scholarly journals Identification of a Heme-sensing Domain in Iron Regulatory Protein 2

2004 ◽  
Vol 279 (44) ◽  
pp. 45450-45454 ◽  
Author(s):  
Jinsook Jeong ◽  
Tracey A. Rouault ◽  
Rodney L. Levine
Keyword(s):  
Cytochrome P450 ◽  
Iron Deficiency ◽  
Iron Metabolism ◽  
Regulatory Protein ◽  
Protein Molecule ◽  
Covalent Modification ◽  
Iron Regulatory Protein ◽  
Cellular Regulation ◽  
High Affinity ◽  
Iron Responsive Elements

Iron regulatory protein 2 coordinates the cellular regulation of iron metabolism by binding to iron-responsive elements in mRNA. The protein is synthesized constitutively but is rapidly degraded when iron stores are replete. The mechanisms that prevent degradation during iron deficiency or promote degradation during iron sufficiency are not delineated. Iron regulatory protein 2 contains a domain not present in the closely related iron regulatory protein 1, and we found that this domain binds heme with high affinity. A cysteine within the domain is axially liganded to the heme, as occurs in cytochrome P450. The protein-bound heme reacts with molecular oxygen to mediate the oxidation of cysteine, including β-elimination of the sulfur to yield alanine. This covalent modification may thus mark the protein molecule for degradation by the proteasome system, providing another mechanism by which heme can regulate the level of iron regulatory protein 2.

HBx modulates iron regulatory protein 1-mediated iron metabolism via reactive oxygen species

2008 ◽  
Vol 133 (2) ◽  
pp. 167-177 ◽  
Author(s):  
Jin-Mo Gu ◽  
Seung Oe Lim ◽  
Sae Jin Oh ◽  
So-Mi Yoon ◽  
Je Kyung Seong ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Iron Metabolism ◽  
Regulatory Protein ◽  
Reactive Oxygen ◽  
Iron Regulatory Protein ◽  
Oxygen Species ◽  
Iron Regulatory Protein 1

Targeted deletion of the gene encoding iron regulatory protein-2 causes misregulation of iron metabolism and neurodegenerative disease in mice

10.1038/84859 ◽  
2001 ◽  
Vol 27 (2) ◽  
pp. 209-214 ◽  
Author(s):  
Timothy LaVaute ◽  
Sophia Smith ◽  
Sharon Cooperman ◽  
Kazuhiro Iwai ◽  
William Land ◽  
...  
Keyword(s):  
Neurodegenerative Disease ◽  
Iron Metabolism ◽  
Regulatory Protein ◽  
Iron Regulatory Protein ◽  
Gene Encoding ◽  
Targeted Deletion

scholarly journals Regulation of Cellular Iron Metabolism by Erythropoietin: Activation of Iron-Regulatory Protein and Upregulation of Transferrin Receptor Expression in Erythroid Cells

Blood ◽  
1997 ◽  
Vol 89 (2) ◽  
pp. 680-687 ◽  
Author(s):  
Günter Weiss ◽  
Tracey Houston ◽  
Stefan Kastner ◽  
Karin Jöhrer ◽  
Kurt Grünewald ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Iron Metabolism ◽  
Transferrin Receptor ◽  
Regulatory Protein ◽  
Receptor Expression ◽  
General Mechanism ◽  
Iron Regulatory Protein ◽  
Erythroid Progenitor ◽  
Cellular Iron ◽  
Erythroid Progenitor Cells

Abstract Erythropoietin (Epo) is the central regulator of red blood cell production and acts primarily by inducing proliferation and differentiation of erythroid progenitor cells. Because a sufficient supply of iron is a prerequisite for erythroid proliferation and hemoglobin synthesis, we have investigated whether Epo can regulate cellular iron metabolism. We present here a novel biologic function of Epo, namely as a potential modulator of cellular iron homeostasis. We show that, in human (K562) and murine erythroleukemic cells (MEL), Epo enhances the binding affinity of iron-regulatory protein (IRP)-1, the central regulator of cellular iron metabolism, to specific RNA stem-loop structures, known as iron-responsive elements (IREs). Activation of IRP-1 by Epo is associated with a marked increase in transferrin receptor (trf-rec) mRNA levels in K562 and MEL, enhanced cell surface expression of trf-recs, and increased uptake of iron into cells. These findings are in agreement with the well-established mechanism whereby high-affinity binding of IRPs to IREs stabilizes trf-rec mRNA by protecting it from degradation by a specific RNase. The effects of Epo on IRE-binding of IRPs were not observed in human myelomonocytic cells (THP-1), which indicates that this response to Epo is not a general mechanism observed in all cells but is likely to be erythroid-specific. Our results provide evidence for a direct functional connection between Epo biology and iron metabolism by which Epo increases iron uptake into erythroid progenitor cells via posttranscriptional induction of trf-rec expression. Our data suggest that sequential administration of Epo and iron might improve the response to Epo therapy in some anemias.

scholarly journals Speciation of iron in mouse liver during development, iron deficiency, IRP2 deletion and inflammatory hepatitis

Metallomics ◽  
2015 ◽  
Vol 7 (1) ◽  
pp. 93-101 ◽  
Author(s):  
Mrinmoy Chakrabarti ◽  
Allison L. Cockrell ◽  
Jinkyu Park ◽  
Sean P. McCormick ◽  
Lora S. Lindahl ◽  
...  
Keyword(s):  
Mössbauer Spectroscopy ◽  
Iron Deficiency ◽  
Mouse Liver ◽  
Mossbauer Spectroscopy ◽  
Regulatory Protein ◽  
Iron Regulatory Protein ◽  
Mößbauer Spectroscopy ◽  
Fe Content

Mössbauer spectroscopy was used to evaluate the Fe content of 57Fe-enriched livers during development, Fe-deficient conditions, in mice suffering from inflammatory hepatitis, and in mice lacking an iron regulatory protein.

scholarly journals Perturbation of Iron Metabolism by Cisplatin through Inhibition of Iron Regulatory Protein 2

2019 ◽  
Vol 26 (1) ◽  
pp. 85-97.e4 ◽  
Author(s):  
Masaki Miyazawa ◽  
Alexander R. Bogdan ◽  
Yoshiaki Tsuji
Keyword(s):  
Iron Metabolism ◽  
Regulatory Protein ◽  
Iron Regulatory Protein
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