ArticleThe Journal of biological chemistry2013
Trafficking of the transcription factor Nrf2 to promyelocytic leukemia-nuclear bodies: implications for degradation of NRF2 in the nucleus.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 75 citations in OpenAlex.
- Interplay between NRF2 post-translational modifications and protein-protein interactions: Perspectives from emerging structural and functional evidence.Archives of biochemistry and biophysics · 2026Review
- SENP6-Mediated deSUMOylation of Nrf2 Exacerbates Neuronal Oxidative Stress Following Cerebral Ischemia and Reperfusion Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Article
- How to deal with frenemy NRF2: Targeting NRF2 for chemoprevention and cancer therapy.Journal of food and drug analysis · 2023Review
- The PML hub: An emerging actor of leukemia therapies.The Journal of experimental medicine · 2023Article
- SARS-CoV-2 Inhibits NRF2-Mediated Antioxidant Responses in Airway Epithelial Cells and in the Lung of a Murine Model of Infection.Microbiology spectrum · 2023Article
- The untapped potential of targeting NRF2 in neurodegenerative disease.Frontiers in aging · 2023Article
- NRF2 and Diabetes: The Good, the Bad, and the Complex.Diabetes · 2022Review
- The Antioxidant Transcription Factor Nrf2 in Cardiac Ischemia-Reperfusion Injury.International journal of molecular sciences · 2021Review
- SUMO-Targeted Ubiquitin Ligases and Their Functions in Maintaining Genome Stability.International journal of molecular sciences · 2021Review
- Mechanistic role of antioxidants in rescuing delayed gastric emptying in high fat diet induced diabetic female mice.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2021Article
- NRF2 activation induced by PML-RARα promotes microRNA 125b-1 expression and confers resistance to chemotherapy in acute promyelocytic leukemia.Clinical and translational medicine · 2021Article
- SUMO-Modification of Human Nrf2 at KCellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology · 2021Article
- An Overview of the Posttranslational Modifications and Related Molecular Mechanisms in Diabetic Nephropathy.Frontiers in cell and developmental biology · 2021Review
- Article
- SUMO promotes longevity and maintains mitochondrial homeostasis during ageing in Caenorhabditis elegans.Scientific reports · 2020Article
- Old dog, new trick: Trivalent arsenic as an immunomodulatory drug.British journal of pharmacology · 2020Review
- Oxidative contribution of air pollution to extrinsic skin ageing.Free radical biology & medicine · 2020Review
- lncRNA SLC7A11-AS1 Promotes Chemoresistance by Blocking SCFMolecular therapy. Nucleic acids · 2020Article
- Mild Oxidative Stress Reduces NRF2 SUMOylation to PromoteOxidative medicine and cellular longevity · 2020Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Ubiquitylation of Nrf2 by the Keap1-Cullin3/RING box1 (Cul3-Rbx1) E3 ubiquitin ligase complex targets Nrf2 for proteasomal degradation in the cytoplasm and is an extensively studied mechanism for regulating the cellular level of Nrf2. Although mechanistic details are lacking, reports abound that Nrf2 can also be degraded in the nucleus. Here, we demonstrate that Nrf2 is a target for sumoylation by both SUMO-1 and SUMO-2. HepG2 cells treated with As2O3, which enhances attachment of SUMO-2/3 to target proteins, increased SUMO-2/3-modification (polysumoylation) of Nrf2. We show that Nrf2 traffics, in part, to promyelocytic leukemia-nuclear bodies (PML-NBs). Cell fractions harboring key components of PML-NBs did not contain biologically active Keap1 but contained modified Nrf2 as well as RING finger protein 4 (RNF4), a poly-SUMO-specific E3 ubiquitin ligase. Overexpression of wild-type RNF4, but not the catalytically inactive mutant, decreased the steady-state levels of Nrf2, measured in the PML-NB-enriched cell fraction. The proteasome inhibitor MG-132 interfered with this decrease, resulting in elevated levels of polysumoylated Nrf2 that was also ubiquitylated. Wild-type RNF4 accelerated the half-life (t½) of Nrf2, measured in PML-NB-enriched cell fractions. These results suggest that RNF4 mediates polyubiquitylation of polysumoylated Nrf2, leading to its subsequent degradation in PML-NBs. Overall, this work identifies Nrf2 as a target for sumoylation and provides a novel mechanism for its degradation in the nucleus, independent of Keap1.
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Registered trials
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