ArticleFree radical biology & medicine2007
Molecular mechanism of human Nrf2 activation and degradation: role of sequential phosphorylation by protein kinase CK2.
Article in Free radical biology & medicine, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers.
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Who cites it
85 citing papers in PubMed, 210 citations in OpenAlex.
- The AMPK/NRF2/FOXO Axis in CKD-Molecular and Clinical Perspectives.Antioxidants (Basel, Switzerland) · 2026Review
- Multi-omic analysis of human PHACTR1 signaling networks.Communications biology · 2026Article
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- Protective Roles of Zinc and Selenium Against Oxidative Stress in Brain Endothelial Cells Under Shear Stress.Antioxidants (Basel, Switzerland) · 2025Article
- Considerations for antibody-based detection of NRF2 in human cells.Redox biology · 2025Article
- Mechanistic insights into Nrf2-driven pathogenesis and therapeutic targeting in spinal cord injury.Frontiers in immunology · 2025Review
- Role of Oxidative Stress and Inflammation in Doxorubicin-Induced Cardiotoxicity: A Brief Account.International journal of molecular sciences · 2024Review
- Isoliquiritigenin as a modulator of the Nrf2 signaling pathway: potential therapeutic implications.Frontiers in pharmacology · 2024Review
- The master antioxidant defense is activated during EBV latent infection.Journal of virology · 2023Article
- Formulation and Investigation of CK2 Inhibitor-Loaded Alginate Microbeads with Different Excipients.Pharmaceutics · 2023Article
- How to deal with frenemy NRF2: Targeting NRF2 for chemoprevention and cancer therapy.Journal of food and drug analysis · 2023Review
- Aging, NRF2, and TAU: A Perfect Match for Neurodegeneration?Antioxidants (Basel, Switzerland) · 2023Review
- Nrf2: a dark horse in doxorubicin-induced cardiotoxicity.Cell death discovery · 2023Review
- Interplay of Oxidative Stress, Inflammation, and Autophagy in RAW 264.7 Murine Macrophage Cell Line Challenged with Si/SiOMaterials (Basel, Switzerland) · 2023Article
- The Nrf2 Pathway in Depressive Disorders: A Systematic Review of Animal and Human Studies.Antioxidants (Basel, Switzerland) · 2023Review
- Protective Impact of Edaravone Against ZnO NPs-induced Oxidative Stress in the Human Neuroblastoma SH-SY5Y Cell Line.Cellular and molecular neurobiology · 2022Article
- Recent Advances in Understanding Nrf2 Agonism and Its Potential Clinical Application to Metabolic and Inflammatory Diseases.International journal of molecular sciences · 2022Review
- Article
- Extracellular Calcium Receptor as a Target for Glutathione and Its Derivatives.International journal of molecular sciences · 2022Review
- Role of Nrf2 Signaling Cascade in Breast Cancer: Strategies and Treatment.Frontiers in pharmacology · 2022Review
25 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 6 institutions in 2 countries.
Funding
Abstract
Nrf2 is a key transcription factor in the cellular response to oxidative stress. In this study we identify two phosphorylated forms of endogenous human Nrf2 after chemically induced oxidative stress and provide evidence that protein kinase CK2-mediated sequential phosphorylation plays potential roles in Nrf2 activation and degradation. Human Nrf2 has a predicted molecular mass of 66 kDa. However, immunoblots showed that two bands at 98 and 118 kDa, which are identified as phosphorylated forms, are increased in response to Nrf2 inducers. In addition, human Nrf2 was found to be a substrate for CK2 which mediated two steps of phosphorylation, resulting in two forms of Nrf2 migrating with differing M(r) at 98 kDa (Nrf2-98) and 118 kDa (Nrf2-118). Our results support a role in which calmodulin binding regulates CK2 activity, in that cold (25 degrees C) Ca(2+)-free media (cold/Ca(2+)-free) decreased both cellular calcium levels and CK2-calmodulin binding and induced Nrf2-118 formation, the latter of which was prevented by CK2-specific inhibitors. Gel shift assays showed that the Nrf2-118 generated under cold/Ca(2+)-free conditions does not bind to the antioxidant response element, indicating that Nrf2-98 has transcriptional activity. In contrast, Nrf2-118 is more susceptible to degradation. These results provide evidence for phosphorylation by CK2 as a critical controlling factor in Nrf2-mediated cellular antioxidant response.
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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.