ArticleMolecular and cellular biology2011
KPNA6 (Importin {alpha}7)-mediated nuclear import of Keap1 represses the Nrf2-dependent antioxidant response.
Article in Molecular and cellular biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 91 citations in OpenAlex.
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- Integrated Analysis of ATAC-Seq and RNA-Seq Reveals the Signal Transduction Regulation of the Molting Cycle in the Muscle of Chinese Mitten Crab (Biomolecules · 2026Article
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- Plant food-derived antioxidant nutrients in neuroprotection against chemotherapy-induced neurotoxicity: from molecular mechanisms to clinical applications.Frontiers in nutrition · 2025Review
- Interplay of Cellular Nrf2/NF-κB Signalling after Plasma Stimulation of Malignant vs. Non-Malignant Dermal Cells.International journal of molecular sciences · 2024Article
- Interaction with B-type lamin reveals the function of Drosophila Keap1 xenobiotic response factor in nuclear architecture.Molecular biology reports · 2024Article
- MicroRNAs in the Pathogenesis of Preeclampsia-A Case-Control In Silico Analysis.Current issues in molecular biology · 2024Article
- Comparative genomic diversity analysis of copy number variations (CNV) in indicine and taurine cattle thriving in Europe and Indian subcontinent.Animal biotechnology · 2023Article
- Roles of Non-Coding RNA in Alzheimer's Disease Pathophysiology.International journal of molecular sciences · 2023Review
- Nrf2 and Oxidative Stress: A General Overview of Mechanisms and Implications in Human Disease.Antioxidants (Basel, Switzerland) · 2022Review
- Overview of the Mechanisms of Oxidative Stress: Impact in Inflammation of the Airway Diseases.Antioxidants (Basel, Switzerland) · 2022Review
- Nrf2/Keap1/ARE signaling: Towards specific regulation.Life sciences · 2022Review
- Divergent Regulation of Decidual Oxidative-Stress Response by NRF2 and KEAP1 in Preeclampsia with and without Fetal Growth Restriction.International journal of molecular sciences · 2022Article
- The Antimalaria Drug Artesunate Inhibits Porcine Reproductive and Respiratory Syndrome Virus Replication by Activating AMPK and Nrf2/HO-1 Signaling Pathways.Journal of virology · 2022Article
- Oxidative Stress-Induced Misfolding and Inclusion Formation of Nrf2 and Keap1.Antioxidants (Basel, Switzerland) · 2022Article
- Drosophila Keap1 xenobiotic response factor regulates developmental transcription through binding to chromatin.Developmental biology · 2022Article
- Impaired antioxidant KEAP1-NRF2 system in amyotrophic lateral sclerosis: NRF2 activation as a potential therapeutic strategy.Molecular neurodegeneration · 2021Review
- Effects of acute iron overload on Nrf2-related glutathione metabolism in rat brain.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2021Article
- Oxidative Stress in Cancer Cell Metabolism.Antioxidants (Basel, Switzerland) · 2021Review
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The transcription factor Nrf2 has emerged as a master regulator of cellular redox homeostasis. As an adaptive response to oxidative stress, Nrf2 activates the transcription of a battery of genes encoding antioxidants, detoxification enzymes, and xenobiotic transporters by binding the cis-antioxidant response element in the promoter regions of genes. The magnitude and duration of inducible Nrf2 signaling is delicately controlled at multiple levels by Keap1, which targets Nrf2 for redox-sensitive ubiquitin-mediated degradation in the cytoplasm and exports Nrf2 from the nucleus. However, it is not clear how Keap1 gains access to the nucleus. In this study, we show that Keap1 is constantly shuttling between the nucleus and the cytoplasm under physiological conditions. The nuclear import of Keap1 requires its C-terminal Kelch domain and is independent of Nrf1 and Nrf2. We have determined that importin α7, also known as karyopherin α6 (KPNA6), directly interacts with the Kelch domain of Keap1. Overexpression of KPNA6 facilitates Keap1 nuclear import and attenuates Nrf2 signaling, whereas knockdown of KPNA6 slows down Keap1 nuclear import and enhances the Nrf2-mediated adaptive response induced by oxidative stress. Furthermore, KPNA6 accelerates the clearance of Nrf2 protein from the nucleus during the postinduction phase, therefore promoting restoration of the Nrf2 protein to basal levels. These findings demonstrate that KPNA6-mediated Keap1 nuclear import plays an essential role in modulating the Nrf2-dependent antioxidant response and maintaining cellular redox homeostasis.
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