Source:http://linkedlifedata.com/resource/pubmed/id/15750632
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
22
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pubmed:dateCreated |
2005-6-14
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pubmed:abstractText |
Vaults have been suggested to play a direct role in multidrug resistance (MDR) to anticancer drugs. The human major vault protein (MVP) also known as lung resistance-related protein (LRP) represents the predominant component of vaults that may be involved in the defense against xenobiotics. Here, we demonstrate that besides MDR-related cytostatics, also the non-MDR-related drug 5-fluorouracil (5-FU) was able to induce MVP mRNA and protein expression. Treatment with 5-FU amplified the binding activity and interaction of the transcription factor Y-box binding protein-1 (YB-1) with the Y-box of the human MVP gene promoter in a time-dependent manner. 5-FU also induced reporter expressions driven by a panel of newly generated MVP promoter deletion mutants. Interestingly, stably YB-1 overexpressing cell clones showed enhanced binding of YB-1 to the Y-box motif, associated with enhanced basal as well as 5-FU-inducible MVP promoter-driven reporter expressions. Moreover, transduction of YB-1 cDNA led to increased expression of endogenous MVP protein. Under physiological conditions, we observed a strong coexpression of MVP and YB-1 in human colon carcinoma specimen. In summary, our data demonstrate a direct involvement of YB-1 in controlling basal and 5-FU-induced MVP promoter activity. Therefore, YB-1 is directly linked to MVP-mediated drug resistance.
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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/Antimetabolites, Antineoplastic,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Fluorouracil,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Vault Ribonucleoprotein Particles,
http://linkedlifedata.com/resource/pubmed/chemical/Y-Box-Binding Protein 1,
http://linkedlifedata.com/resource/pubmed/chemical/YBX1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/major vault protein
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0950-9232
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
19
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pubmed:volume |
24
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3606-18
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:15750632-Antimetabolites, Antineoplastic,
pubmed-meshheading:15750632-Colonic Neoplasms,
pubmed-meshheading:15750632-DNA-Binding Proteins,
pubmed-meshheading:15750632-Drug Resistance, Multiple,
pubmed-meshheading:15750632-Drug Resistance, Neoplasm,
pubmed-meshheading:15750632-Electrophoretic Mobility Shift Assay,
pubmed-meshheading:15750632-Enzyme-Linked Immunosorbent Assay,
pubmed-meshheading:15750632-Flow Cytometry,
pubmed-meshheading:15750632-Fluorouracil,
pubmed-meshheading:15750632-Humans,
pubmed-meshheading:15750632-Immunohistochemistry,
pubmed-meshheading:15750632-Nuclear Proteins,
pubmed-meshheading:15750632-Promoter Regions, Genetic,
pubmed-meshheading:15750632-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:15750632-Vault Ribonucleoprotein Particles,
pubmed-meshheading:15750632-Y-Box-Binding Protein 1
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pubmed:year |
2005
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pubmed:articleTitle |
YB-1 facilitates basal and 5-fluorouracil-inducible expression of the human major vault protein (MVP) gene.
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pubmed:affiliation |
Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Strasse 10, 13092 Berlin, Germany. ustein@mdc-berlin.de
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pubmed:publicationType |
Journal Article
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