ArticleThe EMBO journal2006
Iron-responsive degradation of iron-regulatory protein 1 does not require the Fe-S cluster.
Article in The EMBO journal, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
43 citing papers in PubMed, 95 citations in OpenAlex.
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- The detrimental effect of iron on OA chondrocytes: Importance of pro-inflammatory cytokines induced iron influx and oxidative stress.Journal of cellular and molecular medicine · 2021Article
- Understanding protein multifunctionality: from short linear motifs to cellular functions.Cellular and molecular life sciences : CMLS · 2019Review
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- 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
- Oxidative stress and the homeodynamics of iron metabolism.Biomolecules · 2015Review
- Heme and erythropoieis: more than a structural role.Haematologica · 2014Review
- Iron regulatory protein-1 protects against mitoferrin-1-deficient porphyria.The Journal of biological chemistry · 2014Article
- The IRP/IRE system in vivo: insights from mouse models.Frontiers in pharmacology · 2014Review
- Human CIA2A-FAM96A and CIA2B-FAM96B integrate iron homeostasis and maturation of different subsets of cytosolic-nuclear iron-sulfur proteins.Cell metabolism · 2013Article
- 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
- F-box and leucine-rich repeat protein 5 (FBXL5) is required for maintenance of cellular and systemic iron homeostasis.The Journal of biological chemistry · 2013Article
- Protein degradation and iron homeostasis.Biochimica et biophysica acta · 2012Review
- The regulation of AβPP expression by RNA-binding proteins.Ageing research reviews · 2012Review
- Mammalian iron metabolism and its control by iron regulatory proteins.Biochimica et biophysica acta · 2012Review
- Mechanisms of mammalian iron homeostasis.Biochemistry · 2012Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
The generally accepted role of iron-regulatory protein 1 (IRP1) in orchestrating the fate of iron-regulated mRNAs depends on the interconversion of its cytosolic aconitase and RNA-binding forms through assembly/disassembly of its Fe-S cluster, without altering protein abundance. Here, we show that IRP1 protein abundance can be iron-regulated. Modulation of IRP1 abundance by iron did not require assembly of the Fe-S cluster, since a mutant with all cluster-ligating cysteines mutated to serine underwent iron-induced protein degradation. Phosphorylation of IRP1 at S138 favored the RNA-binding form and promoted iron-dependent degradation. However, phosphorylation at S138 was not required for degradation. Further, degradation of an S138 phosphomimetic mutant was not blocked by mutation of cluster-ligating cysteines. These findings were confirmed in mouse models with genetic defects in cytosolic Fe-S cluster assembly/disassembly. IRP1 RNA-binding activity was primarily regulated by IRP1 degradation in these animals. Our results reveal a mechanism for regulating IRP1 action relevant to the control of iron homeostasis during cell proliferation, inflammation, and in response to diseases altering cytosolic Fe-S cluster assembly or disassembly.
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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.