Source:http://linkedlifedata.com/resource/pubmed/id/15047715
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
22
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pubmed:dateCreated |
2004-5-24
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pubmed:abstractText |
The POU transcription factor Oct-4 is a master regulator affecting the fate of pluripotent embryonic stem cells. However, the precise mechanisms by which the activation and expression of Oct-4 are regulated still remain to be elucidated. We describe here a novel murine ubiquitin ligase, Wwp2, that specifically interacts with Oct-4 and promotes its ubiquitination both in vivo and in vitro. Remarkably, the expression of a catalytically inactive point mutant of Wwp2 abolishes Oct-4 ubiquitination. Moreover, Wwp2 promotes Oct-4 degradation in the presence of overexpressed ubiquitin. The degradation is blocked by treatment with proteasome inhibitor. Fusion of a single ubiquitin to Oct-4 inactivates its transcriptional activity in a heterologous Oct-4-driven reporter system. Furthermore, overexpression of Wwp2 in embryonic stem cells significantly reduces the Oct-4-transcriptional activities. Collectively, we demonstrate for the first time that Oct-4 can be post-translationally modified by ubiquitination and that this modification dramatically suppresses its transcriptional activity. These results reveal that the functional status of Oct-4, in addition to its expression level, dictates its transcriptional activity, and the results open up a new avenue to understand how Oct-4 defines the fate of embryonic stem cells.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Octamer Transcription Factor-3,
http://linkedlifedata.com/resource/pubmed/chemical/Pou5f1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin-Protein Ligases,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitins
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
28
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pubmed:volume |
279
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
23495-503
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:15047715-Animals,
pubmed-meshheading:15047715-Cell Differentiation,
pubmed-meshheading:15047715-DNA-Binding Proteins,
pubmed-meshheading:15047715-Mice,
pubmed-meshheading:15047715-Octamer Transcription Factor-3,
pubmed-meshheading:15047715-Protein Binding,
pubmed-meshheading:15047715-Signal Transduction,
pubmed-meshheading:15047715-Stem Cells,
pubmed-meshheading:15047715-Transcription Factors,
pubmed-meshheading:15047715-Ubiquitin-Protein Ligases,
pubmed-meshheading:15047715-Ubiquitins
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pubmed:year |
2004
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pubmed:articleTitle |
Wwp2, an E3 ubiquitin ligase that targets transcription factor Oct-4 for ubiquitination.
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pubmed:affiliation |
Developmental Biology Department, Health Science Center, Shanghai Second Medical University and Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 411 He Fei Road, Shanghai 200025, China.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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