ArticleThe Journal of biological chemistry2014
Modulation of nuclear factor E2-related factor-2 (Nrf2) activation by the stress response gene immediate early response-3 (IER3) in colonic epithelial cells: a novel mechanism of cellular adaption to inflammatory stress.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.
- The NRF2 transcription factor plays a dual role in colorectal cancer: A systematic review.PloS one · 2017Pooled it
- Mechanism-based prediction of drug synergy via network controllability analysis of therapeutic pathways in intractable diseases.iScience · 2026Article
- IER3 Promotes Malignant Progression of Colorectal Cancer Through the NF-International journal of genomics · 2026Article
- Nrf2 as a Molecular Guardian of Redox Balance and Barrier Integrity in IBD.Antioxidants (Basel, Switzerland) · 2025Review
- Selenium: A Key Element in Inflammatory Bowel Disease.Antioxidants (Basel, Switzerland) · 2025Review
- Levosimendan Pretreatment Attenuates Mesenteric Artery Ischemia/Reperfusion Injury and Multi-Organ Damage in Rats.International journal of molecular sciences · 2025Article
- Identification of heterogeneity and common characteristics in colorectal carcinoma located in distinct sites.Scientific reports · 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
- Unveiling Varied Cell Death Patterns in Lung Adenocarcinoma Prognosis and Immunotherapy Based on Single-Cell Analysis and Machine Learning.Journal of cellular and molecular medicine · 2024Article
- Oxidative stress in hair follicle development and hair growth: Signalling pathways, intervening mechanisms and potential of natural antioxidants.Journal of cellular and molecular medicine · 2024Review
- Association of different inflammatory indices with risk of early natural menopause: a cross-sectional analysis of the NHANES 2013-2018.Frontiers in medicine · 2024Article
- Identification and validation of a novel glycolysis-related ceRNA network for sepsis-induced cardiomyopathy.Frontiers in medicine · 2024Article
- The emerging role of oxidative stress in inflammatory bowel disease.Frontiers in endocrinology · 2024Review
- A Review of the Potential of Nuclear Factor [Erythroid-Derived 2]-like 2 Activation in Autoimmune Diseases.Brain sciences · 2023Review
- Exploring the Impact of Cyanidin-3-Glucoside on Inflammatory Bowel Diseases: Investigating New Mechanisms for Emerging Interventions.International journal of molecular sciences · 2023Review
- The role of Nrf2 in the pathogenesis and treatment of ulcerative colitis.Frontiers in immunology · 2023Review
- Disruption of mitochondrial quality control genes promotes caspase-resistant cell survival following apoptotic stimuli.The Journal of biological chemistry · 2022Article
- Importance of Heme Oxygenase-1 in Gastrointestinal Cancers: Functions, Inductions, Regulations, and Signaling.Journal of gastrointestinal cancer · 2021Review
- Overexpression of Nrf2 promotes colon cancer progression via ERK and AKT signaling pathways.Annals of surgical treatment and research · 2020Article
- DUB3 deubiquitinates and stabilizes NRF2 in chemotherapy resistance of colorectal cancer.Cell death and differentiation · 2019Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although nuclear factor E2-related factor-2 (Nrf2) protects from carcinogen-induced tumorigenesis, underlying the rationale for using Nrf2 inducers in chemoprevention, this antioxidative transcription factor may also act as a proto-oncogene. Thus, an enhanced Nrf2 activity promotes formation and chemoresistance of colon cancer. One mechanism causing persistent Nrf2 activation is the adaptation of epithelial cells to oxidative stress during chronic inflammation, e.g. colonocytes in inflammatory bowel diseases, and the multifunctional stress response gene immediate early response-3 (IER3) has a crucial role under these conditions. We now demonstrate that colonic tissue from Ier3(-/-) mice subject of dextran sodium sulfate colitis exhibit greater Nrf2 activity than Ier3(+/+) mice, manifesting as increased nuclear Nrf2 protein level and Nrf2 target gene expression. Likewise, human NCM460 colonocytes subjected to shRNA-mediated IER3 knockdown exhibit greater Nrf2 activity compared with control cells, whereas IER3 overexpression attenuated Nrf2 activation. IER3-deficient NCM460 cells exhibited reduced reactive oxygen species levels, indicating increased antioxidative protection, as well as lower sensitivity to TRAIL or anticancer drug-induced apoptosis and greater clonogenicity. Knockdown of Nrf2 expression reversed these IER3-dependent effects. Further, the enhancing effect of IER3 deficiency on Nrf2 activity relates to the control of the inhibitory tyrosine kinase Fyn by the PI3K/Akt pathway. Thus, the PI3K inhibitor LY294002 or knockdown of Akt or Fyn expression abrogated the impact of IER3 deficiency on Nrf2 activity. In conclusion, the interference of IER3 with the PI3K/Akt-Fyn pathway represents a novel mechanism of Nrf2 regulation that may get lost in tumors and by which IER3 exerts its stress-adaptive and tumor-suppressive activity.
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