Hepatitis B virus X protein enhances transcriptional activity of hypoxia-inducible factor-1 alpha through activation of mitogen-activated protein kinase pathway
DC Field | Value | Language |
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dc.contributor.author | Yoo, YG | - |
dc.contributor.author | Oh, SH | - |
dc.contributor.author | Park, ES | - |
dc.contributor.author | Cho, H | - |
dc.contributor.author | Lee, N | - |
dc.contributor.author | Park, H | - |
dc.contributor.author | Kim, DK | - |
dc.contributor.author | Yu, DY | - |
dc.contributor.author | Seong, JK | - |
dc.contributor.author | Lee, MO | - |
dc.date.available | 2019-05-30T08:40:01Z | - |
dc.date.issued | 2003-10-03 | - |
dc.identifier.issn | 0021-9258 | - |
dc.identifier.issn | 1083-351X | - |
dc.identifier.uri | https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/24933 | - |
dc.description.abstract | Hepatitis B virus X protein (HBx) of the hepatitis B virus was strongly implicated in angiogenesis and metastasis during hepatocarcinogenesis. Here, we explored the possibility of cross-talk between HBx and hypoxia-inducible factor-1alpha (HIF-1alpha), a potent transcriptional inducer of angiogenic factors. First, we showed that stability of HIF-1alpha protein was increased by HBx in HBx-inducible Chang liver cells as well as in transient HBx expression system of non-hepatic cells. Immunofluorescence studies revealed that the HBx-induced HIF-1alpha was partially translocated into the nucleus in majority of cells while additional CoCl2-induced hypoxic condition caused complete nuclear translocation. Second, HBx induced both phosphorylation of HIF-1alpha and activation of p42/p44 mitogen-activated protein kinases (MAPKs), which were synergistically enhanced in the presence of CoCl2. Furthermore, HBx enhanced transcriptional activity of HIF-1alpha in the reporter genes encoding hypoxia response element or VEGF promoter. Either treatment of MEK inhibitor PD98059 or coexpression of dominant-negative MAPK mutants abolished the HBx-induced transcriptional activity and protein stability as well as nuclear translocation of HIF-1alpha, suggesting that HBx activates HIF-1alpha through MAPK pathway. Third, the association of HIF-1alpha with von Hippel-Lindau was decreased but the association with CREB-binding protein was enhanced in the presence of HBx, suggesting the molecular mechanism by which HBx enhances the protein stability and transactivation function of HIF-1alpha. Finally, we demonstrated that expression of HIF-1alpha and vascular endothelial growth factor was increased in the liver of HBx-transgenic mice, suggesting that the cross-talk between HIF-1alpha and HBx may lead to transcriptional activation of HIF-1alpha target genes, which play a critical role in hepatocarcinogenesis. | - |
dc.format.extent | 9 | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC | - |
dc.title | Hepatitis B virus X protein enhances transcriptional activity of hypoxia-inducible factor-1 alpha through activation of mitogen-activated protein kinase pathway | - |
dc.type | Article | - |
dc.identifier.doi | 10.1074/jbc.M305101200 | - |
dc.identifier.bibliographicCitation | JOURNAL OF BIOLOGICAL CHEMISTRY, v.278, no.40, pp 39076 - 39084 | - |
dc.description.isOpenAccess | N | - |
dc.identifier.wosid | 000185575100121 | - |
dc.identifier.scopusid | 2-s2.0-0141532010 | - |
dc.citation.endPage | 39084 | - |
dc.citation.number | 40 | - |
dc.citation.startPage | 39076 | - |
dc.citation.title | JOURNAL OF BIOLOGICAL CHEMISTRY | - |
dc.citation.volume | 278 | - |
dc.type.docType | Article | - |
dc.publisher.location | 미국 | - |
dc.subject.keywordPlus | ENDOTHELIAL GROWTH-FACTOR | - |
dc.subject.keywordPlus | TRANSCATHETER ARTERIAL EMBOLIZATION | - |
dc.subject.keywordPlus | UBIQUITIN-PROTEASOME PATHWAY | - |
dc.subject.keywordPlus | TUMOR-SUPPRESSOR PROTEIN | - |
dc.subject.keywordPlus | FACTOR 1-ALPHA | - |
dc.subject.keywordPlus | HEPATOCELLULAR-CARCINOMA | - |
dc.subject.keywordPlus | HBX PROTEIN | - |
dc.subject.keywordPlus | FACTOR GENE | - |
dc.subject.keywordPlus | SIGNAL-TRANSDUCTION | - |
dc.subject.keywordPlus | INDUCED EXPRESSION | - |
dc.relation.journalResearchArea | Biochemistry & Molecular Biology | - |
dc.relation.journalWebOfScienceCategory | Biochemistry & Molecular Biology | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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