Cited 72 times in
Nonstructural 5A protein activates beta-catenin signaling cascades: implication of hepatitis C virus-induced liver pathogenesis.
DC Field | Value | Language |
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dc.contributor.author | 김호근 | - |
dc.date.accessioned | 2015-04-24T17:29:51Z | - |
dc.date.available | 2015-04-24T17:29:51Z | - |
dc.date.issued | 2009 | - |
dc.identifier.issn | 0168-8278 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/105510 | - |
dc.description.abstract | BACKGROUND/AIMS: The nonstructural 5A (NS5A) protein of hepatitis C virus (HCV) has been implicated in HCV-induced liver pathogenesis. Wnt/beta-catenin signaling has also been involved in tumorigenesis. To elucidate the molecular mechanism of HCV pathogenesis, we examined the potential effects of HCV NS5A protein on Wnt/beta-catenin signal transduction cascades. METHODS: The effects of NS5A protein on beta-catenin signaling cascades in hepatic cells were investigated by luciferase reporter gene assay, confocal microscopy, immunoprecipitation assay, and immunoblot analysis. RESULTS: beta-Catenin-mediated transcriptional activity is elevated by NS5A protein, in the context of HCV replication, and by infection of cell culture-produced HCV. NS5A protein directly interacts with endogenous beta-catenin and colocalizes with beta-catenin in the cytoplasm. NS5A protein inactivates glycogen synthase kinase 3beta and increases subsequent accumulation of beta-catenin in HepG2 cells. beta-Catenin was also accumulated in HCV patients' liver tissues. In addition, the accumulation of beta-catenin in HCV replicon cells requires both activation of phosphatidylinositol 3-kinase and inactivation of GSK3beta. CONCLUSIONS: NS5A activates beta-catenin signaling cascades through increasing the stability of beta-catenin. This modulation is accomplished by the protein interplay between viral and cellular signaling transducer. These data suggest that NS5A protein may directly be involved in Wnt/beta-catenin-mediated liver pathogenesis. | - |
dc.description.statementOfResponsibility | open | - |
dc.format.extent | 853~864 | - |
dc.relation.isPartOf | JOURNAL OF HEPATOLOGY | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.subject.MESH | Animals | - |
dc.subject.MESH | Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/metabolism | - |
dc.subject.MESH | COS Cells | - |
dc.subject.MESH | Carcinoma, Hepatocellular/etiology | - |
dc.subject.MESH | Carcinoma, Hepatocellular/metabolism | - |
dc.subject.MESH | Carcinoma, Hepatocellular/virology | - |
dc.subject.MESH | Cell Line | - |
dc.subject.MESH | Cell Nucleus/metabolism | - |
dc.subject.MESH | Cercopithecus aethiops | - |
dc.subject.MESH | Cytosol/metabolism | - |
dc.subject.MESH | Glycogen Synthase Kinase 3/antagonists & inhibitors | - |
dc.subject.MESH | Glycogen Synthase Kinase 3/metabolism | - |
dc.subject.MESH | Glycogen Synthase Kinase 3 beta | - |
dc.subject.MESH | Hepacivirus/genetics | - |
dc.subject.MESH | Hepacivirus/pathogenicity* | - |
dc.subject.MESH | Hepacivirus/physiology* | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | In Vitro Techniques | - |
dc.subject.MESH | Liver Neoplasms/etiology* | - |
dc.subject.MESH | Liver Neoplasms/metabolism | - |
dc.subject.MESH | Liver Neoplasms/virology | - |
dc.subject.MESH | Phosphatidylinositol 3-Kinases/metabolism | - |
dc.subject.MESH | Protein Interaction Domains and Motifs | - |
dc.subject.MESH | Recombinant Proteins/genetics | - |
dc.subject.MESH | Recombinant Proteins/metabolism | - |
dc.subject.MESH | Replicon | - |
dc.subject.MESH | Sequence Deletion | - |
dc.subject.MESH | Signal Transduction | - |
dc.subject.MESH | Transcription Factor 4 | - |
dc.subject.MESH | Transcription Factors/metabolism | - |
dc.subject.MESH | Transfection | - |
dc.subject.MESH | Viral Nonstructural Proteins/genetics | - |
dc.subject.MESH | Viral Nonstructural Proteins/metabolism* | - |
dc.subject.MESH | Virus Replication | - |
dc.subject.MESH | Wnt Proteins/metabolism | - |
dc.subject.MESH | beta Catenin/chemistry | - |
dc.subject.MESH | beta Catenin/genetics | - |
dc.subject.MESH | beta Catenin/metabolism* | - |
dc.title | Nonstructural 5A protein activates beta-catenin signaling cascades: implication of hepatitis C virus-induced liver pathogenesis. | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Pathology (병리학) | - |
dc.contributor.googleauthor | Chul-Yong Park | - |
dc.contributor.googleauthor | Soo-Ho Choi | - |
dc.contributor.googleauthor | Sang-Min Kang | - |
dc.contributor.googleauthor | Ju-Il Kang | - |
dc.contributor.googleauthor | Byung-Yoon Ahn | - |
dc.contributor.googleauthor | Hoguen Kim | - |
dc.contributor.googleauthor | Guhung Jung | - |
dc.contributor.googleauthor | Kang-Yell Choi | - |
dc.contributor.googleauthor | Soon B. Hwang | - |
dc.identifier.doi | 10.1016/j.jhep.2009.06.026 | - |
dc.admin.author | false | - |
dc.admin.mapping | false | - |
dc.contributor.localId | A01183 | - |
dc.relation.journalcode | J01441 | - |
dc.identifier.eissn | 1600-0641 | - |
dc.identifier.pmid | 19726098 | - |
dc.identifier.url | http://www.sciencedirect.com/science/article/pii/S0168827809005273 | - |
dc.subject.keyword | Hepatitis C virus | - |
dc.subject.keyword | Liver pathogenesis | - |
dc.subject.keyword | NS5A protein | - |
dc.subject.keyword | β-Catenin signaling | - |
dc.subject.keyword | Tumorigenesis | - |
dc.contributor.alternativeName | Kim, Ho Keun | - |
dc.contributor.affiliatedAuthor | Kim, Ho Keun | - |
dc.citation.volume | 51 | - |
dc.citation.number | 5 | - |
dc.citation.startPage | 853 | - |
dc.citation.endPage | 864 | - |
dc.identifier.bibliographicCitation | JOURNAL OF HEPATOLOGY, Vol.51(5) : 853-864, 2009 | - |
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