ArticleProceedings of the National Academy of Sciences of the United States of America2012
Hepatitis B virus X protein targets the Bcl-2 protein CED-9 to induce intracellular Ca2+ increase and cell death in Caenorhabditis elegans.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. 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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Who cites it
32 citing papers in PubMed, 54 citations in OpenAlex.
- Nonapoptotic role of EGL-1 in exopher production and neuronal health inProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Hepatitis B virus genotypes A1 and A2 have distinct replication phenotypes due to polymorphisms in the HBx gene.PLoS pathogens · 2025Article
- SMC5/6-Mediated Transcriptional Regulation of Hepatitis B Virus and Its Therapeutic Potential.Viruses · 2024Review
- Non-apoptotic role of EGL-1 in exopher production and neuronal health inbioRxiv : the preprint server for biology · 2024Article
- Immunoinformatics and Evaluation of Peptide Vaccines Derived from Global Hepatitis B Viral HBx and HBc Proteins Critical for Covalently Closed Circular DNA Integrity.Microorganisms · 2023Article
- Coronavirus Porcine Epidemic Diarrhea Virus Utilizes Chemokine Interleukin-8 to Facilitate Viral Replication by Regulating CaJournal of virology · 2023Article
- The role of hepatitis B virus genome variations in HBV-related HCC: effects on host signaling pathways.Frontiers in microbiology · 2023Review
- Live or death in cells: from micronutrition metabolism to cell fate.Frontiers in cell and developmental biology · 2023Review
- Compartmentalisation of Hepatitis B virus X gene evolution in hepatocellular carcinoma microenvironment and the genotype-phenotype correlation of tumorigenicity in HBV-related patients with hepatocellular carcinoma.Emerging microbes & infections · 2022Article
- Inhibition of histone H3-H4 chaperone pathways rescues C. elegans sterility by H2B loss.PLoS genetics · 2022Article
- Nonsynonymous C1653T Mutation of Hepatitis B Virus X Gene Enhances Malignancy of Hepatocellular Carcinoma Cells.Journal of hepatocellular carcinoma · 2022Article
- Canonical and Divergent N-Terminal HBx Isoform Proteins Unveiled: Characteristics and Roles during HBV Replication.Biomedicines · 2021Article
- Calcium signaling in hepatitis B virus infection and its potential as a therapeutic target.Cell communication and signaling : CCS · 2021Review
- Screening of the HBx transactivation domain interacting proteins and the function of interactor Pin1 in HBV replication.Scientific reports · 2021Article
- Structural and functional analyses of hepatitis B virus X protein BH3-like domain and Bcl-xL interaction.Nature communications · 2019Article
- Dysregulation of Nrf2 in Hepatocellular Carcinoma: Role in Cancer Progression and Chemoresistance.Cancers · 2018Review
- Duck enteritis virus activates CaMKKβ-AMPK to trigger autophagy in duck embryo fibroblast cells via increased cytosolic calcium.Virology journal · 2018Article
- Hepatitis B Virus X Protein Upregulates Intracellular Calcium Signaling by Binding C-terminal of Orail Protein.Current medical science · 2018Article
- Capable Infection of Hepatitis B Virus in Diffuse Large B-cell Lymphoma.Journal of Cancer · 2018Article
- Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
Abstract
HBx is a multifunctional hepatitis B virus (HBV) protein that is crucial for HBV infection and pathogenesis and a contributing cause of hepatocyte carcinogenesis. However, the host targets and mechanisms of action of HBx are poorly characterized. We show here that expression of HBx in Caenorhabditis elegans induces both necrotic and apoptotic cell death, mimicking an early event of liver infection by HBV. Genetic and biochemical analyses indicate that HBx interacts directly with the B-cell lymphoma 2 (Bcl-2) homolog CED-9 (cell death abnormal) through a Bcl-2 homology 3 (BH3)-like motif to trigger both cytosolic Ca(2+) increase and cell death. Importantly, Bcl-2 can substitute for CED-9 in mediating HBx-induced cell killing in C. elegans, suggesting that CED-9 and Bcl-2 are conserved cellular targets of HBx. A genetic suppressor screen of HBx-induced cell death has produced many mutations, including mutations in key regulators from both apoptosis and necrosis pathways, indicating that this screen can identify new apoptosis and necrosis genes. Our results suggest that C. elegans could serve as an animal model for identifying crucial host factors and signaling pathways of HBx and aid in development of strategies to treat HBV-induced liver disorders.
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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.