ArticlePloS one2015
Hepatitis B Virus X Protein Sensitizes TRAIL-Induced Hepatocyte Apoptosis by Inhibiting the E3 Ubiquitin Ligase A20.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. 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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Who cites it
18 citing papers in PubMed, 30 citations in OpenAlex.
- The Dual Role of A20 (TNFAIP3) in Viral Infection: A Context-Dependent Regulator of Immunity and Pathogenesis.Viruses · 2025Review
- Dysregulated microRNAs as a biomarker for diagnosis and prognosis of hepatitis B virus-associated hepatocellular carcinoma.World journal of gastroenterology · 2023Review
- Apoptosis and Phagocytosis as Antiviral Mechanisms.Sub-cellular biochemistry · 2023Article
- Review
- HBx promotes hepatocarcinogenesis by enhancing phosphorylation and blocking ubiquitinylation of UHRF2.Hepatology international · 2021Article
- Specificity in Ubiquitination Triggered by Virus Infection.International journal of molecular sciences · 2020Review
- Review
- The interaction of hepatitis B virus with the ubiquitin proteasome system in viral replication and associated pathogenesis.Virology journal · 2019Review
- Role of HBx in hepatitis B virus persistence and its therapeutic implications.Current opinion in virology · 2018Review
- DR5-Cbl-b/c-Cbl-TRAF2 complex inhibits TRAIL-induced apoptosis by promoting TRAF2-mediated polyubiquitination of caspase-8 in gastric cancer cells.Molecular oncology · 2017Article
- Virus Infection and Death Receptor-Mediated Apoptosis.Viruses · 2017Review
- Interference of Apoptosis by Hepatitis B Virus.Viruses · 2017Review
- Association of the tandem polymorphisms (rs148314165, rs200820567) in TNFAIP3 with chronic hepatitis B virus infection in Chinese Han population.Virology journal · 2017Article
- Elevated serum A20 is associated with severity of chronic hepatitis B and A20 inhibits NF-κB-mediated inflammatory response.Oncotarget · 2017Article
- Altered expression of A20 gene in peripheral blood mononuclear cells is associated with the progression of chronic hepatitis B virus infection.Oncotarget · 2016Article
- Hepatitis B Virus X Protein and Hepatocarcinogenesis.International journal of molecular sciences · 2016Review
- Mechanism of Hepatocyte Apoptosis.Journal of cell death · 2016Review
- Increased A20 mRNA Level in Peripheral Blood Mononuclear Cells is Associated With Immune Phases of Patients With Chronic Hepatitis B.Medicine · 2015Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatitis B virus (HBV) infection causes hepatocyte death and liver damage, which may eventually lead to cirrhosis and liver cancer. Hepatitis B virus X protein (HBx) is a key antigen that is critically involved in HBV-associated liver diseases. However, the molecular basis for its pathogenesis, particularly in liver damage, has not been well defined. Herein, we report that HBx was able to enhance the susceptibility of hepatocytes to TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. Increased sensitivity to TRAIL was associated with HBx-induced upregulation of miR-125a, which, in turn, suppressed the expression of its putative target gene, A20 E3 ligase. Importantly, we demonstrate that the defective expression of A20 impaired the K63-linked polyubiquitination of caspase-8, which reciprocally enhanced the activation of caspase-8, the recruitment of Fas-associated death domain (FADD), and the formation of death-inducing signaling complex (DISC), thereby promoting HBx-mediated apoptotic signaling. Accordingly, antagonizing miR-125a or ectopically expressing A20 in hepatocytes abolished the pro-apoptotic effect of HBx. Conversely, the overexpression of miR-125a or knockdown of A20 mimicked HBx to enhance TRAIL susceptibility in hepatocytes. Thus, we establish, for the first time, a miR-125a/A20-initiated and caspase-8-targeted mechanism by which HBx modulates apoptotic signaling and increases hepatic susceptibility to the damaging agent, which might provide novel insight into HBV-related liver pathology.
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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.