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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
22
pubmed:dateCreated
2005-6-14
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0950-9232
pubmed:author
pubmed:issnType
Print
pubmed:day
19
pubmed:volume
24
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3606-18
pubmed:dateRevised
2011-11-17
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
pubmed:year
2005
pubmed:articleTitle
YB-1 facilitates basal and 5-fluorouracil-inducible expression of the human major vault protein (MVP) gene.
pubmed:affiliation
Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Strasse 10, 13092 Berlin, Germany. ustein@mdc-berlin.de
pubmed:publicationType
Journal Article