scholarly journals Sustained Hydrogen Peroxide Induces Iron Uptake by Transferrin Receptor-1 Independent of the Iron Regulatory Protein/Iron-responsive Element Network

2007 ◽  
Vol 282 (28) ◽  
pp. 20301-20308 ◽  
Author(s):  
Bill Andriopoulos ◽  
Stephan Hegedüsch ◽  
Julia Mangin ◽  
Hans-Dieter Riedel ◽  
Ulrike Hebling ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Transferrin Receptor ◽  
Iron Uptake ◽  
Regulatory Protein ◽  
Iron Regulatory Protein ◽  
Iron Responsive Element ◽  
Transferrin Receptor 1 ◽  
Responsive Element

scholarly journals Cysteine Oxidation Regulates the RNA-Binding Activity of Iron Regulatory Protein 2

2009 ◽  
Vol 29 (8) ◽  
pp. 2219-2229 ◽  
Author(s):  
Kimberly B. Zumbrennen ◽  
Michelle L. Wallander ◽  
S. Joshua Romney ◽  
Elizabeth A. Leibold
Keyword(s):  
Oxidative Stress ◽  
Transferrin Receptor ◽  
Iron Homeostasis ◽  
Rna Binding ◽  
Regulatory Protein ◽  
Binding Activity ◽  
Structural Basis ◽  
Iron Regulatory Protein ◽  
Transferrin Receptor 1 ◽  
Binding Cleft

ABSTRACT Iron regulatory protein 2 (IRP2) is an RNA-binding protein that regulates the posttranscriptional expression of proteins required for iron homeostasis such as ferritin and transferrin receptor 1. IRP2 RNA-binding activity is primarily regulated by iron-mediated proteasomal degradation, but studies have suggested that IRP2 RNA binding is also regulated by thiol oxidation. We generated a model of IRP2 bound to RNA and found that two cysteines (C512 and C516) are predicted to lie in the RNA-binding cleft. Site-directed mutagenesis and thiol modification show that, while IRP2 C512 and C516 do not directly interact with RNA, both cysteines are located within the RNA-binding cleft and must be unmodified/reduced for IRP2-RNA interactions. Oxidative stress induced by cellular glucose deprivation reduces the RNA-binding activity of IRP2 but not IRP2-C512S or IRP2-C516S, consistent with the formation of a disulfide bond between IRP2 C512 and C516 during oxidative stress. Decreased IRP2 RNA binding is correlated with reduced transferrin receptor 1 mRNA abundance. These studies provide insight into the structural basis for IRP2-RNA interactions and reveal an iron-independent mechanism for regulating iron homeostasis through the redox regulation of IRP2 cysteines.

scholarly journals Loops and Bulge/Loops in Iron-responsive Element Isoforms Influence Iron Regulatory Protein Binding

1998 ◽  
Vol 273 (37) ◽  
pp. 23637-23640 ◽  
Author(s):  
Yaohuang Ke ◽  
Jingyang Wu ◽  
Elizabeth A. Leibold ◽  
William E. Walden ◽  
Elizabeth C. Theil
Keyword(s):  
Protein Binding ◽  
Regulatory Protein ◽  
Iron Regulatory Protein ◽  
Iron Responsive Element ◽  
Responsive Element
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