Regulation of the iron regulatory proteins by reactive nitrogen and oxygen species.
Iron regulatory proteins 1 and 2 (IRP1 and IRP2) are RNA binding proteins that posttranscriptionally regulate the expression of mRNAs coding for proteins involved in the maintenance of iron and energy homeostasis. The RNA binding activities of the IRPs are regulated by changes in cellular iron. Thus, the IRPs are considered iron sensors and the principle regulators of cellular iron homeostasis. The mechanisms governing iron regulation of the IRPs are well described. Recently, however, much attention has focused on the regulation of IRPs by reactive nitrogen and oxygen species (RNS, ROS). Here we focus on summarizing the iron-regulated RNA binding activities of the IRPs, as well as the recent findings of IRP regulation by RNS and ROS. The recent observations that changes in oxygen tension regulate both IRP1 and IRP2 RNA binding activities will be addressed in light of ROS regulation of the IRPs.
Hanson
E S
ES
Department of Medicine, University of Utah, Salt Lake City 84112, USA.
Leibold
E A
EA
D000818:Animals; D006706:Homeostasis; D007501:Iron / Q000378:metabolism; D035941:Iron Regulatory Protein 1; D035942:Iron Regulatory Protein 2; D035925:Iron-Regulatory Proteins; D007506:Iron-Sulfur Proteins / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D009584:Nitrogen / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*
D035925:Iron-Regulatory Proteins; D007506:Iron-Sulfur Proteins; D016601:RNA-Binding Proteins; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D007501:Iron; D035941:Iron Regulatory Protein 1; D035942:Iron Regulatory Protein 2; D009584:Nitrogen