Linked Life Data

17065236

Source:http://linkedlifedata.com/resource/pubmed/id/17065236

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2006-12-22
pubmed:abstractText
Multidrug resistance-associated protein 2 (Mrp2/Abcc2), an organic anion transporter present in the apical membrane of hepatocytes, renal epithelial cells, and enterocytes, is postulated to undergo translational regulation. Transcription of rat hepatic Mrp2 mRNA is initiated at multiple sites (-213, -163, -132, and -98 nucleotides relative to the Mrp2 ATG) and contains potential upstream open reading frames (uORFs) in the 5' untranslated region (UTR) starting at -213, -149 and -109 nucleotides. Ribonuclease protection assays demonstrated that transcription of the Mrp2 gene at the various initiation sites was tissue-specific, with the major initiation site in the liver and kidney being -98 and -132 nucleotides, respectively. In the jejunum, the primary and secondary initiation sites were -98 and -132 nucleotides, respectively, with the converse true in the ileum. The relative abundance of these Mrp2 transcripts expressed in tissues varied with age from birth to the adult. HepG2 transient expression assays and in vitro translation assays in which the 5'UTRs were fused with a luciferase reporter showed that the 5'UTR without any uORF (-98 nucleotide) expressed maximal luciferase activity compared with those with one (-132 nucleotides), two (-163 nucleotides), or three (-213 nucleotides) uORFs. Disruption of the uORF by site-directed mutagenesis at nucleotide -109 enhanced luciferase activity 2- to 3-fold, whereas disruption of the uORF at nucleotide -149 had little effect. We conclude that among the uORFs in the Mrp2 5'UTR, the uORF starting at nucleotide -109 probably plays an important role in the regulation of Mrp2 protein expression.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0026-895X
pubmed:author
pubmed:issnType
Print
pubmed:volume
71
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
377-83
pubmed:dateRevised
2007-12-3
pubmed:meshHeading
pubmed-meshheading:17065236-5' Untranslated Regions, pubmed-meshheading:17065236-ATP-Binding Cassette Transporters, pubmed-meshheading:17065236-Animals, pubmed-meshheading:17065236-Base Sequence, pubmed-meshheading:17065236-Carcinoma, Hepatocellular, pubmed-meshheading:17065236-Cell Line, Tumor, pubmed-meshheading:17065236-DNA, Complementary, pubmed-meshheading:17065236-DNA Primers, pubmed-meshheading:17065236-Humans, pubmed-meshheading:17065236-Liver Neoplasms, pubmed-meshheading:17065236-Molecular Sequence Data, pubmed-meshheading:17065236-Open Reading Frames, pubmed-meshheading:17065236-Polymerase Chain Reaction, pubmed-meshheading:17065236-RNA, Messenger, pubmed-meshheading:17065236-Rats, pubmed-meshheading:17065236-Transcription, Genetic, pubmed-meshheading:17065236-Uridine Triphosphate
pubmed:year
2007
pubmed:articleTitle
Translational regulation of rat multidrug resistance-associated protein 2 expression is mediated by upstream open reading frames in the 5' untranslated region.
pubmed:affiliation
Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40536-0305, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural