ArticleThe Journal of biological chemistry2011
Inhibitor of Nrf2 (INrf2 or Keap1) protein degrades Bcl-xL via phosphoglycerate mutase 5 and controls cellular apoptosis.
Article in The Journal of biological chemistry, 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 It has been retracted, and should not be counted.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 32 papers.
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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.
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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
32 citing papers in PubMed, 61 citations in OpenAlex.
- Deciphering the Iron Metabolism and Ferroptosis in Diabetic Wound Healing.Current diabetes reviews · 2026Review
- S100A9 Derived from Chemoembolization-Induced Hypoxia Governs Mitochondrial Function in Hepatocellular Carcinoma Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- The roles of KLHL family members in human cancers.American journal of cancer research · 2022Review
- Viral-mediated gene delivery of TMBIM6 protects the neonatal brain via disruption of NPR-CYP complex coupled with upregulation of Nrf-2 post-HI.Journal of neuroinflammation · 2019Article
- 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
- p62-Dependent Phase Separation of Patient-Derived KEAP1 Mutations and NRF2.Molecular and cellular biology · 2018Article
- High PGAM5 expression induces chemoresistance by enhancing Bcl-xL-mediated anti-apoptotic signaling and predicts poor prognosis in hepatocellular carcinoma patients.Cell death & disease · 2018Article
- Carboxyethylgermanium sesquioxide (Ge-132) treatment during in vitro culture protects fertilized porcine embryos against oxidative stress induced apoptosis.The Journal of reproduction and development · 2017Article
- Bcl-xMucosal immunology · 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
- NRF2 Is a Potential Modulator of Hyperresistance to Arsenic Toxicity in Stem-Like Keratinocytes.Oxidative medicine and cellular longevity · 2017Article
- Tert-butylhydroquinone attenuates the ethanol-induced apoptosis of and activates the Nrf2 antioxidant defense pathway in H9c2 cardiomyocytes.International journal of molecular medicine · 2016Article
- An Essential Role of NRF2 in Diabetic Wound Healing.Diabetes · 2016Article
- The Mitochondrial Phosphatase PGAM5 Is Dispensable for Necroptosis but Promotes Inflammasome Activation in Macrophages.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
- An increase in glucosylceramide synthase induces Bcl-xL-mediated cell survival in vinorelbine-resistant lung adenocarcinoma cells.Oncotarget · 2015Article
- Emerging understanding of Bcl-2 biology: Implications for neoplastic progression and treatment.Biochimica et biophysica acta · 2015Review
- Emerging functional cross-talk between the Keap1-Nrf2 system and mitochondria.Journal of clinical biochemistry and nutrition · 2015Review
- A conserved motif mediates both multimer formation and allosteric activation of phosphoglycerate mutase 5.The Journal of biological chemistry · 2014Article
- Degradation of Keap1 activates BH3-only proteins Bim and PUMA during hepatocyte lipoapoptosis.Cell death and differentiation · 2014Article
- The Marburg virus VP24 protein interacts with Keap1 to activate the cytoprotective antioxidant response pathway.Cell reports · 2014Article
Corrections and comments
- Retraction · 2014-08-08Notice - Limited or No Information · · 1. Article withdrawn by authors
- Retracted
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
INrf2 (Keap1) is an adaptor protein that facilitates INrf2-Cul3-Rbx1-mediated ubiquitination/degradation of Nrf2, a master regulator of cytoprotective gene expression. Here, we present evidence that members of the phosphoglycerate mutase family 5 (PGAM5) proteins are involved in the INrf2-mediated ubiquitination/degradation of anti-apoptotic factor Bcl-xL. Mass spectrometry and co-immunoprecipitation assays revealed that INrf2, through its DGR domain, interacts with PGAM5, which in turn interacts with anti-apoptotic Bcl-xL protein. INrf2-Cul3-Rbx1 complex facilitates ubiquitination and degradation of both PGAM5 and Bcl-xL. Overexpression of PGAM5 protein increased INrf2-mediated degradation of Bcl-xL, whereas knocking down PGAM5 by siRNA decreased INrf2 degradation of Bcl-xL, resulting in increased stability of Bcl-xL. Mutation of PGMA5-E79A/S80A abolished INrf2/PGAM5/Bcl-xL interaction. Therefore, PGAM5 protein acts as a bridge between INrf2 and Bcl-xL interaction. Further studies showed that overexpression of INrf2 enhanced degradation of PGAM5-Bcl-xL complex, led to etoposide-mediated accumulation of Bax, increased release of cytochrome c from mitochondria, activated caspase-3/7, and enhanced DNA fragmentation and apoptosis. In addition, antioxidant (tert-butylhydroquinone) treatment destabilized the Nrf2-INrf2-PGAM5-Bcl-xL complex, which resulted in release of Nrf2 in cytosol and mitochondria, release of Bcl-xL in mitochondria, increase in Bcl-xL heterodimerization with Bax in mitochondria, and reduced cellular apoptosis. These data provide the first evidence that INrf2 controls Bcl-xL via PGAM5 and controls cellular apoptosis.
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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.