ArticleMolecular and cellular biology2016
The Mediator Subunit MED16 Transduces NRF2-Activating Signals into Antioxidant Gene Expression.
Article in Molecular and cellular biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 93 citations in OpenAlex.
- Genetic ancestry and genotype-by-diet interactions shape plasma carotenoid metabolism in humans.Research square · 2026Article
- Interplay between NRF2 post-translational modifications and protein-protein interactions: Perspectives from emerging structural and functional evidence.Archives of biochemistry and biophysics · 2026Review
- Beyond KEAP1: The Context-Specific NRF2 Partner Code in Disease and Therapy.Antioxidants (Basel, Switzerland) · 2026Review
- A phosphorylation switch in the Mediator MED15 controls cellular senescence and cognitive decline.Cell discovery · 2025Article
- The Gut Microbiota Metabolite Urolithin B Mitigates Cholestatic Liver Injury in Mice via Modulating the Crosstalk Between PPARα, Nrf2, and NF-κB Signaling Pathways.Journal of xenobiotics · 2025Article
- NRF2 supports non-small cell lung cancer growth independently of CBP/p300-enhanced glutathione synthesis.EMBO reports · 2025Article
- Targeting epigenetic and post-translational modifications of NRF2: key regulatory factors in disease treatment.Cell death discovery · 2025Review
- Bi-allelic MED16 variants cause a MEDopathy with intellectual disability, motor delay, and craniofacial, cardiac, and limb malformations.American journal of human genetics · 2025Article
- New insights into coordinated regulation of AHR promoter transcription; molecular mechanisms and therapeutic targets.International journal of biological sciences · 2025Review
- Petunidin alleviates diabetic nephropathy injury via the inhibition of oxidative stress and ferroptosis through the Keap1/mitoNQO1 pathway.Frontiers in cell and developmental biology · 2025Article
- Common and rare genetic variation intersects with ancestry to influence human skin and plasma carotenoid concentrations.medRxiv : the preprint server for health sciences · 2024Article
- Nrf2-Keap1 in Cardiovascular Disease: Which Is the Cart and Which the Horse?Physiology (Bethesda, Md.) · 2024Review
- Ferroptosis regulation by Cap'n'collar family transcription factors.The Journal of biological chemistry · 2024Review
- Protective Effects of Hepatocyte Stress Defenders, Nrf1 and Nrf2, against MASLD Progression.International journal of molecular sciences · 2024Article
- Unique and overlapping roles of NRF2 and NRF1 in transcriptional regulation.Journal of clinical biochemistry and nutrition · 2024Article
- Revisiting the role of hypoxia-inducible factors and nuclear factor erythroid 2-related factor 2 in regulating macrophage inflammation and metabolism.Frontiers in cellular and infection microbiology · 2024Review
- Proximity proteomic analysis of the NRF family reveals the Parkinson's disease protein ZNF746/PARIS as a co-complexed repressor of NRF2.Science signaling · 2023Article
- Compact engineered human mechanosensitive transactivation modules enable potent and versatile synthetic transcriptional control.Nature methods · 2023Article
- How to deal with frenemy NRF2: Targeting NRF2 for chemoprevention and cancer therapy.Journal of food and drug analysis · 2023Review
- The anti-inflammatory and anti-oxidative effect of a classical hypnotic bromovalerylurea mediated by the activation of NRF2.Journal of biochemistry · 2023Article
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The KEAP1-NRF2 system plays a central role in cytoprotection. NRF2 is stabilized in response to electrophiles and activates transcription of antioxidant genes. Although robust induction of NRF2 target genes confers resistance to oxidative insults, how NRF2 triggers transcriptional activation after binding to DNA has not been elucidated. To decipher the molecular mechanisms underlying NRF2-dependent transcriptional activation, we purified the NRF2 nuclear protein complex and identified the Mediator subunits as NRF2 cofactors. Among them, MED16 directly associated with NRF2. Disruption of Med16 significantly attenuated the electrophile-induced expression of NRF2 target genes but did not affect hypoxia-induced gene expression, suggesting a specific requirement for MED16 in NRF2-dependent transcription. Importantly, we found that 75% of NRF2-activated genes exhibited blunted inductions by electrophiles in Med16-deficient cells compared to wild-type cells, which strongly argues that MED16 is a major contributor supporting NRF2-dependent transcriptional activation. NRF2-dependent phosphorylation of the RNA polymerase II C-terminal domain was absent in Med16-deficient cells, suggesting that MED16 serves as a conduit to transmit NRF2-activating signals to RNA polymerase II. MED16 indeed turned out to be essential for cytoprotection against oxidative insults. Thus, the KEAP1-NRF2-MED16 axis has emerged as a new regulatory pathway mediating the antioxidant response through the robust activation of NRF2 target genes.
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