar disorder: Translational insights into cytoskeletal and proteomic mechanisms.IBRO neuroscience reports · 2025Review
- The tumor suppressor Parkin exerts anticancer effects through regulating mitochondrial GAPDH activity.Oncogene · 2024Article
- Glycolytic enzymes in non-glycolytic web: functional analysis of the key players.Cell biochemistry and biophysics · 2024Review
- GINv2.0: a comprehensive topological network integrating molecular interactions from multiple knowledge bases.NPJ systems biology and applications · 2024Article
- Carbon and energy metabolism for the mixotrophic culture ofFrontiers in microbiology · 2024Article
- NO enhances the adaptability to high-salt environments by regulating osmotic balance, antioxidant defense, and ion homeostasis in eelgrass based on transcriptome and metabolome analysis.Frontiers in plant science · 2024Article
- An Update on Protein Kinases as Therapeutic Targets-Part II: Peptides as Allosteric Protein Kinase C Modulators Targeting Protein-Protein Interactions.International journal of molecular sciences · 2023Review
- Cellular Exposure to Chloroacetanilide Herbicides Induces Distinct Protein Destabilization Profiles.ACS chemical biology · 2023Article
- Biochemical evidence that the whole compartment activity behavior of GAPDH differs between the cytoplasm and nucleus.PloS one · 2023Article
- De Novo Development of Mitochondria-Targeted Molecular Probes Targeting Pink1.International journal of molecular sciences · 2022Article
- Oxidized GAPDH transfers S-glutathionylation to a nuclear protein Sirtuin-1 leading to apoptosis.Free radical biology & medicine · 2021Article
- Article
- Glyceraldehyde-3-phosphate dehydrogenase from Eimeria acervulina modulates the functions of chicken dendritic cells to boost Th1 type immune response and stimulates autologous CD4Veterinary research · 2020Article
- Assessing heterogeneity among single embryos and single blastomeres using open microfluidic design.Science advances · 2020Article
- Identification of Bacterial Protein Interaction Partners Points to New Intracellular Functions ofFrontiers in microbiology · 2020Article
- Neuroprotective effect of grape seed extract on brain ischemia: a proteomic approach.Metabolic brain disease · 2019Article
- A selective inhibitor of mitofusin 1-βIIPKC association improves heart failure outcome in rats.Nature communications · 2019Article
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), an important glycolytic enzyme, has a non-catalytic (thus a non-canonical) role in inducing mitochondrial elimination under oxidative stress. We recently demonstrated that phosphorylation of GAPDH by δ protein kinase C (δPKC) inhibits this GAPDH-dependent mitochondrial elimination. δPKC phosphorylation of GAPDH correlates with increased cell injury following oxidative stress, suggesting that inhibiting GAPDH phosphorylation should decrease cell injury. Using rational design, we identified pseudo-GAPDH (ψGAPDH) peptide, an inhibitor of δPKC-mediated GAPDH phosphorylation that does not inhibit the phosphorylation of other δPKC substrates. Unexpectedly, ψGAPDH decreased mitochondrial elimination and increased cardiac damage in an animal model of heart attack. Either treatment with ψGAPDH or direct phosphorylation of GAPDH by δPKC decreased GAPDH tetramerization, which corresponded to reduced GAPDH glycolytic activity in vitro and ex vivo Taken together, our study identified the potential mechanism by which oxidative stress inhibits the protective GAPDH-mediated elimination of damaged mitochondria. Our study also identified a pharmacological tool, ψGAPDH peptide, with interesting properties. ψGAPDH peptide is an inhibitor of the interaction between δPKC and GAPDH and of the resulting phosphorylation of GAPDH by δPKC. ψGAPDH peptide is also an inhibitor of GAPDH oligomerization and thus an inhibitor of GAPDH glycolytic activity. Finally, we found that ψGAPDH peptide is an inhibitor of the elimination of damaged mitochondria. We discuss how this unique property of increasing cell damage following oxidative stress suggests a potential use for ψGAPDH peptide-based therapy.
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Registered trials
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