ArticleJournal of virology2017
HDM2 Promotes NEDDylation of Hepatitis B Virus HBx To Enhance Its Stability and Function.
Article in Journal of virology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed.
- The PTM switches of HBx: Master regulators of HBV infection and liver oncogenesis.Virus research · 2026Review
- FGFR signaling and neddylation facilitate SARS-CoV-2 infection by modulating interferon induction and viral entry, respectively.iScience · 2026Article
- Decoding neddylation in malignancies: molecular mechanisms, biological functions, therapeutic resistance, and clinical potential.Cell death & disease · 2026Review
- Ubiquitination dynamics in human tumour viruses: Viral infection, oncogenesis and antiviral therapy.The FEBS journal · 2026Review
- UBE2M inhibits neoplastic cell proliferation via MKK7-JNK-EGR1 axis in melanoma.Journal of translational medicine · 2025Article
- The neddylation of the RNA-dependent RNA polymerase 3D of Coxsackievirus B3 promotes viral replication.Journal of virology · 2025Article
- Deciphering the roles of neddylation modification in hepatocellular carcinoma: Molecular mechanisms and targeted therapeutics.Genes & diseases · 2025Review
- Neddylation modification stabilizes LC3B by antagonizing its ubiquitin-mediated degradation and promoting autophagy in skin.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The Malignant Transformation of Viral Hepatitis to Hepatocellular Carcinoma: Mechanisms and Interventions.MedComm · 2025Review
- Ubiquitination of NS1 Confers Differential Adaptation of Zika Virus in Mammalian Hosts and Mosquito Vectors.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Protein neddylation and its role in health and diseases.Signal transduction and targeted therapy · 2024Review
- Polyubiquitylated rice stripe virus NS3 translocates to the nucleus to promote cytosolic virus replication via miRNA-induced fibrillin 2 upregulation.PLoS pathogens · 2024Article
- Role of Hippo pathway dysregulation from gastrointestinal premalignant lesions to cancer.Journal of translational medicine · 2024Review
- Effects of neddylation on viral infection: an overview.Archives of virology · 2023Review
- Mitochondrial Glycerol-3-Phosphate Dehydrogenase Restricts HBV Replication via the TRIM28-Mediated Degradation of HBx.Journal of virology · 2023Article
- HBx and YAP expression could promote tumor development and progression in HBV-related hepatocellular carcinoma.Biochemistry and biophysics reports · 2022Article
- Dual role of neddylation in transcription of hepatitis B virus RNAs from cccDNA and production of viral surface antigen.JHEP reports : innovation in hepatology · 2022Article
- Neddylation of Enterovirus 71 VP2 Protein Reduces Its Stability and Restricts Viral Replication.Journal of virology · 2022Article
- Blocking neddylation elicits antiviral effect against hepatitis B virus replication.Molecular biology reports · 2022Article
- The roles of E3 ligases in Hepatocellular carcinoma.American journal of cancer research · 2022Review
Corrections and comments
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Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatitis B virus (HBV)-encoded X protein (HBx) plays a critical role in HBV-related hepatocarcinoma development. In this study, we demonstrate that HBx is specifically modified by NEDD8. We found that E3 ligase HDM2 promotes NEDDylation of HBx to enhance HBx stability by preventing its ubiquitination-mediated degradation. Consistently, analysis of 160 hepatocellular carcinoma patient specimens indicated that the amount of HDM2 protein correlates with HBx protein level. We identified that HBx K91 and K95 as the key HBx NEDDylation sites and observed that the NEDDylation-deficient HBx has shorter half-life. We generated Huh7 cell lines which ectopically express wild-type and NEDDylation-deficient HBx and found that NEDDylation-deficient HBx showed less chromatin localization and less DDB1 binding. Consistently, the expression of HBx-regulated genes (IL-8, MMP9, and YAP) and HBV transcription (the activity of HBV enhancer and the amount of pgRNA transcribed from cccDNA) were significantly higher in cells expressing wild-type (WT) HBx than that in cells expressing mutant HBx. In addition, HBx-expressing cells proliferated faster than control and mutant HBx-expressing cells. We also showed that the ability of WT HBx-expressing cells to form tumors in nude mice was significantly higher than that of mutant HBx-expressing cells. In conclusion, we revealed that E3 ligase HDM2 promotes NEDDylation of HBx to enhance HBx stability and chromatin localization, which in turn favors HBx-dependent transcriptional regulation, cell proliferation, and HBV-driven tumor growth.
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Registered trials
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