ArticleAntioxidants & redox signaling2016
TAK1 Regulates the Nrf2 Antioxidant System Through Modulating p62/SQSTM1.
Article in Antioxidants & redox signaling, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.
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Who cites it
48 citing papers in PubMed, 1 synthesis or guideline pooled it, 80 citations in OpenAlex.
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)Autophagy · 2021Guideline
- Review
- Butyrate protects against Klebsiella pneumoniae-induced oxidative stress in alveolar macrophages via p62-Keap1-Nrf2 pathway.Redox biology · 2026Article
- The oncogenic signalosome: SQSTM1/p62 as a master integrator of signaling, metabolism, and autophagy in cancer.Toxicological research · 2026Review
- Post-translational modifications of selective autophagy receptors: orchestrating cellular homeostasis, disease pathogenesis, and therapeutic opportunities.Cellular & molecular biology letters · 2026Review
- Review
- Unveiling the physiological impact of ESCRT-dependent autophagosome closure by targeting the VPS37A ubiquitin E2 variant-like domain.Cell reports · 2024Article
- Activation of GABAAntioxidants (Basel, Switzerland) · 2024Article
- USP8 prevents aberrant NF-κB and Nrf2 activation by counteracting ubiquitin signals from endosomes.The Journal of cell biology · 2024Article
- Ferroptosis regulation through Nrf2 and implications for neurodegenerative diseases.Archives of toxicology · 2024Review
- TAK1 inhibition mitigates intracerebral hemorrhage-induced brain injury through reduction of oxidative stress and neuronal pyroptosis via the NRF2 signaling pathway.Frontiers in immunology · 2024Article
- Gut redox and microbiome: charting the roadmap to T-cell regulation.Frontiers in immunology · 2024Review
- The master antioxidant defense is activated during EBV latent infection.Journal of virology · 2023Article
- Notoginsenoside R1 protects against myocardial ischemia/reperfusion injury in mice via suppressing TAK1-JNK/p38 signaling.Acta pharmacologica Sinica · 2023Article
- Emerging role of TAK1 in the regulation of skeletal muscle mass.BioEssays : news and reviews in molecular, cellular and developmental biology · 2023Review
- Effect of autophagy on ferroptosis in foam cells via Nrf2.Molecular and cellular biochemistry · 2022Article
- Review
- Glucose Activates Lysine-Specific Demethylase 1 through the KEAP1/p62 Pathway.Antioxidants (Basel, Switzerland) · 2021Article
- GPR30 Activation by 17β-Estradiol Promotes p62 Phosphorylation and Increases Estrogen Receptor α Protein Expression by Inducing Its Release from a Complex Formed with KEAP1.Journal of personalized medicine · 2021Article
- Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 2 countries.
Funding
Abstract
aimsNuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2) is the master transcriptional regulator of antioxidant gene expression. On increased oxidative stress, an adaptor for Nrf2 degradation, Kelch-like ECH-associated protein 1 (Keap1), is directly modulated by oxidants in the cytoplasm, which results in stabilization and activation of Nrf2. Nrf2 is also constitutively active, to some extent, in the absence of exogenous oxidative stress. We have previously demonstrated that intestinal epithelium-specific TGF-β-activated kinase 1 (TAK1) deletion downregulates the level of Nrf2 protein, resulting in an increase of reactive oxygen species (ROS) in a mouse model. We aim at determining the mechanism by which TAK1 modulates the level of Nrf2.
resultsWe found that TAK1 upregulated serine 351 phosphorylation of an autophagic adaptor protein, p62/Sequestosome-1 (SQSTM1), which facilitates interaction between p62/SQSTM1 and Keap1 and subsequent Keap1 degradation. This, ultimately, causes increased Nrf2. Tak1 deficiency reduced the phosphorylation of p62/SQSTM1, resulting in decreased steady-state levels of Nrf2 along with increased Keap1. We also found that this regulation is independent of the canonical redox-mediated Nrf2 activation mechanism. In Tak1-deficient intestinal epithelium, a synthetic phenolic electrophile, butylated hydroxyanisole still effectively upregulated Nrf2 and reduced ROS. INNOVATION: Our results identify for the first time that TAK1 is a modulator of p62/SQSTM1-dependent Keap1 degradation and maintains the steady state-level of Nrf2.
conclusionTAK1 regulates Nrf2 through modulation of Keap-p62/SQSTM1 interaction. This regulation is important for homeostatic antioxidant protection in the intestinal epithelium. Antioxid. Redox Signal. 25, 953-964.
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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.