ArticleRedox biology2020
Covalent Aurora A regulation by the metabolic integrator coenzyme A.
Article in Redox biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 69 citations in OpenAlex.
- Covalent Modification of Keap1 by the Key Metabolic Cofactor Coenzyme A Under Oxidative and Metabolic Stress.Antioxidants (Basel, Switzerland) · 2026Article
- Levels of Protein CoAlation Regulate Redox Signaling Events of Human Sperm Capacitation.Antioxidants (Basel, Switzerland) · 2026Article
- A dose-dependent switch in translation capacity controls the transcription factor response to HbioRxiv : the preprint server for biology · 2026Article
- Coenzyme A in Brain Biology and Neurodegeneration.Biomedicines · 2025Review
- Coenzyme A protects against ferroptosis via CoAlation of mitochondrial thioredoxin reductase.The Journal of clinical investigation · 2025Article
- Role of Redox-Induced Protein Modifications in Spermatozoa in Health and Disease.Antioxidants (Basel, Switzerland) · 2025Review
- Article
- Immunofluorescent detection of protein CoAlation in mammalian cells under oxidative stress.Biology open · 2024Article
- The significant others of aurora kinase a in cancer: combination is the key.Biomarker research · 2024Review
- Investigating the Regulation of Ribosomal Protein S6 Kinase 1 by CoAlation.International journal of molecular sciences · 2024Article
- Redox Regulation of Brain Selective Kinases BRSK1/2: Implications for Dynamic Control of the Eukaryotic AMPK family through Cys-based mechanisms.bioRxiv : the preprint server for biology · 2024Article
- Comprehensive Profiling and Therapeutic Insights into Differentially Expressed Genes in Hepatocellular Carcinoma.Cancers · 2023Article
- ASPP2 Is Phosphorylated by CDK1 during Mitosis and Required for Pancreatic Cancer Cell Proliferation.Cancers · 2023Article
- Considerations for defining +80 Da mass shifts in mass spectrometry-based proteomics: phosphorylation and beyond.Chemical communications (Cambridge, England) · 2023Review
- A critical evaluation of protein kinase regulation by activation loop autophosphorylation.eLife · 2023Article
- Emerging roles of Aurora-A kinase in cancer therapy resistance.Acta pharmaceutica Sinica. B · 2023Review
- A mitotic NADPH upsurge promotes chromosome segregation and tumour progression in aneuploid cancer cells.Nature metabolism · 2023Article
- A Unique Mode of Coenzyme A Binding to the Nucleotide Binding Pocket of Human Metastasis Suppressor NME1.International journal of molecular sciences · 2023Article
- Structural basis for CEP192-mediated regulation of centrosomal AURKA.Science advances · 2023Article
- Article
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Authors and funding
24 authors at 7 institutions in 3 countries.
Funding
Abstract
Aurora A kinase is a master mitotic regulator whose functions are controlled by several regulatory interactions and post-translational modifications. It is frequently dysregulated in cancer, making Aurora A inhibition a very attractive antitumor target. However, recently uncovered links between Aurora A, cellular metabolism and redox regulation are not well understood. In this study, we report a novel mechanism of Aurora A regulation in the cellular response to oxidative stress through CoAlation. A combination of biochemical, biophysical, crystallographic and cell biology approaches revealed a new and, to our knowledge, unique mode of Aurora A inhibition by CoA, involving selective binding of the ADP moiety of CoA to the ATP binding pocket and covalent modification of Cys290 in the activation loop by the thiol group of the pantetheine tail. We provide evidence that covalent CoA modification (CoAlation) of Aurora A is specific, and that it can be induced by oxidative stress in human cells. Oxidising agents, such as diamide, hydrogen peroxide and menadione were found to induce Thr 288 phosphorylation and DTT-dependent dimerization of Aurora A. Moreover, microinjection of CoA into fertilized mouse embryos disrupts bipolar spindle formation and the alignment of chromosomes, consistent with Aurora A inhibition. Altogether, our data reveal CoA as a new, rather selective, inhibitor of Aurora A, which locks this kinase in an inactive state via a "dual anchor" mechanism of inhibition that might also operate in cellular response to oxidative stress. Finally and most importantly, we believe that these novel findings provide a new rationale for developing effective and irreversible inhibitors of Aurora A, and perhaps other protein kinases containing appropriately conserved Cys residues.
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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.