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Article: Identification of a hypoxia response element in the transferrin receptor gene

TitleIdentification of a hypoxia response element in the transferrin receptor gene
Authors
Issue Date1999
PublisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/
Citation
Journal Of Biological Chemistry, 1999, v. 274 n. 34, p. 24147-24152 How to Cite?
AbstractExpression of the transferrin receptor, which mediates iron uptake from transferrin, is negatively regulated post-transcriptionally by intracellular iron through iron-responsive elements in the 3'-untranslated region of the transferrin receptor mRNA. Transcriptional mechanisms are also involved in receptor expression, but these are poorly understood. In this study we have characterized the transferrin receptor promoter region and identified a functional hypoxia response element that contains a binding site for hypoxia- inducible factor-1 (HIF-1). Exposure of K562 and HeLa cells to hypoxia for 16 h resulted in a 2- to 3-fold increase in transferrin receptor mRNA expression. A motif with multipartite organization similar to the hypoxia response element of a number of hypoxia-inducible genes such as erythropoietin was identified within a 100-base pair sequence upstream of the transcriptional start site. Mutation of a site similar to the consensus HIF- binding site (HBS) in this motif attenuated the hypoxic response by 80%. Transient co-expression of the two HIF-1 subunits (HIF-1α and HIF-1β) enhanced the wild type transferrin receptor promoter activity, but that which contained a mutated HBS yielded no such response. Electrophoretic mobility shift assays revealed that HIF-1 was stimulated and bound to the transferrin receptor HBS upon hypoxic challenge. Our results indicate that the transferrin receptor is a target gene for HIF-1.
Persistent Identifierhttp://hdl.handle.net/10722/167287
ISSN
2015 Impact Factor: 4.258
2015 SCImago Journal Rankings: 3.151
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLok, CNen_US
dc.contributor.authorPonka, Pen_US
dc.date.accessioned2012-10-08T03:05:17Z-
dc.date.available2012-10-08T03:05:17Z-
dc.date.issued1999en_US
dc.identifier.citationJournal Of Biological Chemistry, 1999, v. 274 n. 34, p. 24147-24152en_US
dc.identifier.issn0021-9258en_US
dc.identifier.urihttp://hdl.handle.net/10722/167287-
dc.description.abstractExpression of the transferrin receptor, which mediates iron uptake from transferrin, is negatively regulated post-transcriptionally by intracellular iron through iron-responsive elements in the 3'-untranslated region of the transferrin receptor mRNA. Transcriptional mechanisms are also involved in receptor expression, but these are poorly understood. In this study we have characterized the transferrin receptor promoter region and identified a functional hypoxia response element that contains a binding site for hypoxia- inducible factor-1 (HIF-1). Exposure of K562 and HeLa cells to hypoxia for 16 h resulted in a 2- to 3-fold increase in transferrin receptor mRNA expression. A motif with multipartite organization similar to the hypoxia response element of a number of hypoxia-inducible genes such as erythropoietin was identified within a 100-base pair sequence upstream of the transcriptional start site. Mutation of a site similar to the consensus HIF- binding site (HBS) in this motif attenuated the hypoxic response by 80%. Transient co-expression of the two HIF-1 subunits (HIF-1α and HIF-1β) enhanced the wild type transferrin receptor promoter activity, but that which contained a mutated HBS yielded no such response. Electrophoretic mobility shift assays revealed that HIF-1 was stimulated and bound to the transferrin receptor HBS upon hypoxic challenge. Our results indicate that the transferrin receptor is a target gene for HIF-1.en_US
dc.languageengen_US
dc.publisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/en_US
dc.relation.ispartofJournal of Biological Chemistryen_US
dc.subject.meshBase Sequenceen_US
dc.subject.meshCell Hypoxia - Geneticsen_US
dc.subject.meshDna-Binding Proteins - Physiologyen_US
dc.subject.meshGene Expression Regulationen_US
dc.subject.meshHela Cellsen_US
dc.subject.meshHumansen_US
dc.subject.meshHypoxia-Inducible Factor 1en_US
dc.subject.meshHypoxia-Inducible Factor 1, Alpha Subuniten_US
dc.subject.meshIron - Metabolismen_US
dc.subject.meshIron-Regulatory Proteinsen_US
dc.subject.meshIron-Sulfur Proteins - Metabolismen_US
dc.subject.meshK562 Cellsen_US
dc.subject.meshMolecular Sequence Dataen_US
dc.subject.meshNuclear Proteins - Physiologyen_US
dc.subject.meshPromoter Regions, Geneticen_US
dc.subject.meshRna-Binding Proteins - Metabolismen_US
dc.subject.meshReceptors, Transferrin - Geneticsen_US
dc.subject.meshResponse Elementsen_US
dc.subject.meshTranscription Factorsen_US
dc.titleIdentification of a hypoxia response element in the transferrin receptor geneen_US
dc.typeArticleen_US
dc.identifier.emailLok, CN:cnlok@hku.hken_US
dc.identifier.authorityLok, CN=rp00752en_US
dc.description.naturelink_to_OA_fulltexten_US
dc.identifier.doi10.1074/jbc.274.34.24147en_US
dc.identifier.pmid10446188-
dc.identifier.scopuseid_2-s2.0-0000655498en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0000655498&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume274en_US
dc.identifier.issue34en_US
dc.identifier.spage24147en_US
dc.identifier.epage24152en_US
dc.identifier.isiWOS:000082110900067-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridLok, CN=7006410829en_US
dc.identifier.scopusauthoridPonka, P=7004508750en_US

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