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rdf:type |
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lifeskim:mentions |
umls-concept:C0015879,
umls-concept:C0027950,
umls-concept:C0035696,
umls-concept:C0040711,
umls-concept:C0086222,
umls-concept:C0086418,
umls-concept:C0179400,
umls-concept:C0205147,
umls-concept:C0205178,
umls-concept:C0242210,
umls-concept:C0439539,
umls-concept:C1145667,
umls-concept:C1705733,
umls-concept:C1710548
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pubmed:issue |
34
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pubmed:dateCreated |
2005-8-22
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pubmed:abstractText |
Intracellular levels of the light (L) and heavy (H) ferritin subunits are regulated by iron at the level of message translation via a modulated interaction between the iron regulatory proteins (IRP1 and IRP2) and a 5'-untranslated region. Iron-responsive element (IRE). Here we show that iron and interleukin-1beta (IL-1beta) act synergistically to increase H- and L-ferritin expression in hepatoma cells. A GC-rich cis-element, the acute box (AB), located downstream of the IRE in the H-ferritin mRNA 5'-untranslated region, conferred a substantial increase in basal and IL-1beta-stimulated translation over a similar time course to the induction of endogenous ferritin. A scrambled version of the AB was unresponsive to IL-1. Targeted mutation of the AB altered translation; reverse orientation and a deletion of the AB abolished the wild-type stem-loop structure and abrogated translational enhancement, whereas a conservative structural mutant had little effect. Labeled AB transcripts formed specific complexes with hepatoma cell extracts that contained the poly(C)-binding proteins, iso-alphaCP1 and -alphaCP2, which have well defined roles as translation regulators. Iron influx increased the association of alphaCP1 with ferritin mRNA and decreased the alphaCP2-ferritin mRNA interaction, whereas IL-1beta reduced the association of alphaCP1 and alphaCP2 with H-ferritin mRNA. In summary, the H-ferritin mRNA AB is a key cis-acting translation enhancer that augments H-subunit expression in Hep3B and HepG2 hepatoma cells, in concert with the IRE. The regulated association of H-ferritin mRNA with the poly(C)-binding proteins suggests a novel role for these proteins in ferritin translation and iron homeostasis in human liver.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/5' Untranslated Regions,
http://linkedlifedata.com/resource/pubmed/chemical/Chloramphenicol O-Acetyltransferase,
http://linkedlifedata.com/resource/pubmed/chemical/FTH1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Ferritins,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-1,
http://linkedlifedata.com/resource/pubmed/chemical/Iron,
http://linkedlifedata.com/resource/pubmed/chemical/Luciferases,
http://linkedlifedata.com/resource/pubmed/chemical/Poly C,
http://linkedlifedata.com/resource/pubmed/chemical/Pregnancy Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
26
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pubmed:volume |
280
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
30032-45
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:15967798-5' Untranslated Regions,
pubmed-meshheading:15967798-Base Sequence,
pubmed-meshheading:15967798-Carcinoma, Hepatocellular,
pubmed-meshheading:15967798-Cell Line, Tumor,
pubmed-meshheading:15967798-Chloramphenicol O-Acetyltransferase,
pubmed-meshheading:15967798-Cytoplasm,
pubmed-meshheading:15967798-Dose-Response Relationship, Drug,
pubmed-meshheading:15967798-Enhancer Elements, Genetic,
pubmed-meshheading:15967798-Ferritins,
pubmed-meshheading:15967798-Genes, Reporter,
pubmed-meshheading:15967798-Humans,
pubmed-meshheading:15967798-Immunoblotting,
pubmed-meshheading:15967798-Immunoprecipitation,
pubmed-meshheading:15967798-Interleukin-1,
pubmed-meshheading:15967798-Iron,
pubmed-meshheading:15967798-Liver,
pubmed-meshheading:15967798-Luciferases,
pubmed-meshheading:15967798-Molecular Sequence Data,
pubmed-meshheading:15967798-Plasmids,
pubmed-meshheading:15967798-Poly C,
pubmed-meshheading:15967798-Pregnancy Proteins,
pubmed-meshheading:15967798-Protein Binding,
pubmed-meshheading:15967798-Protein Biosynthesis,
pubmed-meshheading:15967798-Protein Structure, Secondary,
pubmed-meshheading:15967798-Protein Structure, Tertiary,
pubmed-meshheading:15967798-RNA, Messenger,
pubmed-meshheading:15967798-Recombinant Proteins,
pubmed-meshheading:15967798-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:15967798-Time Factors,
pubmed-meshheading:15967798-Transfection,
pubmed-meshheading:15967798-Ultraviolet Rays
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pubmed:year |
2005
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pubmed:articleTitle |
The acute box cis-element in human heavy ferritin mRNA 5'-untranslated region is a unique translation enhancer that binds poly(C)-binding proteins.
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pubmed:affiliation |
Laboratory for Cancer Medicine, School of Medicine and Pharmacology, UWA Centre for Medical Research, Western Australian Institute for Medical Research and University of Western Australia, Royal Perth Hospital.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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