DC Field | Value | Language |
---|---|---|
dc.contributor.author | Lee, Jungwoon | ko |
dc.contributor.author | Kim, Ja Young | ko |
dc.contributor.author | Kang, In Young | ko |
dc.contributor.author | Kim, Hye Kyoung | ko |
dc.contributor.author | Han, Yong Mahn | ko |
dc.contributor.author | Kim, Jungho | ko |
dc.date.accessioned | 2013-03-07T14:50:02Z | - |
dc.date.available | 2013-03-07T14:50:02Z | - |
dc.date.created | 2012-02-06 | - |
dc.date.created | 2012-02-06 | - |
dc.date.issued | 2007-09 | - |
dc.identifier.citation | BIOCHEMICAL JOURNAL, v.406, no.3, pp.519 - 526 | - |
dc.identifier.issn | 0264-6021 | - |
dc.identifier.uri | http://hdl.handle.net/10203/90430 | - |
dc.description.abstract | The t(6;22)(p21;q12) translocation associated with human bone and soft-tissue tumours results in a chimaeric molecule fusing the NTD (N-terminal domain) of the EWS (Ewing's sarcoma) gene to the CTD (C-terminal domain) of the Oct-4 (octamer-4) embryonic gene. Since the N-terminal domains of EWS and Oct-4 are structurally different, in the present study we have assessed the functional consequences of the EWS-Oct-4 fusion. We find that this chimaeric gene encodes a nuclear protein which binds DNA with the same sequence specificity as the parental Oct-4 protein. Comparison of the transactivation properties of EWS-Oct-4 and Oct-4 indicates that the former has higher transactivation activity for a known target reporter gene containing Oct-4 binding. Deletion analysis of the functional domains of EWS-Oct-4 indicates that the EWS (NTD), the POU domain and the CTD of EWS-Oct-4 are necessary for full transactivation potential. EWS-Oct-4 induced the expression of fgf-4 (fibroblast growth factor 4) and nanog, which are potent mitogens as well as Oct-4 downstream target genes whose promoters contain potential Oct-4-binding sites. Finally, ectopic expression of EWS-Oct-4 in Oct-4-null ZHBTc4 ES (embryonic stem) cells resulted in increased tumorigenic growth potential in nude mice. These results suggest that the oncogenic effect of the t(6;22) translocation is due to the EWS-Oct-4 chimaeric protein and that fusion of the EWS NTD to the Oct-4 DNA-binding domain produces a transforming chimaeric product. | - |
dc.language | English | - |
dc.publisher | PORTLAND PRESS LTD | - |
dc.subject | GERM-CELL TUMORS | - |
dc.subject | HUMAN CHORIONIC-GONADOTROPIN | - |
dc.subject | TRANSCRIPTION FACTOR OCT-3/4 | - |
dc.subject | DNA-BINDING DOMAIN | - |
dc.subject | TERMINAL DOMAIN | - |
dc.subject | SELF-RENEWAL | - |
dc.subject | STEM-CELLS | - |
dc.subject | POU-DOMAIN | - |
dc.subject | EXPRESSION | - |
dc.subject | DIFFERENTIATION | - |
dc.title | The EWS-Oct-4 fusion gene encodes a transforming gene | - |
dc.type | Article | - |
dc.identifier.wosid | 000249537700016 | - |
dc.identifier.scopusid | 2-s2.0-34548720314 | - |
dc.type.rims | ART | - |
dc.citation.volume | 406 | - |
dc.citation.issue | 3 | - |
dc.citation.beginningpage | 519 | - |
dc.citation.endingpage | 526 | - |
dc.citation.publicationname | BIOCHEMICAL JOURNAL | - |
dc.identifier.doi | 10.1042/BJ20070243 | - |
dc.contributor.localauthor | Han, Yong Mahn | - |
dc.contributor.nonIdAuthor | Lee, Jungwoon | - |
dc.contributor.nonIdAuthor | Kim, Ja Young | - |
dc.contributor.nonIdAuthor | Kang, In Young | - |
dc.contributor.nonIdAuthor | Kim, Hye Kyoung | - |
dc.contributor.nonIdAuthor | Kim, Jungho | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordAuthor | bone and soft-tissue tumour | - |
dc.subject.keywordAuthor | chromosomal translocation | - |
dc.subject.keywordAuthor | EWS-Oct-4 fusion protein | - |
dc.subject.keywordAuthor | transactivation | - |
dc.subject.keywordAuthor | transformation | - |
dc.subject.keywordPlus | GERM-CELL TUMORS | - |
dc.subject.keywordPlus | HUMAN CHORIONIC-GONADOTROPIN | - |
dc.subject.keywordPlus | TRANSCRIPTION FACTOR OCT-3/4 | - |
dc.subject.keywordPlus | DNA-BINDING DOMAIN | - |
dc.subject.keywordPlus | TERMINAL DOMAIN | - |
dc.subject.keywordPlus | SELF-RENEWAL | - |
dc.subject.keywordPlus | STEM-CELLS | - |
dc.subject.keywordPlus | POU-DOMAIN | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordPlus | DIFFERENTIATION | - |
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