ArticleThe EMBO journal2002
The PreS2 activator MHBs(t) of hepatitis B virus activates c-raf-1/Erk2 signaling in transgenic mice.
Article in The EMBO journal, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed.
- New Insights into the Role of NF-κB in Hepatitis B Virus Infection.International journal of biological sciences · 2026Review
- Hepatitis B virus integration and hepatocarcinogenesis.Liver research (Beijing, China) · 2025Review
- Surface Gene Mutations of Hepatitis B Virus and Related Pathogenic Mechanisms: A Narrative Review.Viruses · 2025Review
- Hepatitis B surface antigen: carcinogenesis mechanisms and clinical implications in hepatocellular carcinoma.Experimental hematology & oncology · 2025Review
- Efficacy Analysis of TACE Combined with Lenvatinib and PD-1 Inhibitors in the Treatment of Hepatitis B Virus-Related Unresectable Hepatocellular Carcinoma.Journal of hepatocellular carcinoma · 2025Article
- The impact of HBx protein on mitochondrial dynamics and associated signaling pathways strongly depends on the hepatitis B virus genotype.Journal of virology · 2024Article
- Hepatitis B Surface Antigen Isoforms: Their Clinical Implications, Utilisation in Diagnosis, Prevention and New Antiviral Strategies.Pathogens (Basel, Switzerland) · 2024Review
- Relevance of HBx for Hepatitis B Virus-Associated Pathogenesis.International journal of molecular sciences · 2023Review
- Review
- Phosphoproteomics Unravel HBV Triggered Rewiring of Host Phosphosignaling Events.International journal of molecular sciences · 2022Article
- [Hepatitis B and C: mechanisms of virus-induced liver pathogenesis and tumorigenesis].Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz · 2022Review
- Hepatitis B virus middle surface antigen loss promotes clinical variant persistence in mouse models.Virulence · 2021Article
- Molecular Mechanisms and Animal Models of HBV-Related Hepatocellular Carcinoma: With Emphasis on Metastatic Tumor Antigen 1.International journal of molecular sciences · 2021Review
- Hepatitis B Virus DNA Integration and Clonal Expansion of Hepatocytes in the Chronically Infected Liver.Viruses · 2021Review
- DNA damage in cancer development: special implications in viral oncogenesis.American journal of cancer research · 2021Article
- Viral Biomarkers for Hepatitis B Virus-Related Hepatocellular Carcinoma Occurrence and Recurrence.Frontiers in microbiology · 2021Review
- Paradoxical HBsAg and anti-HBs coexistence among Chronic HBV Infections: Causes and Consequences.International journal of biological sciences · 2021Review
- Intracellular Trafficking of HBV Particles.Cells · 2020Review
- Effect of Hepatitis Viruses on the Nrf2/Keap1-Signaling Pathway and Its Impact on Viral Replication and Pathogenesis.International journal of molecular sciences · 2019Review
- Human DNA Virus Exploitation of the MAPK-ERK Cascade.International journal of molecular sciences · 2019Review
4 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The large hepatitis B virus (HBV) surface protein (LHBs) and C-terminally truncated middle size surface proteins (MHBs(t)) form the family of the PreS2 activator proteins of HBV. Their transcriptional activator function is based on the cytoplasmic orientation of the PreS2 domain. MHBs(t) activators are paradigmatic for this class of activators. Here we report that MHBs(t) is protein kinase C (PKC)-dependently phosphorylated at Ser28. The integrity of the phosphorylation site is essential for the activator function. MHBs(t) triggers PKC-dependent activation of c-Raf-1/Erk2 signaling that is a prerequisite for MHBs(t)-dependent activation of AP-1 and NF-kappaB. To analyze the pathophysiological relevance of these data in vivo, transgenic mice were established that produce the PreS2 activator MHBs(t) specifically in the liver. In these mice, a permanent PreS2-dependent specific activation of c-Raf-1/Erk2 signaling was observed, resulting in an increased hepatocyte proliferation rate. In transgenics older than 15 months, an increased incidence of liver tumors occurs. These data suggest that PreS2 activators LHBs and MHBs(t) exert a tumor promoter-like function by activation of key enzymes of proliferation control.
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