Binding of cytosolic aconitase to the iron responsive element of porcine mitochondrial aconitase mRNA

Zheng, Limin; Kennedy, Mary Claire; Blondin, George A.; Beinert, Helmut; Zalkin, Howard

doi:10.1016/0003-9861(92)90287-7

Cited by 77 publications

(37 citation statements)

References 29 publications

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“…Hence the function of this protein depends on the availability of intracellular iron for the formation of the [Fe-S] cofactor (Klausner & Rouault, 1993). Crystallographic structure analysis and mutational analysis have led to the identification of 23 residues contributing to the active site (Lauble et al, 1992;Zheng et al, 1992). The 23 residues, which are involved in substrate recognition, [Fe-S] cluster ligation and interaction, catalysis or hydrogen binding that support the active-site side chains are also present in the M. avium AcnA sequence (data not shown).…”

Section: Aconitasementioning

confidence: 99%

Determination of a 15437 bp nucleotide sequence around the inhA gene of Mycobacterium avium and similarity analysis of the products of putative ORFs

et al. 1998

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A 15437 bp region encompassing the inhA locus from the Mycobacterium awium chromosome was cloned and sequenced. From the sequencing data generated and the results of homology searches, the primary structure of this region was determined. This region contains four known genes (acnA, fabG, inhA and hemH) and two genes, inwA and inwB, whose products display homology with p60 invasion protein of Listeria monocytogenes. Six proteins encoded by putative ORFs contained an RGD motif (often involved in binding to macrophage integrins), while ORFl and MoxR are probably transcriptional regulators. The rest of the putative products encoded by ORFs in the sequenced region showed little homology with the proteins contained in the databases and were considered to be unknown proteins.

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Section: Aconitasementioning

confidence: 99%

Determination of a 15437 bp nucleotide sequence around the inhA gene of Mycobacterium avium and similarity analysis of the products of putative ORFs

et al. 1998

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“…Iron-regulatory proteins 1 and 2 (IRP-1 and IRP-2) are cytoplasmic proteins known to interact with specific nucleotide sequences, called iron-responsive elements (IREs), which are located in the 3Ј-untranslated region (UTR) of TfR mRNA (1, 2, 7) as well as the 5Ј-UTRs of mRNAs for ferritin (1,2,8), erythroid-specific 5-aminolevulinic acid synthase (9), and mitochondrial aconitase (10). When cellular iron becomes limiting, the IRP-1 is recruited into the high affinity binding state.…”

mentioning

confidence: 99%

Control of Transferrin Receptor Expression via Nitric Oxide-mediated Modulation of Iron-regulatory Protein 2

Kim

Ponka

1999

Journal of Biological Chemistry

107

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“…The iron-induced decrease in IRP-1 binding activity occurs through a switch between apoprotein (high affinity) and [4Fe-4S] forms (low affinity) without changes in IRP-1 levels (18), whereas the decrease in IRP-2 binding activity is due to iron-induced IRP-2 proteolysis (19,20). IREs are also present on the 5Ј-untranslated regions of erythroid 5-aminolevulinate synthase (21) and mitochondrial aconitase (22) and on mitochondrial succinate dehydrogenase subunit b in Drosophila melanogaster (23). In addition to iron, nitric oxide (24 -26), oxidative stress (27,28), and ascorbic acid (29) have also been shown to regulate IRP binding to the IREs (reviewed in Ref.…”

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confidence: 99%

Resistance to the Antitumor Agent Gallium Nitrate in Human Leukemic Cells Is Associated with Decreased Gallium/Iron Uptake, Increased Activity of Iron Regulatory Protein-1, and Decreased Ferritin Production

Chitambar

Wereley

1997

Journal of Biological Chemistry

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The mechanism of drug resistance to gallium nitrate is not known. Since gallium can be incorporated into ferritin, an iron storage protein that protects cells from iron toxicity, we investigated whether ferritin expression was altered in gallium-resistant (R) CCRF-CEM cells. We found that the ferritin content of R cells was decreased, while heavy chain ferritin mRNA levels and iron regulatory protein-1 (IRP-1) RNA binding activity were increased. IRP-1 protein levels were similar in gallium-sensitive (S) and R cells, indicating that R cells contain a greater proportion of IRP-1 in a high affinity mRNA binding state. 59 Fe uptake and transferrin receptor expression were decreased in R cells. In both S and R cells, gallium inhibited cellular 59 Fe uptake, increased ferritin mRNA and protein, and decreased IRP-1 binding activity. Gallium uptake by R cells was markedly diminished; however, the sensitivity of R cells to gallium could be restored by increasing their uptake of gallium with excess transferrin. Our results suggest that R cells have developed resistance to gallium by down-regulating their uptake of gallium. In parallel, iron uptake by R cells is also decreased, leading to changes in iron homeostasis. Furthermore, since gallium has divergent effects on iron uptake and ferritin synthesis, its action may also include a direct effect on ferritin mRNA induction and IRP-1 activity.Gallium nitrate, a group IIIa metal salt with antineoplastic activity (1), is currently undergoing evaluation as a chemotherapeutic agent. A number of clinical studies have shown gallium to be effective in the treatment of lymphoma and bladder cancer (2-4). Although gallium is in clinical use, information regarding its action at the cellular and molecular levels is largely incomplete. It has been known for some time that gallium resembles iron in certain respects. Gallium binds avidly to the iron transport protein Tf 1 (5) and is incorporated into cells by Tf receptor-dependent and -independent transport systems (6 -8). Furthermore, we have shown that gallium inhibits the growth of several leukemic cell lines by inhibiting cellular iron uptake and by blocking the activity of ribonucleotide reductase (9 -11).Iron taken up by cells is stored in ferritin, a high molecular weight protein composed of 24 subunits of H and L chains (12). Ferritin sequesters excess intracellular iron and protects cells from the toxicity of iron overload. An increase in the delivery of iron to cells therefore serves as a powerful stimulus for ferritin synthesis. It is now established that iron-dependent ferritin and transferrin receptor gene expression is regulated by the binding of two iron regulatory proteins (IRPs), IRP-1 and IRP-2, to sequences termed iron-responsive elements (IREs) present at the 5Ј-untranslated region of ferritin mRNA and the 3Ј-untranslated region of Tf receptor mRNA (13-17). In irondepleted cells, IRPs bind with high affinity to the IREs, resulting in suppression of ferritin mRNA translation and stabilization of Tf receptor mRNA (incr...

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Binding of cytosolic aconitase to the iron responsive element of porcine mitochondrial aconitase mRNA

Cited by 77 publications

References 29 publications

Determination of a 15437 bp nucleotide sequence around the inhA gene of Mycobacterium avium and similarity analysis of the products of putative ORFs

Determination of a 15437 bp nucleotide sequence around the inhA gene of Mycobacterium avium and similarity analysis of the products of putative ORFs

Control of Transferrin Receptor Expression via Nitric Oxide-mediated Modulation of Iron-regulatory Protein 2

Resistance to the Antitumor Agent Gallium Nitrate in Human Leukemic Cells Is Associated with Decreased Gallium/Iron Uptake, Increased Activity of Iron Regulatory Protein-1, and Decreased Ferritin Production

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