ArticleCell death and differentiation2011
INrf2 (Keap1) targets Bcl-2 degradation and controls cellular apoptosis.
Article in Cell death and differentiation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 45 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
45 citing papers in PubMed, 83 citations in OpenAlex.
- Nrf2/Keap1/ARE signaling: Towards specific regulation.Life sciences · 2022Review
- The roles of KLHL family members in human cancers.American journal of cancer research · 2022Review
- Bioactive Peptide F2d Isolated from Rice Residue Exerts Antioxidant Effects via Nrf2 Signaling Pathway.Oxidative medicine and cellular longevity · 2021Article
- Evaluation of Nrf2, Keap1 and Apoptotic Pathway Genes Expression in Acute Myeloid Leukemia Patients.Iranian journal of pharmaceutical research : IJPR · 2021Article
- Non-esterified Fatty Acid Induce Dairy Cow Hepatocytes Apoptosis via the Mitochondria-Mediated ROS-JNK/ERK Signaling Pathway.Frontiers in cell and developmental biology · 2020Article
- Downregulation of Keap1 contributes to poor prognosis and Axitinib resistance of renal cell carcinoma via upregulation of Nrf2 expression.International journal of molecular medicine · 2019Article
- Decursin induces apoptosis in glioblastoma cells, but not in glial cellsThe Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2019Article
- FGF10 Enhances Peripheral Nerve RegenerationFrontiers in pharmacology · 2019Article
- p62-Dependent Phase Separation of Patient-Derived KEAP1 Mutations and NRF2.Molecular and cellular biology · 2018Article
- Pterostilbene attenuates myocardial ischemia-reperfusion injury via the phosphatidylinositol 3'-kinase-protein kinase B signaling pathway.Experimental and therapeutic medicine · 2017Article
- Mitochondrial phosphatase PGAM5 regulates Keap1-mediated Bcl-xL degradation and controls cardiomyocyte apoptosis driven by myocardial ischemia/reperfusion injury.In vitro cellular & developmental biology. Animal · 2017Article
- Dual Roles of Oxidative Stress in Metal Carcinogenesis.Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer · 2017Review
- Progress and prospects of reactive oxygen species in metal carcinogenesis.Current pharmacology reports · 2016Article
- Tert-butylhydroquinone attenuates the ethanol-induced apoptosis of and activates the Nrf2 antioxidant defense pathway in H9c2 cardiomyocytes.International journal of molecular medicine · 2016Article
- Pharmacology and Clinical Drug Candidates in Redox Medicine.Antioxidants & redox signaling · 2015Review
- Article
- The role of transcription factor Nrf2 in skin cells metabolism.Archives of dermatological research · 2015Review
- Emerging functional cross-talk between the Keap1-Nrf2 system and mitochondria.Journal of clinical biochemistry and nutrition · 2015Review
- Involvement of Nrf2 in development of anxiety-like behavior by linking Bcl2 to oxidative phosphorylation: estimation in rat hippocampus, amygdala, and prefrontal cortex.Journal of molecular neuroscience : MN · 2015Article
- Resveratrol attenuates inflammation and oxidative stress induced by myocardial ischemia-reperfusion injury: role of Nrf2/ARE pathway.International journal of clinical and experimental medicine · 2015Article
Corrections and comments
- Retraction · 2013-12-13Duplication of/in Image ·
- Retracted
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Cytosolic inhibitor of Nrf2 (INrf2) is an adaptor protein that mediates ubiquitination/degradation of NF-E2-related factor 2 (Nrf2), a master regulator of cytoprotective gene expression. In this paper, we demonstrate that INrf2 degrades endogenous antiapoptotic B-cell CLL/lymphoma 2 (Bcl-2) protein and controls cellular apoptosis. The DGR domain of INrf2 interacts with the BH2 domain of Bcl-2 and facilitates INrf2:Cul3-Rbx1-mediated ubiquitination of Bcl-2 by the conjugation of ubiquitin molecules to lysine17 of Bcl-2. Further studies showed that INrf2 enhanced etoposide-mediated accumulation of Bax, increased release of cytochrome c from mitochondria, activated caspase-3/7, and enhanced DNA fragmentation and apoptosis. Antioxidants antagonized Bcl-2:INrf2 interaction, led to the release and stabilization of Bcl-2, increased Bcl-2:Bax heterodimers and reduced apoptosis. Moreover, dysfunctional/mutant INrf2 in human lung cancer cells failed to degrade Bcl-2, resulting in decreased etoposide and UV/γ radiation-mediated DNA fragmentation. These data provide the first evidence of INrf2 control of Bcl-2 and apoptotic cell death, with implications in antioxidant protection, survival of cancer cells containing dysfunctional INrf2, and drug resistance.
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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.