scholarly journals Inactivation of Both RNA Binding and Aconitase Activities of Iron Regulatory Protein-1 by Quinone-induced Oxidative Stress

1999 ◽  
Vol 274 (10) ◽  
pp. 6219-6225 ◽  
Author(s):  
Niels H. Gehring ◽  
Matthias W. Hentze ◽  
Kostas Pantopoulos
Keyword(s):  
Oxidative Stress ◽  
Rna Binding ◽  
Regulatory Protein ◽  
Iron Regulatory Protein ◽  
Iron Regulatory Protein 1

The Iron-Sulfur Cluster of Iron Regulatory Protein 1 Modulates the Accessibility of RNA Binding and Phosphorylation Sites†

Biochemistry ◽  
1997 ◽  
Vol 36 (13) ◽  
pp. 3950-3958 ◽  
Author(s):  
Kevin L. Schalinske ◽  
Sheila A. Anderson ◽  
Polygena T. Tuazon ◽  
Opal S. Chen ◽  
M. Claire Kennedy ◽  
...  
Keyword(s):  
Rna Binding ◽  
Regulatory Protein ◽  
Phosphorylation Sites ◽  
Iron Regulatory Protein ◽  
Iron Sulfur Cluster ◽  
Sulfur Cluster ◽  
Iron Sulfur ◽  
Iron Regulatory Protein 1

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 Differences in the Regulation of Iron Regulatory Protein-1 (IRP-1) by Extra- and Intracellular Oxidative Stress

1997 ◽  
Vol 272 (15) ◽  
pp. 9802-9808 ◽  
Author(s):  
Kostas Pantopoulos ◽  
Sebastian Mueller ◽  
Ann Atzberger ◽  
Wilhelm Ansorge ◽  
Wolfgang Stremmel ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Regulatory Protein ◽  
Iron Regulatory Protein ◽  
Intracellular Oxidative Stress ◽  
Iron Regulatory Protein 1

ENO1 suppresses cancer cell ferroptosis by degrading the mRNA of iron regulatory protein 1

2020 ◽  
Author(s):  
Huafeng Zhang ◽  
Tong Zhang ◽  
Linchong Sun ◽  
Yijie Hao ◽  
Wenhao Ma ◽  
...  
Keyword(s):  
Iron Homeostasis ◽  
Rna Binding ◽  
Clinical Sample ◽  
Regulatory Protein ◽  
Iron Regulatory Protein ◽  
Aberrant Expression ◽  
Hcc Cells ◽  
Iron Regulatory Protein 1

Abstract α-Enolase 1 (ENO1) is a critical glycolytic enzyme whose aberrant expression drives the pathogenesis of various cancers. ENO1 has been indicated to have additional roles beyond its conventional metabolic activity, but the underlying mechanisms and biological consequences remain elusive. Here, we show that ENO1 suppresses iron regulatory protein 1 (IRP1) expression to regulate iron homeostasis and survival of hepatocellular carcinoma (HCC) cells. Mechanistically, we unprecedentedly uncover that ENO1, as an RNA-binding protein, recruits CNOT6 to accelerate the mRNA decay of IRP1 in cancer cells, leading to inhibition of mtioferin-1 (Mfrn1) expression and subsequent repression of mitochondrial iron-induced ferroptosis. Moreover, through in vitro and in vivo experiments and clinical sample analysis, we identified IRP1 and Mfrn1 as tumor suppressors by inducing ferroptosis in HCC cells. Taken together, this study establishes a novel role for the ENO1/IRP1/Mfrn1 pathway in the pathogenesis of HCC and reveals a previously unknown connection between the ENO1/IRP1/Mfrn1 pathway and ferroptosis, suggesting a potential innovative cancer therapy.

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