1281544

pubmed:Citation

24

The translation of ferritin mRNA and degradation of transferrin receptor mRNA are regulated by the interaction of an RNA-binding protein, the iron-responsive element binding protein (IRE-BP), with RNA stem-loop structures known as iron-responsive elements (IREs) contained within these transcripts. IRE-BP produced in iron-replete cells has aconitase (EC 4.2.1.3) activity. The protein shows extensive sequence homology with mitochondrial aconitase, and sequences of peptides prepared from cytosolic aconitase are identical with peptides of IRE-BP. As an active aconitase, IRE-BP is expected to have an Fe-S cluster, in analogy to other aconitases. This Fe-S cluster has been implicated as the region of the protein that senses intracellular iron levels and accordingly modifies the ability of the IRE-BP to interact with IREs. Expression of the IRE-BP in cultured cells has revealed that the IRE-BP functions either as an active aconitase, when the cells are iron-replete, or as an active RNA-binding protein, when the cells are iron-depleted. We compare properties of purified authentic cytosolic aconitase from beef liver with those of IRE-BP from tissue culture cells and establish that characteristics of the physiologically relevant form of the protein from iron-depleted cells resemble those of cytosolic aconitase apoprotein. We demonstrate that loss of the labile fourth iron atom of the Fe-S cluster results in loss of aconitase activity, but that more extensive cluster alteration is required before the IRE-BP acquires the capacity to bind RNA with the affinity seen in vivo. These results are consistent with a model in which the cubane Fe-S cluster is disassembled when intracellular iron is depleted.

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http://linkedlifedata.com/resource/pubmed/journal/7505876

http://linkedlifedata.com/resource/pubmed/chemical/Aconitate Hydratase, http://linkedlifedata.com/resource/pubmed/chemical/Apoproteins, http://linkedlifedata.com/resource/pubmed/chemical/Deferoxamine, http://linkedlifedata.com/resource/pubmed/chemical/Ferricyanides, http://linkedlifedata.com/resource/pubmed/chemical/Ferritins, http://linkedlifedata.com/resource/pubmed/chemical/Hemin, http://linkedlifedata.com/resource/pubmed/chemical/Iron, http://linkedlifedata.com/resource/pubmed/chemical/Iron-Regulatory Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Iron-Sulfur Proteins, http://linkedlifedata.com/resource/pubmed/chemical/RNA, http://linkedlifedata.com/resource/pubmed/chemical/RNA-Binding Proteins, http://linkedlifedata.com/resource/pubmed/chemical/hexacyanoferrate III

Dec

pubmed-author:BeinertHH, pubmed-author:BlondinG AGA, pubmed-author:HaileD JDJ, pubmed-author:HarfordJ BJB, pubmed-author:KennedyM CMC, pubmed-author:KlausnerR DRD, pubmed-author:RouaultT ATA

15

NLM

11735-9

pubmed-meshheading:1281544-Aconitate Hydratase, pubmed-meshheading:1281544-Animals, pubmed-meshheading:1281544-Apoproteins, pubmed-meshheading:1281544-Deferoxamine, pubmed-meshheading:1281544-Ferricyanides, pubmed-meshheading:1281544-Ferritins, pubmed-meshheading:1281544-Hemin, pubmed-meshheading:1281544-Humans, pubmed-meshheading:1281544-Iron, pubmed-meshheading:1281544-Iron-Regulatory Proteins, pubmed-meshheading:1281544-Iron-Sulfur Proteins, pubmed-meshheading:1281544-Mice, pubmed-meshheading:1281544-Oxidation-Reduction, pubmed-meshheading:1281544-RNA, pubmed-meshheading:1281544-RNA-Binding Proteins, pubmed-meshheading:1281544-Structure-Activity Relationship, pubmed-meshheading:1281544-Tumor Cells, Cultured

Cellular regulation of the iron-responsive element binding protein: disassembly of the cubane iron-sulfur cluster results in high-affinity RNA binding.

Journal Article, In Vitro, Research Support, U.S. Gov't, P.H.S.