rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2011-3-18
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pubmed:abstractText |
GEX1A is a microbial product with antitumor activity. HeLa cells cultured with GEX1A accumulated p27(Kip) and its C-terminally truncated form p27*. GEX1A inhibited the pre-mRNA splicing of p27, producing p27* from the unspliced mRNA containing the first intron. p27* lacked the site required for E3 ligase-mediated proteolysis of p27, leading to its accumulation in GEX1A-treated cells. The accumulated p27* was able to bind to and inhibit the cyclin E-Cdk2 complex that causes E3 ligase-mediated degradation of p27, which probably triggers the accumulation of p27. By using a series of photoaffinity-labeling derivatives of GEX1A, we found that GEX1A targeted SAP155 protein, a subunit of SF3b responsible for pre-mRNA splicing. The linker length between the GEX1A pharmacophore and the photoreactive group was critical for detection of the GEX1A-binding protein. GEX1A serves as a novel splicing inhibitor that specifically impairs the SF3b function by binding to SAP155.
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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/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Biological Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase Inhibitor...,
http://linkedlifedata.com/resource/pubmed/chemical/Fatty Alcohols,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Pyrans,
http://linkedlifedata.com/resource/pubmed/chemical/RNA Precursors,
http://linkedlifedata.com/resource/pubmed/chemical/Ribonucleoprotein, U2 Small Nuclear,
http://linkedlifedata.com/resource/pubmed/chemical/SF3B1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/herboxidiene
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
1554-8937
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pubmed:author |
pubmed-author:HasegawaMakotoM,
pubmed-author:HorinouchiSueharuS,
pubmed-author:InoueAyuA,
pubmed-author:KosekiKoichiK,
pubmed-author:KunohTatsukiT,
pubmed-author:KuzuyaKoujiK,
pubmed-author:MinoKoshikiK,
pubmed-author:MiuraTatsuhiroT,
pubmed-author:MizukamiTamioT,
pubmed-author:SasakiRyuzoR,
pubmed-author:Won KiSeS,
pubmed-author:YoshidaMinoruM,
pubmed-author:YoshidaTetsuoT
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pubmed:issnType |
Electronic
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pubmed:day |
18
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pubmed:volume |
6
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
229-33
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:21138297-Antineoplastic Agents,
pubmed-meshheading:21138297-Binding Sites,
pubmed-meshheading:21138297-Biological Agents,
pubmed-meshheading:21138297-Cells, Cultured,
pubmed-meshheading:21138297-Cyclin-Dependent Kinase Inhibitor p27,
pubmed-meshheading:21138297-Fatty Alcohols,
pubmed-meshheading:21138297-HeLa Cells,
pubmed-meshheading:21138297-Humans,
pubmed-meshheading:21138297-Molecular Structure,
pubmed-meshheading:21138297-Phosphoproteins,
pubmed-meshheading:21138297-Pyrans,
pubmed-meshheading:21138297-RNA Precursors,
pubmed-meshheading:21138297-RNA Splicing,
pubmed-meshheading:21138297-Ribonucleoprotein, U2 Small Nuclear,
pubmed-meshheading:21138297-Structure-Activity Relationship
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pubmed:year |
2011
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pubmed:articleTitle |
Identification of SAP155 as the target of GEX1A (Herboxidiene), an antitumor natural product.
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pubmed:affiliation |
Nagahama Institute of Bio-Science and Technology, Nagahama, Shiga, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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