ArticleThe Journal of biological chemistry2013
F-box and leucine-rich repeat protein 5 (FBXL5) is required for maintenance of cellular and systemic iron homeostasis.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 44 citations in OpenAlex.
- Tracking Intracellular Labile Iron with a Genetically Encoded Fluorescent Reporter System Based on Protein Stability.ACS sensors · 2025Article
- Transcriptome analysis of iron over-accumulating Arabidopsis genotypes uncover putative novel regulators of systemic and retrograde signaling.The plant genome · 2024Article
- Prenatal exome sequencing: A useful tool for the fetal neurologist.Clinical genetics · 2022Article
- Inflaming the Brain with Iron.Antioxidants (Basel, Switzerland) · 2021Review
- Iron Dyshomeostasis Participated in Rat Hippocampus Toxicity Caused by Aluminum Chloride.Biological trace element research · 2020Article
- Metabolic reprogramming ofMicrobial cell (Graz, Austria) · 2019Article
- Disruption of FBXL5-mediated cellular iron homeostasis promotes liver carcinogenesis.The Journal of experimental medicine · 2019Article
- Mutant huntingtin induces iron overload via up-regulating IRP1 in Huntington's disease.Cell & bioscience · 2018Article
- Ferredoxin reductase is critical for p53-dependent tumor suppression via iron regulatory protein 2.Genes & development · 2017Article
- Modular transcriptional repertoire and MicroRNA target analyses characterize genomic dysregulation in the thymus of Down syndrome infants.Oncotarget · 2016Article
- Deregulation of F-box proteins and its consequence on cancer development, progression and metastasis.Seminars in cancer biology · 2016Review
- Regulation of iron homeostasis by the p53-ISCU pathway.Scientific reports · 2015Article
- Iron-sulfur cluster biogenesis in mammalian cells: New insights into the molecular mechanisms of cluster delivery.Biochimica et biophysica acta · 2015Review
- Deciphering Mineral Homeostasis in Barley Seed Transfer Cells at Transcriptional Level.PloS one · 2015Article
- Iron-binding E3 ligase mediates iron response in plants by targeting basic helix-loop-helix transcription factors.Plant physiology · 2015Article
- Endogenous bone regeneration is dependent upon a dynamic oxygen event.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2014Article
- FBXL5 targets cortactin for ubiquitination-mediated destruction to regulate gastric cancer cell migration.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014Article
- Diversity of the metal-transporting P1B-type ATPases.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2014Article
- F-box and leucine-rich repeat protein 5 (FBXL5): sensing intracellular iron and oxygen.Journal of inorganic biochemistry · 2014Review
- Roles of F-box proteins in cancer.Nature reviews. Cancer · 2014Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Maintenance of cellular iron homeostasis requires post-transcriptional regulation of iron metabolism genes by iron regulatory protein 2 (IRP2). The hemerythrin-like domain of F-box and leucine-rich repeat protein 5 (FBXL5), an E3 ubiquitin ligase subunit, senses iron and oxygen availability and facilitates IRP2 degradation in iron replete cells. Disruption of the ubiquitously expressed murine Fbxl5 gene results in a failure to sense increased cellular iron availability, accompanied by constitutive IRP2 accumulation and misexpression of IRP2 target genes. FBXL5-null mice die during embryogenesis, although viability is restored by simultaneous deletion of the IRP2, but not IRP1, gene. Mice containing a single functional Fbxl5 allele behave like their wild type littermates when fed an iron-sufficient diet. However, unlike wild type mice that manifest decreased hematocrit and hemoglobin levels when fed a low-iron diet, Fbxl5 heterozygotes maintain normal hematologic values due to increased iron absorption. The responsiveness of IRP2 to low iron is specifically enhanced in the duodena of the heterozygotes and is accompanied by increased expression of the divalent metal transporter-1. These results confirm the role of FBXL5 in the in vivo maintenance of cellular and systemic iron homeostasis and reveal a privileged role for the intestine in their regulation by virtue of its unique FBXL5 iron sensitivity.
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Registered trials
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