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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
21
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pubmed:dateCreated |
1999-12-2
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pubmed:abstractText |
Treatment with iron chelators mimics hypoxic induction of the hypoxia inducible factor (HIF-1) which activates transcription by binding to hypoxia responsive elements (HRE). We investigated whether HIF-1 is involved in transcriptional activation of the transferrin receptor (TfR), a membrane protein which mediates cellular iron uptake, in response to iron deprivation. The transcription rate of the TfR gene in isolated nuclei was up-regulated by treatment of Hep3B human hepatoma cells with the iron chelator desferrioxamine (DFO). The role of HIF-1 in the activation of TfR was indicated by the following observations: (i) DFO-dependent activation of a luciferase reporter gene in transfected Hep3B cells was mediated by a fragment of the human TfR promoter containing a putative HRE sequence; (ii) mutation of this sequence prevented stimulation of luciferase activity; (iii) binding to this sequence of HIF-1alpha, identified by competition experiments and supershift assays, was induced by DFO. Furthermore, in mouse hepatoma cells unable to assemble functional HIF-1, inducibility of TfR transcription by DFO was lost and TfR mRNA up-regulation was reduced. These results, which show the role of HIF-1 in the control of TfR gene expression in conditions of iron depletion, give insights into the mechanisms of transcriptional regulation which concur with the well-characterized post-transcriptional control of TfR expression to expand the extent of response to iron deficiency.
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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/Cobalt,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Deferoxamine,
http://linkedlifedata.com/resource/pubmed/chemical/HIF1A protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Hif1a protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Hypoxia-Inducible Factor 1,
http://linkedlifedata.com/resource/pubmed/chemical/Hypoxia-Inducible Factor 1, alpha...,
http://linkedlifedata.com/resource/pubmed/chemical/Iron,
http://linkedlifedata.com/resource/pubmed/chemical/Iron Chelating Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Transferrin,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/cobaltous chloride
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
1362-4962
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
1
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pubmed:volume |
27
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4223-7
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:10518614-Animals,
pubmed-meshheading:10518614-Base Sequence,
pubmed-meshheading:10518614-Carcinoma, Hepatocellular,
pubmed-meshheading:10518614-Cell Hypoxia,
pubmed-meshheading:10518614-Cobalt,
pubmed-meshheading:10518614-DNA,
pubmed-meshheading:10518614-DNA-Binding Proteins,
pubmed-meshheading:10518614-Deferoxamine,
pubmed-meshheading:10518614-Humans,
pubmed-meshheading:10518614-Hypoxia-Inducible Factor 1,
pubmed-meshheading:10518614-Hypoxia-Inducible Factor 1, alpha Subunit,
pubmed-meshheading:10518614-Iron,
pubmed-meshheading:10518614-Iron Chelating Agents,
pubmed-meshheading:10518614-Mice,
pubmed-meshheading:10518614-Mutation,
pubmed-meshheading:10518614-Nuclear Proteins,
pubmed-meshheading:10518614-Promoter Regions, Genetic,
pubmed-meshheading:10518614-Receptors, Transferrin,
pubmed-meshheading:10518614-Response Elements,
pubmed-meshheading:10518614-Transcription, Genetic,
pubmed-meshheading:10518614-Transcription Factors,
pubmed-meshheading:10518614-Transcriptional Activation,
pubmed-meshheading:10518614-Transfection,
pubmed-meshheading:10518614-Tumor Cells, Cultured
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pubmed:year |
1999
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pubmed:articleTitle |
HIF-1-mediated activation of transferrin receptor gene transcription by iron chelation.
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pubmed:affiliation |
Istituto di Patologia Generale and Istituto Scienze Mediche, IRCCS Ospedale Maggiore, Università di Milano, Italy.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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