ArticleMolecular and cellular biology2002
Conditional derepression of ferritin synthesis in cells expressing a constitutive IRP1 mutant.
Article in Molecular and cellular biology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 48 citations in OpenAlex.
- Transport pathways across the blood-brain barrier for waste clearance and drug delivery.Fluids and barriers of the CNS · 2026Review
- Expression of genes related to iron homeostasis in breast cancer.Molecular biology reports · 2023Article
- Identification and Characterization of Glycine Decarboxylase as a Direct Target of Snail in the Epithelial-Mesenchymal Transition of Cancer Cells.Tumor & microenvironment · 2021Article
- Mdm2 is a target and mediator of IRP2 in cell growth control.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Perturbation of Iron Metabolism by Cisplatin through Inhibition of Iron Regulatory Protein 2.Cell chemical biology · 2019Article
- Loss of ABHD5 promotes the aggressiveness of prostate cancer cells.Scientific reports · 2017Article
- Iron homeostasis and tumorigenesis: molecular mechanisms and therapeutic opportunities.Protein & cell · 2015Review
- The IRP/IRE system in vivo: insights from mouse models.Frontiers in pharmacology · 2014Review
- Abnormal body iron distribution and erythropoiesis in a novel mouse model with inducible gain of iron regulatory protein (IRP)-1 function.Journal of molecular medicine (Berlin, Germany) · 2013Article
- Alternative ferritin mRNA translation via internal initiation.RNA (New York, N.Y.) · 2012Article
- Regulation of cellular iron metabolism.The Biochemical journal · 2011Review
- Tumorigenic properties of iron regulatory protein 2 (IRP2) mediated by its specific 73-amino acids insert.PloS one · 2010Article
- Regulating amyloid precursor protein synthesis through an internal ribosomal entry site.Nucleic acids research · 2008Article
- Iron-dependent degradation of IRP2 requires its C-terminal region and IRP structural integrity.BMC molecular biology · 2008Article
- Human iron regulatory protein 2 is easily cleaved in its specific domain: consequences for the haem binding properties of the protein.The Biochemical journal · 2007Article
- Iron-dependent degradation of apo-IRP1 by the ubiquitin-proteasome pathway.Molecular and cellular biology · 2007Article
- Overexpression of iron regulatory protein 1 suppresses growth of tumor xenografts.Carcinogenesis · 2007Article
- Molecular control of vertebrate iron homeostasis by iron regulatory proteins.Biochimica et biophysica acta · 2006Review
- Iron-responsive degradation of iron-regulatory protein 1 does not require the Fe-S cluster.The EMBO journal · 2006Article
- Inhibition of transferrin receptor 1 transcription by a cell density response element.The Biochemical journal · 2005Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Iron regulatory protein 1 (IRP1), a major posttranscriptional regulator of cellular iron and energy metabolism, is controlled by an iron-sulfur cluster switch. Cysteine-437 is critical for coordinating the cluster, and its replacement yields mutants that do not respond to iron perturbations and constitutively bind to cognate mRNA iron-responsive elements (IREs). The expression of IRP1(C437S) in cells has been associated with aberrations in iron homeostasis and toxicity. We have established clones of human lung (H1299) and breast (MCF7) cancer cells that express high levels of IRP1(C437S) in a tetracycline-inducible manner. As expected, IRP1(C437S) stabilizes transferrin receptor mRNA and inhibits translation of ferritin mRNA in both cell types by binding to their respective IREs. However, H1299 transfectants grown at high densities are able to overcome the IRP1(C437S)-mediated inhibition in ferritin synthesis. The mechanism involves neither alteration in ferritin mRNA levels nor utilization of alternative transcription start sites to eliminate the IRE or relocate it in less inhibitory downstream positions. The derepression of ferritin mRNA translation occurs under conditions where global protein synthesis appears to be impaired, as judged by a significant enrichment in the expression of the underphosphorylated form of the translational regulator 4E-BP1. Collectively, these data document an example where ferritin mRNA translation evades control of the IRE-IRP system. The physiological implications of this response are reflected in protection against iron-mediated toxicity, oxidative stress, and apoptosis.
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