ArticleProceedings of the National Academy of Sciences of the United States of America2014
Iron chaperones PCBP1 and PCBP2 mediate the metallation of the dinuclear iron enzyme deoxyhypusine hydroxylase.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
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Who cites it
78 citing papers in PubMed, 133 citations in OpenAlex.
- Trial
- Iron Homeostasis and Liver Diseases.Journal of cellular and molecular medicine · 2026Review
- Labile iron starvation in embryonic Kupffer cells aggravates MASH via mitochondrial failure and macrophage dysfunction.Cell death & disease · 2026Article
- Ferroptosis in neurological diseases: moving towards therapeutic intervention.Molecular psychiatry · 2026Review
- The Interaction Between Iron and Selenium Affects Ferroptosis in Colorectal Cancer.International journal of molecular sciences · 2026Review
- Iron-sensitive RNA regulation by poly C-binding proteins.Nucleic acids research · 2025Article
- PCBP2 in gastrointestinal cancers: fundamental mechanism and clinical potential.Journal of molecular medicine (Berlin, Germany) · 2025Review
- Acteoside ameliorates hepatocyte ferroptosis and hepatic ischemia-reperfusion injuryActa pharmaceutica Sinica. B · 2025Article
- PCBP2 as an intrinsic agi ng factor regulates the senescence of hBMSCs through the ROS-FGF2 signaling axis.eLife · 2025Article
- Human spindle-shaped urine-derived stem cell exosomes alleviate severe fatty liver ischemia-reperfusion injury by inhibiting ferroptosis via GPX4.Stem cell research & therapy · 2025Article
- Cellular Iron Homeostasis.Advances in experimental medicine and biology · 2025Review
- Nanomaterials targeting iron homeostasis: a promising strategy for cancer treatment.Frontiers in bioengineering and biotechnology · 2025Review
- Unraveling Ferroptosis: A New Frontier in Combating Renal Fibrosis and CKD Progression.Biology · 2024Review
- Why cells need iron: a compendium of iron utilisation.Trends in endocrinology and metabolism: TEM · 2024Review
- The link between amyloid β and ferroptosis pathway in Alzheimer's disease progression.Cell death & disease · 2024Article
- ATH434, a promising iron-targeting compound for treating iron regulation disorders.Metallomics : integrated biometal science · 2024Article
- Insights on the endogenous labile iron pool binding properties.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2024Article
- Article
- Metal ions overloading and cell death.Cell biology and toxicology · 2024Review
- The Ubiquity of the Reaction of the Labile Iron Pool That Attenuates Peroxynitrite-Dependent Oxidation Intracellularly.Biomolecules · 2024Article
18 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 3 countries.
Funding
Abstract
Although cells express hundreds of metalloenzymes, the mechanisms by which apoenzymes receive their metal cofactors are largely unknown. Poly(rC)-binding proteins PCBP1 and PCBP2 are multifunctional adaptor proteins that bind iron and deliver it to ferritin for storage or to prolyl and asparagyl hydroxylases to metallate the mononuclear iron center. Here, we show that PCBP1 and PCBP2 also deliver iron to deoxyhypusine hydroxylase (DOHH), the dinuclear iron enzyme required for hypusine modification of the translation factor eukaryotic initiation factor 5A. Cells depleted of PCBP1 or PCBP2 exhibited loss of DOHH activity and loss of the holo form of the enzyme in cells, particularly when cells were made mildly iron-deficient. Lysates containing PCBP1 and PCBP2 converted apo-DOHH to holo-DOHH in vitro with greater efficiency than lysates lacking PCBP1 or PCBP2. PCBP1 bound to DOHH in iron-treated cells but not in control or iron-deficient cells. Depletion of PCBP1 or PCBP2 had no effect on the cytosolic Fe-S cluster enzyme xanthine oxidase but led to loss of cytosolic aconitase activity. Loss of aconitase activity was not accompanied by gain of RNA-binding activity, a pattern suggesting the incomplete disassembly of the [4Fe-4S] cluster. PCBP depletions had minimal effects on total cellular iron, mitochondrial iron levels, and heme synthesis. Thus, PCBP1 and PCBP2 may serve as iron chaperones to multiple classes of cytosolic nonheme iron enzymes and may have a particular role in restoring metal cofactors that are spontaneously lost in iron deficient cells.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.