Regulation of genes of iron metabolism by the iron-response proteins.
Iron is an essential nutrient, yet excess iron can be toxic to cells. The uptake of iron by mammalian cells is post-transcriptionally regulated by the interaction of iron-response proteins (IRP1 and IRP2) with iron-response elements (IREs) found in the mRNAs of genes of iron metabolism, such as ferritin, the transferrin receptor, erythroid aminolevulinic acid synthase, and mitochondrial aconitase. The IRPs are RNA binding proteins that bind to the IRE (found in the mRNAs of the regulated genes) in an iron- dependent manner. Binding of IRPs to the IREs leads to changes in the expression of the regulated genes and subsequent changes in the uptake, utilization, or storage of intracellular iron. Recent work has demonstrated that the binding of the IRPs to the IREs can also be modulated by changes in the redox state or oxidative stress level of the cell. These findings provide an important link between iron metabolism and states of oxidative stress.
Haile
D J
DJ
Department of Medicine, University of Texas Health Science Center at San Antonio, 78284-7880, USA.
D000154:Aconitate Hydratase / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D005786:Gene Expression Regulation; D006801:Humans; D007501:Iron / Q000378:metabolism*; D035941:Iron Regulatory Protein 1; D035942:Iron Regulatory Protein 2; D035925:Iron-Regulatory Proteins; D007506:Iron-Sulfur Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D018384:Oxidative Stress; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D011990:Receptors, Transferrin / Q000378:metabolism*
D035925:Iron-Regulatory Proteins; D007506:Iron-Sulfur Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D011990:Receptors, Transferrin; D007501:Iron; D000154:Aconitate Hydratase; D035941:Iron Regulatory Protein 1; D035942:Iron Regulatory Protein 2