ArticleOncogene2003
Integrity of c-Raf-1/MEK signal transduction cascade is essential for hepatitis B virus gene expression.
Article in Oncogene, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- Sorafenib for treatment of hepatocellular carcinoma: a systematic review.Digestive diseases and sciences · 2012Pooled it
- The Malignant Transformation of Viral Hepatitis to Hepatocellular Carcinoma: Mechanisms and Interventions.MedComm · 2025Review
- The mechanism of TiaoGanYiPi formula for treating chronic hepatitis B by network pharmacology and molecular docking verification.Scientific reports · 2021Article
- Effect of Hepatitis Viruses on the Nrf2/Keap1-Signaling Pathway and Its Impact on Viral Replication and Pathogenesis.International journal of molecular sciences · 2019Review
- HBV infection increases the risk of macular degeneration: the roles of HBx-mediated sensitization of retinal pigment epithelial cells to UV and blue light irradiation.Journal of translational medicine · 2018Article
- Evolving role of Sorafenib in the management of hepatocellular carcinoma.World journal of clinical oncology · 2017Review
- Detection of Hepatitis B Virus Large Surface Protein Using a Time-Resolved Immunofluorometric Assay.Journal of clinical laboratory analysis · 2015Article
- Molecular targeting agents associated with transarterial chemoembolization or radiofrequency ablation in hepatocarcinoma treatment.World journal of gastroenterology · 2014Review
- Identification and characterization of a novel bipartite nuclear localization signal in the hepatitis B virus polymerase.World journal of gastroenterology · 2013Article
- HBx induces HepG-2 cells autophagy through PI3K/Akt-mTOR pathway.Molecular and cellular biochemistry · 2013Article
- The MAPK MEK1/2-ERK1/2 Pathway and Its Implication in Hepatocyte Cell Cycle Control.International journal of hepatology · 2012Article
- Article
- Hepatitis B virus induces expression of antioxidant response element-regulated genes by activation of Nrf2.The Journal of biological chemistry · 2010Article
- The role of signaling pathways in the development and treatment of hepatocellular carcinoma.Oncogene · 2010Review
- HBV life cycle: entry and morphogenesis.Viruses · 2009Article
- Hepatitis B virus-induced oncogenesis.World journal of gastroenterology · 2007Review
- Study of transactivating effect of pre-S2 protein of hepatitis B virus and cloning of genes transactivated by pre-S2 protein with suppression subtractive hybridization.World journal of gastroenterology · 2005Article
- Signal transduction pathways that inhibit hepatitis B virus replication.Proceedings of the National Academy of Sciences of the United States of America · 2004Article
- Reconstitution of gene expression from a regulatory-protein-deficient hepatitis B virus genome by cell-permeable HBx protein.EMBO reports · 2003Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The genome of hepatitis B virus (HBV) encodes two transcriptional activators: the HBx protein and the PreS2-activator large surface protein (LHBs). Both proteins trigger activation of c-Raf-1/MEK kinase cascade. In case of HBx this can be mediated by a PKC-independent and Ras-dependent mechanism, in case of LHBs activation is PKC-dependent and does not require Ras. Selective destruction of either LHBs- or of HBx-specific activation does not result in significant decrease of viral production from transfected HepG2 cells. Simultaneous inhibition of LHBs- and HBx-dependent activation by blocking signaling steps common to both activators, using trans dominant negative c-Raf-1- or MEK-specific inhibitors, abolished HBV gene expression. In accordance with this no HBV propagation was observed after transfection of a mutated HBV genome defective for HBx- and PreS2-activator function. A detailed analysis revealed that the observed inhibition of HBV- propagation is because of a significant reduction of HBV-specific RNA resulting in an inhibition of the de novo synthesis of viral compounds (viral proteins and nucleic acid) and not by blocking secretion or assembly of the virus. Based on these results we conclude that transcriptional-activator function, mediated by the c-Raf-1/MEK signaling cascade, is essential for HBV gene expression.
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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.