ArticleJournal of the American Chemical Society2017
The New Chemical Reporter 6-Alkynyl-6-deoxy-GlcNAc Reveals O-GlcNAc Modification of the Apoptotic Caspases That Can Block the Cleavage/Activation of Caspase-8.
Article in Journal of the American Chemical Society, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed.
- Iterative Bump-and-Hole Engineering Creates a Bioorthogonal Reporter forJournal of the American Chemical Society · 2026Article
- Iterative Bump-and-hole engineering creates a bioorthogonal reporter forbioRxiv : the preprint server for biology · 2026Article
- Targeting panoptosis: a narrative review of its therapeutic potential in kidney disease.BMC nephrology · 2025Review
- Review
- How does caspases regulation play role in cell decisions? apoptosis and beyond.Molecular and cellular biochemistry · 2024Review
- Targeted Protein O-GlcNAcylation Using Bifunctional Small Molecules.Journal of the American Chemical Society · 2024Article
- HSP27 Inhibitory Activity against Caspase-3 Cleavage and Activation by Caspase-9 Is Enhanced by Chaperone O-GlcNAc ModificationACS chemical biology · 2023Article
- Chemical Biology Approaches to Understanding Neuronal O-GlcNAcylation.Israel journal of chemistry · 2023Article
- Article
- Tools for mammalian glycoscience research.Cell · 2022Review
- 4-Deoxy-4-fluoro-GalNAz (4FGalNAz) Is a Metabolic Chemical Reporter of O-GlcNAc Modifications, Highlighting the Notable Substrate Flexibility of O-GlcNAc Transferase.ACS chemical biology · 2022Article
- Advances in chemical probing of proteinChemical Society reviews · 2021Review
- O-GlcNAcylated peptides and proteins for structural and functional studies.Current opinion in structural biology · 2021Review
- Design and Synthesis of Metabolic Chemical Reporters for the Visualization and Identification of Glycoproteins.RSC chemical biology · 2021Article
- Mass Spectrometry for O-GlcNAcylation.Frontiers in chemistry · 2021Review
- O-GlcNAcylation in Chronic Lymphocytic Leukemia and Other Blood Cancers.Frontiers in immunology · 2021Review
- The Metabolic Chemical Reporter AcFrontiers in chemistry · 2021Article
- Metabolic precision labeling enables selective probing of O-linkedProceedings of the National Academy of Sciences of the United States of America · 2020Article
- Tools for functional dissection of site-specific O-GlcNAcylation.RSC chemical biology · 2020Review
- Metabolic Labeling for the Visualization and Identification of Potentially O-GlcNAc-Modified Proteins.Current protocols in chemical biology · 2020Article
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Authors and funding
8 authors.
Funding
Abstract
O-GlcNAc modification (O-GlcNAcylation) is required for survival in mammalian cells. Genetic and biochemical experiments have found that increased modification inhibits apoptosis in tissues and cell culture and that lowering O-GlcNAcylation induces cell death. However, the molecular mechanisms by which O-GlcNAcylation might inhibit apoptosis are still being elucidated. Here, we first synthesize a new metabolic chemical reporter, 6-Alkynyl-6-deoxy-GlcNAc (6AlkGlcNAc), for the identification of O-GlcNAc-modified proteins. Subsequent characterization of 6AlkGlcNAc shows that this probe is selectively incorporated into O-GlcNAcylated proteins over cell-surface glycoproteins. Using this probe, we discover that the apoptotic caspases are O-GlcNAcylated, which we confirmed using other techniques, raising the possibility that the modification affects their biochemistry. We then demonstrate that changes in the global levels of O-GlcNAcylation result in a converse change in the kinetics of caspase-8 activation during apoptosis. Finally, we show that caspase-8 is modified at residues that can block its cleavage/activation. Our results provide the first evidence that the caspases may be directly affected by O-GlcNAcylation as a potential antiapoptotic mechanism.
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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.