ArticleScientific reports2017
Activation of PERK-Nrf2 oncogenic signaling promotes Mdm2-mediated Rb degradation in persistently infected HCV culture.
Article in Scientific reports, 2017. 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 It has been retracted, and should not be counted.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 18 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.
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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
18 citing papers in PubMed, 28 citations in OpenAlex.
- Influence of Inhibition of COX-2-Dependent Lipid Metabolism on Regulation of UVB-Induced Keratinocytes Apoptosis by Cannabinoids.Biomolecules · 2022Article
- Article
- Extracellular Vesicle Release Promotes Viral Replication during Persistent HCV Infection.Cells · 2021Article
- Article
- Molecular Mechanisms Underlying Hepatocellular Carcinoma Induction by Aberrant NRF2 Activation-Mediated Transcription Networks: Interaction of NRF2-KEAP1 Controls the Fate of Hepatocarcinogenesis.International journal of molecular sciences · 2020Review
- Integrated stress response in hepatitis C promotes Nrf2-related chaperone-mediated autophagy: A novel mechanism for host-microbe survival and HCC development in liver cirrhosis.Seminars in cell & developmental biology · 2020Review
- Involvement of Metabolic Lipid Mediators in the Regulation of Apoptosis.Biomolecules · 2020Review
- The role of MDM2-p53 axis dysfunction in the hepatocellular carcinoma transformation.Cell death discovery · 2020Review
- Hepatocellular Carcinoma Mechanisms Associated with Chronic HCV Infection and the Impact of Direct-Acting Antiviral Treatment.Journal of hepatocellular carcinoma · 2020Review
- Silicon dioxide nanoparticles induce insulin resistance through endoplasmic reticulum stress and generation of reactive oxygen species.Particle and fibre toxicology · 2019Article
- Review
- Article
- Japanese Encephalitis Virus Induces Apoptosis and Encephalitis by Activating the PERK Pathway.Journal of virology · 2019Article
- The Potential Role of Nrf2 Signaling in Leishmania Infection Outcomes.Frontiers in cellular and infection microbiology · 2019Review
- Chaperone-Mediated Autophagy Promotes Beclin1 Degradation in Persistently Infected Hepatitis C Virus Cell Culture.The American journal of pathology · 2018Article
- NRF2 and the Hallmarks of Cancer.Cancer cell · 2018Review
- Curcumin mitigates axonal injury and neuronal cell apoptosis through the PERK/Nrf2 signaling pathway following diffuse axonal injury.Neuroreport · 2018Article
- Adapted HCV JFH1 variant is capable of accommodating a large foreign gene insert and allows lower level HCV replication and viral production.International journal of biological sciences · 2018Article
Corrections and comments
- Retraction · 2021-09-01Concerns/Issues about Data · Duplication of/in Image · Original Data and/or Images not Provided and/or not Available · Unreliable Data · · see also: https://pubpeer.com/publications/DFCCF96E8E2F7BD126C9FE01665F52; Suchitra Sumitran-Holgersson has institutional finding of misconduct;
- Retracted
Authors and funding
12 authors at 6 institutions in 2 countries.
Funding
Abstract
The mechanism of how chronic hepatitis C virus (HCV) infection leads to such a high rate of hepatocellular carcinoma (HCC) is unknown. We found that the PERK axis of endoplasmic reticulum (ER) stress elicited prominent nuclear translocation of Nrf2 in 100% of HCV infected hepatocytes. The sustained nuclear translocation of Nrf2 in chronically infected culture induces Mdm2-mediated retinoblastoma protein (Rb) degradation. Silencing PERK and Nrf2 restored Mdm2-mediated Rb degradation, suggesting that sustained activation of PERK/Nrf2 axis creates oncogenic stress in chronically infected HCV culture model. The activation of Nrf2 and its nuclear translocation were prevented by ER-stress and PERK inhibitors, suggesting that PERK axis is involved in the sustained activation of Nrf2 signaling during chronic HCV infection. Furthermore, we show that HCV clearance induced by interferon-α based antiviral normalized the ER-stress response and prevented nuclear translocation of Nrf2, whereas HCV clearance by DAAs combination does neither. In conclusion, we report here a novel mechanism for how sustained activation of PERK axis of ER-stress during chronic HCV infection activates oncogenic Nrf2 signaling that promotes hepatocyte survival and oncogenesis by inducing Mdm2-mediated Rb degradation.
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What OpenQuestion holds
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.