scholarly journals Hypoxia Alters Iron-regulatory Protein-1 Binding Capacity and Modulates Cellular Iron Homeostasis in Human Hepatoma and Erythroleukemia Cells

1999 ◽  
Vol 274 (7) ◽  
pp. 4467-4473 ◽  
Author(s):  
Ildiko Toth ◽  
Liping Yuan ◽  
Jack T. Rogers ◽  
Hayden Boyce ◽  
Kenneth R. Bridges
Keyword(s):  
Iron Homeostasis ◽  
Binding Capacity ◽  
Regulatory Protein ◽  
Iron Regulatory Protein ◽  
Human Hepatoma ◽  
Cellular Iron ◽  
Erythroleukemia Cells ◽  
Cellular Iron Homeostasis ◽  
Iron Regulatory Protein 1

scholarly journals Iron regulatory protein 1 promotes ferroptosis by sustaining cellular iron homeostasis in melanoma

2021 ◽  
Vol 22 (3) ◽  
Author(s):  
Fengping Yao ◽  
Xiaohong Cui ◽  
Ying Zhang ◽  
Zhuchun Bei ◽  
Hongquan Wang ◽  
...  
Keyword(s):  
Iron Homeostasis ◽  
Regulatory Protein ◽  
Iron Regulatory Protein ◽  
Cellular Iron ◽  
Cellular Iron Homeostasis ◽  
Iron Regulatory Protein 1

scholarly journals Chlamydia trachomatisAlters Iron-Regulatory Protein-1 Binding Capacity and Modulates Cellular Iron Homeostasis in HeLa-229 Cells

2009 ◽  
Vol 2009 ◽  
pp. 1-7 ◽  
Author(s):  
Harsh Vardhan ◽  
Apurb R. Bhengraj ◽  
Rajneesh Jha ◽  
Aruna Singh Mittal
Keyword(s):  
Iron Homeostasis ◽  
Binding Capacity ◽  
Regulatory Protein ◽  
Binding Activity ◽  
Iron Regulatory Protein ◽  
Mobility Shift ◽  
Cellular Iron ◽  
Infected Cells ◽  
Mobility Shift Assay ◽  
Cellular Iron Homeostasis

Chlamydia trachomatis(CT) is the leading cause of diseases related to reproductive health and iron plays important role in chlamydial pathogenesis. Iron homeostasis in chlamydia-infected cells is not clear thus far. This study shows that expression of the transferrin receptor (TfR) is downregulated, whereas expression of the ferritin heavy chain is upregulated in CT-infected HeLa-229 cells. Expression of iron-regulatory protein (IRP)-1 predominates over IRP-2 in infected cells. In infected cells, attenuated binding activity of IRP-iron responsive elements (IREs) is observed using the electrophoretic mobility-shift assay. These results suggest that iron homeostasis is modulated in CT-infected HeLa cells at the interface of acquisition and commensal use of iron.

scholarly journals Iron Regulatory Protein 1 Outcompetes Iron Regulatory Protein 2 in Regulating Cellular Iron Homeostasis in Response to Nitric Oxide

2011 ◽  
Vol 286 (26) ◽  
pp. 22846-22854 ◽  
Author(s):  
Agnieszka Styś ◽  
Bruno Galy ◽  
Rafal R. Starzyński ◽  
Ewa Smuda ◽  
Jean-Claude Drapier ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Iron Homeostasis ◽  
Regulatory Protein ◽  
Iron Regulatory Protein ◽  
Cellular Iron ◽  
Cellular Iron Homeostasis ◽  
Iron Regulatory Protein 1

scholarly journals Glycogen branching enzyme controls cellular iron homeostasis via Iron Regulatory Protein 1 and mitoNEET

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Nhan Huynh ◽  
Qiuxiang Ou ◽  
Pendleton Cox ◽  
Roland Lill ◽  
Kirst King-Jones
Keyword(s):  
Iron Homeostasis ◽  
Nuclear Translocation ◽  
Regulatory Protein ◽  
Glycogen Metabolism ◽  
Glycogen Storage Disease Type ◽  
Iron Regulatory Protein ◽  
Messenger Rnas ◽  
Branching Enzyme ◽  
Cellular Iron ◽  
Iron Regulatory Protein 1

AbstractIron Regulatory Protein 1 (IRP1) is a bifunctional cytosolic iron sensor. When iron levels are normal, IRP1 harbours an iron-sulphur cluster (holo-IRP1), an enzyme with aconitase activity. When iron levels fall, IRP1 loses the cluster (apo-IRP1) and binds to iron-responsive elements (IREs) in messenger RNAs (mRNAs) encoding proteins involved in cellular iron uptake, distribution, and storage. Here we show that mutations in the Drosophila 1,4-Alpha-Glucan Branching Enzyme (AGBE) gene cause porphyria. AGBE was hitherto only linked to glycogen metabolism and a fatal human disorder known as glycogen storage disease type IV. AGBE binds specifically to holo-IRP1 and to mitoNEET, a protein capable of repairing IRP1 iron-sulphur clusters. This interaction ensures nuclear translocation of holo-IRP1 and downregulation of iron-dependent processes, demonstrating that holo-IRP1 functions not just as an aconitase, but throttles target gene expression in anticipation of declining iron requirements.

scholarly journals Involvement of the Iron Regulatory Protein from Eisenia andrei Earthworms in the Regulation of Cellular Iron Homeostasis

PLoS ONE ◽  
2014 ◽  
Vol 9 (10) ◽  
pp. e109900
Author(s):  
Petra Procházková ◽  
František Škanta ◽  
Radka Roubalová ◽  
Marcela Šilerová ◽  
Jiří Dvořák ◽  
...  
Keyword(s):  
Iron Homeostasis ◽  
Regulatory Protein ◽  
Iron Regulatory Protein ◽  
Eisenia Andrei ◽  
Cellular Iron ◽  
Cellular Iron Homeostasis

scholarly journals Function and crystal structure of the dimeric P-loop ATPase CFD1 coordinating an exposed [4Fe-4S] cluster for transfer to apoproteins

2018 ◽  
Vol 115 (39) ◽  
pp. E9085-E9094 ◽  
Author(s):  
Oliver Stehling ◽  
Jae-Hun Jeoung ◽  
Sven A. Freibert ◽  
Viktoria D. Paul ◽  
Sebastian Bänfer ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Iron Homeostasis ◽  
De Novo ◽  
Regulatory Protein ◽  
Protein Translation ◽  
Cluster Assembly ◽  
Cellular Iron ◽  
Chaetomium Thermophilum ◽  
Cellular Iron Homeostasis ◽  
S Proteins

Maturation of iron-sulfur (Fe-S) proteins in eukaryotes requires complex machineries in mitochondria and cytosol. Initially, Fe-S clusters are assembled on dedicated scaffold proteins and then are trafficked to target apoproteins. Within the cytosolic Fe-S protein assembly (CIA) machinery, the conserved P-loop nucleoside triphosphatase Nbp35 performs a scaffold function. In yeast, Nbp35 cooperates with the related Cfd1, which is evolutionary less conserved and is absent in plants. Here, we investigated the potential scaffold function of human CFD1 (NUBP2) in CFD1-depleted HeLa cells by measuring Fe-S enzyme activities or 55Fe incorporation into Fe-S target proteins. We show that CFD1, in complex with NBP35 (NUBP1), performs a crucial role in the maturation of all tested cytosolic and nuclear Fe-S proteins, including essential ones involved in protein translation and DNA maintenance. CFD1 also matures iron regulatory protein 1 and thus is critical for cellular iron homeostasis. To better understand the scaffold function of CFD1-NBP35, we resolved the crystal structure of Chaetomium thermophilum holo-Cfd1 (ctCfd1) at 2.6-Å resolution as a model Cfd1 protein. Importantly, two ctCfd1 monomers coordinate a bridging [4Fe-4S] cluster via two conserved cysteine residues. The surface-exposed topology of the cluster is ideally suited for both de novo assembly and facile transfer to Fe-S apoproteins mediated by other CIA factors. ctCfd1 specifically interacted with ATP, which presumably associates with a pocket near the Cfd1 dimer interface formed by the conserved Walker motif. In contrast, ctNbp35 preferentially bound GTP, implying differential regulation of the two fungal scaffold components during Fe-S cluster assembly and/or release.

Nickel decreases cellular iron level and converts cytosolic aconitase to iron-regulatory protein 1 in A549 cells

2005 ◽  
Vol 206 (3) ◽  
pp. 275-287 ◽  
Author(s):  
Haobin Chen ◽  
Todd Davidson ◽  
Steven Singleton ◽  
Michael D. Garrick ◽  
Max Costa
Keyword(s):  
Regulatory Protein ◽  
A549 Cells ◽  
Iron Level ◽  
Iron Regulatory Protein ◽  
Cellular Iron ◽  
Iron Regulatory Protein 1

Interaction of iron regulatory protein-1 (IRP-1) with ATP/ADP maintains a non-IRE-binding state

2010 ◽  
Vol 430 (2) ◽  
pp. 315-324 ◽  
Author(s):  
Zvezdana Popovic ◽  
Douglas M. Templeton
Keyword(s):  
Atpase Activity ◽  
Atp Hydrolysis ◽  
Binding Capacity ◽  
Regulatory Protein ◽  
Product Formation ◽  
Binding Activity ◽  
Hill Coefficient ◽  
Iron Regulatory Protein ◽  
Aconitase Activity ◽  
Iron Regulatory Protein 1

In its aconitase-inactive form, IRP-1 (iron regulatory protein-1)/cytosolic aconitase binds to the IRE (iron-responsive element) of several mRNAs to effect post-transcriptional regulation. We have shown previously that IRP-1 has ATPase activity and that binding of ATP suppresses the IRP-1/IRE interaction. In the present study, we characterize the binding activity further. Binding is observed with both [α-32P]ATP and [α-32P]ADP, but not with [γ-32P]ATP. Recombinant IRP-1 binds approximately two molecules of ATP, and positive co-operativity is observed with a Hill coefficient of 1.67±0.36 (EC50=44 μM) commencing at 1 μM ATP. Similar characteristics are observed with both apoprotein and the aconitase form. On binding, ATP is hydrolysed to ADP, and similar binding parameters and co-operativity are seen with ADP, suggesting that ATP hydrolysis is not rate limiting in product formation. The non-hydrolysable analogue AMP-PNP (adenosine 5′-[β,γ-imido]triphosphate) does not induce co-operativity. Upon incubation of IRP-1 with increasing concentrations of ATP or ADP, the protein migrates more slowly on agarose gel electrophoresis, and there is a shift in the CD spectrum. In this new state, adenosine nucleotide binding is competed for by other nucleotides (CTP, GTP and AMP-PNP), although ATP and ADP, but not the other nucleotides, partially stabilize the protein against spontaneous loss of aconitase activity when incubated at 37 °C. A mutant IRP-1(C437S) lacking aconitase activity shows only one ATP-binding site and lacks co-operativity. It has increased IRE-binding capacity and lower ATPase activity (Km=75±17 nmol/min per mg of protein) compared with the wild-type protein (Km=147±48 nmol/min per mg of protein). Under normal cellular conditions, it is predicted that ATP/ADP will maintain IRP-1 in a non-IRE-binding state.

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