ArticleThe Journal of biological chemistry2008
Hepatitis C virus NS5A protein down-regulates the expression of spindle gene Aspm through PKR-p38 signaling pathway.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 49 citations in OpenAlex.
- The impact of genetics and the environment on cancer risk in Indigenous Australians: a narrative review.The Lancet regional health. Western Pacific · 2025Review
- ASPM promotes hepatocellular carcinoma progression by activating Wnt/β-catenin signaling through antagonizing autophagy-mediated Dvl2 degradation.FEBS open bio · 2021Article
- CCNB2, CDC20, AURKA, TOP2A, MELK, NCAPG, KIF20A, UBE2C, PRC1, and ASPM May Be Potential Therapeutic Targets for Hepatocellular Carcinoma Using Integrated Bioinformatic Analysis.International journal of general medicine · 2021Article
- Genetic Variability in Patients with HCV-Related Hepatocellular Carcinoma.Infection and drug resistance · 2021Article
- Aberrant ASPM expression mediated by transcriptional regulation of FoxM1 promotes the progression of gliomas.Journal of cellular and molecular medicine · 2020Article
- Review
- Integrated Bioinformatic Analysis Identifies Networks and Promising Biomarkers for Hepatitis B Virus-Related Hepatocellular Carcinoma.International journal of genomics · 2020Article
- Hepatitis C Virus NS3 Protein Plays a Dual Role in WRN-Mediated Repair of Nonhomologous End Joining.Journal of virology · 2019Article
- Review
- Hepatitis C Virus core+1/ARF Protein Modulates the Cyclin D1/pRb Pathway and Promotes Carcinogenesis.Journal of virology · 2018Article
- Human Kinase/Phosphatase-Wide RNAi Screening Identified Checkpoint Kinase 2 as a Cellular Factor Facilitating Japanese Encephalitis Virus Infection.Frontiers in cellular and infection microbiology · 2018Article
- Molecular basis of hepatocellular carcinoma induced by hepatitis C virus infection.World journal of hepatology · 2017Review
- Classical swine fever virus NS5A protein changed inflammatory cytokine secretion in porcine alveolar macrophages by inhibiting the NF-κB signaling pathway.Virology journal · 2016Article
- FKBP8 interact with classical swine fever virus NS5A protein and promote virus RNA replication.Virus genes · 2016Article
- eEF1A Interacts with the NS5A Protein and Inhibits the Growth of Classical Swine Fever Virus.Viruses · 2015Article
- Murine norovirus replication induces G0/G1 cell cycle arrest in asynchronously growing cells.Journal of virology · 2015Article
- Pathogenesis and prevention of hepatitis C virus-induced hepatocellular carcinoma.Journal of hepatology · 2014Review
- The role of cirrhosis in the etiology of hepatocellular carcinoma.Journal of gastrointestinal cancer · 2014Review
- Screening of cellular proteins that interact with the classical swine fever virus non-structural protein 5A by yeast two-hybrid analysis.Journal of biosciences · 2014Article
- Elevated cyclin B2 expression in invasive breast carcinoma is associated with unfavorable clinical outcome.BMC cancer · 2013Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatitis C virus often causes persistent infection and hepatocellular carcinoma. Studies have demonstrated the roles of viral nonstructural protein 5A (NS5A) in the induction of chromosome aneuploidy, but the molecular mechanisms are not clear. In this study, hydrodynamics-based in vivo transfection was applied to a mouse system. Mouse hepatocytes that successfully expressed NS5A protein were isolated by laser capture microdissection. Gene expression profiles of the NS5A-expressing hepatocytes were examined by an Affymetrix oligonucleotide microarray system. Aspm (abnormal spindle-like, microcephaly associated), which encodes the mitotic spindle protein ASPM, was identified to be differentially expressed in the absence and the presence of NS5A. The down-regulation of Aspm mRNA and ASPM protein was confirmed by real time polymerase chain reaction and Western blot analysis, respectively, both in mouse model systems and in viral subgenomic replicon and in vitro transfection culturing systems. In addition, cultured cells that constitutively expressed NS5A protein showed G(2)/M cell cycle block and chromosome aneuploidy. Overexpression of ASPM relieved the G(2)/M cell cycle block. Furthermore, NS5A protein repressed the promoter activity of Aspm gene in a dose-dependent manner. The regulatory effect was abolished when amino acid substitutions P2209L, T2214A, and T2217G known to interrupt the NS5A-PKR interaction were introduced into the NS5A protein. This indicates that the down-regulation of Aspm expression is via the PKR-p38 signaling pathway. These results suggest that NS5A protein down-regulates the expression of the mitotic spindle protein ASPM and induces aberrant mitotic cell cycle associated with chromosome instability and hepatocellular carcinoma.
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