ArticleRedox biology2023
The NRF2-p97-NRF2 negative feedback loop.
Article in Redox biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
14 citing papers in PubMed, 20 citations in OpenAlex.
- The Role of Nuclear Factor Erythroid 2-Related Factor 2 in the Crosstalk Between Oxidative Stress and M1/M2 Microglial Polarization Following Ischemic Stroke.Molecular neurobiology · 2026Review
- The NRF2 signaling pathway in hepatocellular carcinoma: dual roles, epigenetic reprogramming, and therapeutic opportunities in metabolic vulnerability.Frontiers in oncology · 2026Review
- Integrated computational and experimental approach to identify Nrf2-regulated molecular targets in cerebral ischemia.Pharmacological reports : PR · 2025Article
- Thirty years of NRF2: advances and therapeutic challenges.Nature reviews. Drug discovery · 2025Review
- Review
- ELANE enhances KEAP1 protein stability and reduces NRF2-mediated ferroptosis inhibition in metabolic dysfunction-associated fatty liver disease.Cell death & disease · 2025Article
- Pharmacological targeting of the mitochondrial phosphatase PTPMT1 sensitizes hepatocellular carcinoma to ferroptosis.Cell death & disease · 2025Article
- Redox-Induced Stabilization of AMBRA1 by USP7 Promotes Intestinal Oxidative Stress and Colitis Through Antagonizing DUB3-Mediated NRF2 Deubiquitination.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Gaudichaudione H Enhances the Sensitivity of Hepatocellular Carcinoma Cells to Disulfidptosis via Regulating NRF2-SLC7A11 Signaling Pathway.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The contrasting regulatory effects of valproic acid on ferroptosis and disulfidptosis in hepatocellular carcinoma.Theranostics · 2025Article
- Isolation, purification, and characterization of polysaccharides fromFrontiers in nutrition · 2025Article
- Promising tools into oxidative stress: A review of non-rodent model organisms.Redox biology · 2024Review
- Inhalation of particulate matter containing environmentally persistent free radicals induces endothelial dysfunction mediated via AhR activation at the air-blood interface.Toxicological sciences : an official journal of the Society of Toxicology · 2024Article
- Nuclear factor erythroid 2-related factor 2 as targets to treat chronic obstructive pulmonary disease: toward new perspectives.Therapeutic advances in respiratory diseaseReview
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
p97 is a ubiquitin-targeted ATP-dependent segregase that regulates proteostasis, in addition to a variety of other cellular functions. Previously, we demonstrated that p97 negatively regulates NRF2 by extracting ubiquitylated NRF2 from the KEAP1-CUL3-RBX1 E3 ubiquitin ligase complex, facilitating proteasomal destruction. In the current study, we identified p97 as an NRF2-target gene that contains a functional ARE, indicating the presence of an NRF2-p97-NRF2 negative feedback loop that maintains redox homeostasis. Using CRISPR/Cas9 genome editing, we generated endogenous p97 ARE-mutated BEAS-2B cell lines. These p97 ARE-mutated cell lines exhibit altered expression of p97 and NRF2, as well as a compromised response to NRF2 inducers. Importantly, we also found a positive correlation between NRF2 activation and p97 expression in human cancer patients. Finally, using chronic arsenic-transformed cell lines, we demonstrated a synergistic effect of NRF2 and p97 inhibition in killing cancer cells with high NRF2 and p97 expression. Our study suggests dual upregulation of NRF2 and p97 occurs in certain types of cancers, suggesting that inhibition of both NRF2 and p97 could be a promising treatment strategy for stratified cancer patients.
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Registered trials
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.