ArticleMolecular and cellular biology2009
Cysteine oxidation regulates the RNA-binding activity of iron regulatory protein 2.
Article in Molecular and cellular biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed.
- Low Wall Shear Stress Promotes Atheroma via Arterial Iron Accumulation.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- Lipid metabolic reprogramming of hepatic CD4Microbiology spectrum · 2023Article
- Iron regulatory proteins: players or pawns in ferroptosis and cancer?Frontiers in molecular biosciences · 2023Review
- The Emerging Role of Deubiquitinases in Cell Death.Biomolecules · 2022Review
- New approaches to target RNA binding proteins.Current opinion in chemical biology · 2021Review
- Biochemistry of mammalian ferritins in the regulation of cellular iron homeostasis and oxidative responses.Science China. Life sciences · 2021Review
- The deubiquitinase OTUD1 enhances iron transport and potentiates host antitumor immunity.EMBO reports · 2021Article
- An Oxygen-Dependent Interaction between FBXL5 and the CIA-Targeting Complex Regulates Iron Homeostasis.Molecular cell · 2019Article
- Perturbation of Iron Metabolism by Cisplatin through Inhibition of Iron Regulatory Protein 2.Cell chemical biology · 2019Article
- The Roles of NRF2 in Modulating Cellular Iron Homeostasis.Antioxidants & redox signaling · 2018Review
- Function and crystal structure of the dimeric P-loop ATPase CFD1 coordinating an exposed [4Fe-4S] cluster for transfer to apoproteins.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- A synergistic role of IRP1 and FBXL5 proteins in coordinating iron metabolism during cell proliferation.The Journal of biological chemistry · 2017Article
- Fumarate Mediates a Chronic Proliferative Signal in Fumarate Hydratase-Inactivated Cancer Cells by Increasing Transcription and Translation of Ferritin Genes.Molecular and cellular biology · 2017Article
- NPGPx modulates CPEB2-controlled HIF-1α RNA translation in response to oxidative stress.Nucleic acids research · 2015Article
- The promoter and the 5'-untranslated region of rice metallothionein OsMT2b gene are capable of directing high-level gene expression in germinated rice embryos.Plant cell reports · 2014Article
- Iron transport through ferroportin is induced by intracellular ascorbate and involves IRP2 and HIF2α.Nutrients · 2014Article
- Aconitase post-translational modification as a key in linkage between Krebs cycle, iron homeostasis, redox signaling, and metabolism of reactive oxygen species.Redox report : communications in free radical research · 2014Review
- Human CIA2A-FAM96A and CIA2B-FAM96B integrate iron homeostasis and maturation of different subsets of cytosolic-nuclear iron-sulfur proteins.Cell metabolism · 2013Article
- Crucial function of vertebrate glutaredoxin 3 (PICOT) in iron homeostasis and hemoglobin maturation.Molecular biology of the cell · 2013Article
- Two roles for aconitase in the regulation of tricarboxylic acid branch gene expression in Bacillus subtilis.Journal of bacteriology · 2013Article
Corrections and comments
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4 authors.
Funding
Abstract
Iron regulatory protein 2 (IRP2) is an RNA-binding protein that regulates the posttranscriptional expression of proteins required for iron homeostasis such as ferritin and transferrin receptor 1. IRP2 RNA-binding activity is primarily regulated by iron-mediated proteasomal degradation, but studies have suggested that IRP2 RNA binding is also regulated by thiol oxidation. We generated a model of IRP2 bound to RNA and found that two cysteines (C512 and C516) are predicted to lie in the RNA-binding cleft. Site-directed mutagenesis and thiol modification show that, while IRP2 C512 and C516 do not directly interact with RNA, both cysteines are located within the RNA-binding cleft and must be unmodified/reduced for IRP2-RNA interactions. Oxidative stress induced by cellular glucose deprivation reduces the RNA-binding activity of IRP2 but not IRP2-C512S or IRP2-C516S, consistent with the formation of a disulfide bond between IRP2 C512 and C516 during oxidative stress. Decreased IRP2 RNA binding is correlated with reduced transferrin receptor 1 mRNA abundance. These studies provide insight into the structural basis for IRP2-RNA interactions and reveal an iron-independent mechanism for regulating iron homeostasis through the redox regulation of IRP2 cysteines.
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