ArticleThe Journal of biological chemistry2015
Apurinic/apyrimidinic endonuclease/redox factor-1 (APE1/Ref-1) redox function negatively regulates NRF2.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.
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Who cites it
47 citing papers in PubMed, 1 synthesis or guideline pooled it, 75 citations in OpenAlex.
- Dual roles and therapeutic potential of Keap1-Nrf2 pathway in pancreatic cancer: a systematic review.Cell communication and signaling : CCS · 2019Pooled it
- APEX1 attenuates myocardial ischemia-reperfusion injury by inhibiting ferroptosis via the Nrf2/GPX4 signaling pathway.Molecular biology reports · 2026Article
- Localized heme sensing through a ternary molecular glue.bioRxiv : the preprint server for biology · 2026Article
- APE1/Ref-1 inhibition via APX3330 lowers monocyte/macrophage infiltration without ameliorating the structure and function of dystrophic mdx hindlimb muscles.Physiological reports · 2025Article
- NRF2 Antioxidant Response and Interferon-Stimulated Genes Are Differentially Expressed in SARS-CoV-2-Positive Young Subjects.Immunity, inflammation and disease · 2025Article
- The APE1/REF-1 and the hallmarks of cancer.Molecular biology reports · 2024Review
- AP endonuclease 1: Biological updates and advances in activity analysis.Methods in enzymology · 2024Article
- Regulatory factors of Nrf2 in age-related macular degeneration pathogenesis.International journal of ophthalmology · 2024Review
- SARS-CoV-2 infection and dysregulation of nuclear factor erythroid-2-related factor 2 (Nrf2) pathway.Cell stress & chaperones · 2023Review
- Revisiting Two Decades of Research Focused on Targeting APE1 for Cancer Therapy: The Pros and Cons.Cells · 2023Review
- Identification of Novel Pathways Regulated by APE1/Ref-1 in Human Retinal Endothelial Cells.International journal of molecular sciences · 2023Article
- Activation of the integrated stress response (ISR) pathways in response to Ref-1 inhibition in human pancreatic cancer and its tumor microenvironment.Frontiers in medicine · 2023Article
- Is Autophagy Always a Barrier to Cisplatin Therapy?Biomolecules · 2022Review
- RelA Is an Essential Target for Enhancing Cellular Responses to the DNA Repair/Ref-1 Redox Signaling Protein and Restoring Perturbated Cellular Redox Homeostasis in Mouse PDAC Cells.Frontiers in oncology · 2022Article
- A graph neural network model to estimate cell-wise metabolic flux using single-cell RNA-seq data.Genome research · 2021Article
- Inhibition of APE1/Ref-1 for Neovascular Eye Diseases: From Biology to Therapy.International journal of molecular sciences · 2021Review
- Ref-1 redox activity alters cancer cell metabolism in pancreatic cancer: exploiting this novel finding as a potential target.Journal of experimental & clinical cancer research : CR · 2021Article
- Exploring transcriptional regulators Ref-1 and STAT3 as therapeutic targets in malignant peripheral nerve sheath tumours.British journal of cancer · 2021Article
- Merlin deficiency alters the redox management program in breast cancer.Molecular oncology · 2021Article
- Role of Reductive versus Oxidative Stress in Tumor Progression and Anticancer Drug Resistance.Cells · 2021Review
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 3 countries.
Funding
Abstract
Apurinic/apyrimidinic endonuclease/redox factor-1 (APE1/Ref-1) (henceforth referred to as Ref-1) is a multifunctional protein that in addition to its base excision DNA repair activity exerts redox control of multiple transcription factors, including nuclear factor κ-light chain enhancer of activated B cells (NF-κB), STAT3, activator protein-1 (AP-1), hypoxia-inducible factor-1 (HIF-1), and tumor protein 53 (p53). In recent years, Ref-1 has emerged as a promising therapeutic target in cancer, particularly in pancreatic ductal carcinoma. Although a significant amount of research has centered on Ref-1, no wide-ranging approach had been performed on the effects of Ref-1 inhibition and transcription factor activity perturbation. Starting with a broader approach, we identified a previously unsuspected effect on the nuclear factor erythroid-related factor 2 (NRF2), a critical regulator of cellular defenses against oxidative stress. Based on genetic and small molecule inhibitor-based methodologies, we demonstrated that repression of Ref-1 potently activates NRF2 and its downstream targets in a dose-dependent fashion, and that the redox, rather than the DNA repair function of Ref-1 is critical for this effect. Intriguingly, our results also indicate that this pathway does not involve reactive oxygen species. The link between Ref-1 and NRF2 appears to be present in all cells tested in vitro, noncancerous and cancerous, including patient-derived tumor samples. In particular, we focused on understanding the implications of the novel interaction between these two pathways in primary pancreatic ductal adenocarcinoma tumor cells and provide the first evidence that this mechanism has implications for overcoming the resistance against experimental drugs targeting Ref-1 activity, with clear translational implications.
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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.