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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
23
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pubmed:dateCreated |
2003-12-17
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pubmed:abstractText |
EWS/ETS is a chimeric protein identified in most Ewing's sarcomas. Although EWS/ETS has been shown to activate transcription as a transcription factor, the detailed targets of EWS/ETS in transformed cells have not been clarified. Herein, we demonstrate that telomerase is a new target of EWS/ETS fusions. Both telomerase activity and the expression level of telomerase reverse transcriptase (TERT) mRNA were up-regulated in NIH3T3 cells transformed by EWS/E1AF and EWS/FLI1 as well as in two Ewing's sarcoma cell lines. Luciferase assay using the TERT promoter revealed that EWS/E1AF and EWS/FLI1 function as positive regulators of TERT transcription in an ETS binding site-independent manner. EWS/ETS appeared to be included in the initiation complex of TERT transcription and to cooperate with CREB-binding protein (CBP)/p300. When EWS/FLI1 was knocked down in Ewing's sarcomas cells by RNA interference, the expression level of TERT mRNA and the telomerase activity were significantly decreased. These findings indicate that EWS/ETS fusion proteins activate human telomerase activity in Ewing's tumors through up-regulation of TERT gene expression, probably as a transcriptional coactivator.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adenovirus E1A Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/ETV4 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/EWS-FLI fusion protein,
http://linkedlifedata.com/resource/pubmed/chemical/Oncogene Proteins, Fusion,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Protein c-fli-1,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-ets,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/RNA-Binding Protein EWS,
http://linkedlifedata.com/resource/pubmed/chemical/TERT protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Telomerase,
http://linkedlifedata.com/resource/pubmed/chemical/Tert protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0008-5472
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pubmed:author |
pubmed-author:AoyagiMarikoM,
pubmed-author:ArigaHiroyoshiH,
pubmed-author:HattaMitsutokiM,
pubmed-author:HigashinoFumihiroF,
pubmed-author:ItohMiyukiM,
pubmed-author:KobayashiMasanobuM,
pubmed-author:KohgoTakaoT,
pubmed-author:KyoSatoruS,
pubmed-author:NakajimaKohichiK,
pubmed-author:OhnoTakatoshiT,
pubmed-author:SanoHidehikoH,
pubmed-author:ShindohMasanobuM,
pubmed-author:TairaTakahiroT,
pubmed-author:TakahashiAkikoA,
pubmed-author:YoshidaKoichiK
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
63
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
8338-44
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:14678994-Adenovirus E1A Proteins,
pubmed-meshheading:14678994-Animals,
pubmed-meshheading:14678994-Cell Line, Tumor,
pubmed-meshheading:14678994-DNA-Binding Proteins,
pubmed-meshheading:14678994-Enzyme Activation,
pubmed-meshheading:14678994-HeLa Cells,
pubmed-meshheading:14678994-Humans,
pubmed-meshheading:14678994-Mice,
pubmed-meshheading:14678994-NIH 3T3 Cells,
pubmed-meshheading:14678994-Oncogene Proteins, Fusion,
pubmed-meshheading:14678994-Promoter Regions, Genetic,
pubmed-meshheading:14678994-Proto-Oncogene Protein c-fli-1,
pubmed-meshheading:14678994-Proto-Oncogene Proteins,
pubmed-meshheading:14678994-Proto-Oncogene Proteins c-ets,
pubmed-meshheading:14678994-RNA, Messenger,
pubmed-meshheading:14678994-RNA Interference,
pubmed-meshheading:14678994-RNA-Binding Protein EWS,
pubmed-meshheading:14678994-Sarcoma, Ewing,
pubmed-meshheading:14678994-Telomerase,
pubmed-meshheading:14678994-Transcription Factors,
pubmed-meshheading:14678994-Transcriptional Activation
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pubmed:year |
2003
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pubmed:articleTitle |
EWS/ETS fusions activate telomerase in Ewing's tumors.
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pubmed:affiliation |
Department of Oral Pathobiological Science, Hokkaido University Graduate School of Dental Medicine, Sapporo, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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