ArticleMolecular and cellular biology1999
Direct association and nuclear import of the hepatitis B virus X protein with the NF-kappaB inhibitor IkappaBalpha.
Article in Molecular and cellular biology, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 130 citations in OpenAlex.
- New Insights into the Role of NF-κB in Hepatitis B Virus Infection.International journal of biological sciences · 2026Review
- Conserved Yet Divergent Smc5/6 Complex Degradation by Mammalian Hepatitis B Virus X Proteins.International journal of molecular sciences · 2025Article
- JunB-HBZ nuclear translocation by TGF-β is a key driver in HTLV-1-mediated leukemogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Pre- and Post-Transcriptional Control of HBV Gene Expression: The Road Traveled towards the New Paradigm of HBx, Its Isoforms, and Their Diverse Functions.Biomedicines · 2023Review
- Relevance of HBx for Hepatitis B Virus-Associated Pathogenesis.International journal of molecular sciences · 2023Review
- Dual-Role of Cholesterol-25-Hydroxylase in Regulating Hepatitis B Virus Infection and Replication.mBio · 2022Article
- Canonical and Divergent N-Terminal HBx Isoform Proteins Unveiled: Characteristics and Roles during HBV Replication.Biomedicines · 2021Article
- Molecular pathways in viral hepatitis-associated liver carcinogenesis: An update.World journal of clinical cases · 2021Review
- Phosphorylation of Phylogenetically Conserved Amino Acid Residues Confines HBx within Different Cell Compartments of Human Hepatocarcinoma Cells.Molecules (Basel, Switzerland) · 2021Article
- The Role of IGF/IGF-1R Signaling in Hepatocellular Carcinomas: Stemness-Related Properties and Drug Resistance.International journal of molecular sciences · 2021Review
- Cytochrome P450 1A2 overcomes nuclear factor kappa B-mediated sorafenib resistance in hepatocellular carcinoma.Oncogene · 2021Article
- Spatiotemporal Analysis of Hepatitis B Virus X Protein in Primary Human Hepatocytes.Journal of virology · 2019Article
- Hepatitis B e Antigen Inhibits NF-κB Activity by Interrupting K63-Linked Ubiquitination of NEMO.Journal of virology · 2019Article
- HBx-induced MiR-1269b in NF-κB dependent manner upregulates cell division cycle 40 homolog (CDC40) to promote proliferation and migration in hepatoma cells.Journal of translational medicine · 2016Article
- Small ubiquitin-related modifier 2/3 interacts with p65 and stabilizes it in the cytoplasm in HBV-associated hepatocellular carcinoma.BMC cancer · 2015Article
- Clinical relevance of hepatitis B virus variants.World journal of hepatology · 2015Review
- Hepatitis D and hepatocellular carcinoma.World journal of hepatology · 2015Review
- Effects of antiviral therapy on preventing liver tumorigenesis and hepatocellular carcinoma recurrence.World journal of gastroenterology · 2013Review
- HBV induced HCC: major risk factors from genetic to molecular level.BioMed research international · 2013Review
- Epigenetic repression of E-cadherin expression by hepatitis B virus x antigen in liver cancer.Oncogene · 2012Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The X protein of hepatitis B virus (HBV) is a transcriptional activator which is required for infection and may play an important role in HBV-associated hepatocarcinogenesis. It has been suggested that X acts as a nuclear coactivator or stimulates several signal transduction pathways by acting in the cytoplasm. One of these pathways leads to the nuclear translocation of NF-kappaB. A recent report indicates that X activates NF-kappaB by acting on two cytoplasmic inhibitors of this family of transcription factors: IkappaBalpha and the precursor/inhibitor p105. We demonstrate here that X directly interacts with IkappaBalpha, which is able to transport it to the nucleus by a piggyback mechanism. This transport requires a region of IkappaBalpha (the second ankyrin repeat) which has been demonstrated to be involved in its nuclear import following NF-kappaB activation. Using deletion mutants, we showed that amino acids 249 to 253 of IkappaBalpha (located in the C-terminal part of the sixth ankyrin repeat) play a critical role in the interaction with X. This small region overlaps one of the domains of IkappaBalpha mediating the interaction with the p50 and p65 subunits of NF-kappaB and is also close to the nuclear export sequence of IkappaBalpha, therefore providing a potential explanation for the nuclear accumulation of IkappaBalpha with X. This association can also be observed upon the induction of endogenous IkappaBalpha by tumor necrosis factor alpha (TNF-alpha) treatment of Chang cells expressing X. In accordance with this observation, band shift analysis indicates that X induces a sustained NF-kappaB activation following TNF-alpha treatment, probably by preventing the reassociation of newly synthesized nuclear IkappaBalpha with DNA-bound NF-kappaB complexes.
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