Iron regulatory factor

Dtapier, J. C., Hirling, H., Wietzerbin, J., Kaldy, P., and Kuhn, L. C. (1993). Biosynthesis of nitric oxide activates iron regulatory factor in macrophages. EMBO J. 12, 3643-3649. 

Aconitase exists as both mitochondrial and cytosolic isoenzyme forms of similar structure. However, the cytosolic isoenzyme has a second function. In its apoenzyme form, which lacks the iron-sulfur cluster, it acts as the much-studied iron regulatory factor, or iron-responsive element binding protein (IRE-BP). This protein binds to a specific stem-loop structure in the messenger RNA for proteins involved in iron transport and storage (Chapter 28).86/9°... 

SELEX has also allowed the characterization of the RNA hairpin, which constitutes the iron responsive element (IRE) recognized by the iron regulatory factor (IRF) protein to post-transcriptionally regulate translatability and decay of mRNAs involved in iron import and storage in eukaryotic cells (Henderson et al., 1994). 

Henderson, B.R., Menotti, E., Bonnard, C. and Kuhn, L.C. (1994) Optimal sequence and structure of iron-responsive elements. Selection of RNA stem-loops with high affinity for iron regulatory factor. J. Biol. Chem., 269, 17481-17489. 

Melefors, 6., Hentze, M.W. Iron regulatory factor - the conductor of cellular iron regulation. Blood Rev. 1993 7 251-258... 

The IRE-binding activity was first monitored in rat cytoplasmic extracts by an electrophoretic mobility shift assay [40]. Soon thereafter, this activity was detected in most tissues and cell lines examined, and reported in the literature with various confusing names IRE-binding protein (IRE-BP) [79], iron regulatory factor ... 

NO produced by the cells upon cytokine induction, or added as a gas to the recombinant protein, converts the iron-regulatory protein (also called iron-regulatory factor [IRF] or iron-responsive element-binding protein [IRE-BP]) to the same condition as low iron, causing a binding of the protein to mRNA (Drapier et al. 1993, Weiss et al. 1993). 

Beinert H, Kennedy MC. Aconitase, a two-faced protein enzyme and iron regulatory factor. FASEB J 1993 7 1442-1449. 

In the EPR of mammalian cells, we do not see much in addition to the signals from the respiratory complexes. The enzyme aconitase from the citric-acid cycle can be detected, and also the protein cytoplasmic aconitase, later identified as the mRNA translation regulatory factor iron regulatory protein IRP-1, which actually started its career in biochemistry as an EPR signal that could not be assigned to the respiratory chain (Kennedy et al. 1992). 

Relatively recently Fe/S proteins have been found to function in the regulation of biosynthesis. This can be by promoting deoxyribonucleic acid (DNA) transcription, e.g. the [2Fe-2S] containing Escherichia coli superoxide-activated (SoxR) transcription activator [10-12], or the presumably [4Fe-4S]-containing E. coli transcription factor fumarate nitrate reduction (FNR) [13,14], Alternatively, the Fe/S protein can act by interference with messenger ribonucleic acid (mRNA) translation, i.e., the iron regulatory proteins (IRPs) [15,16], These interactions are stoichiometric, therefore not catalytic. Presumably, they are also a form of sensoring, namely, of oxidants and/or iron [17],... 

NO-uptake and photorelease as regulatory factors (48). Prominent model nonheme iron-nitrosylated species are SNP (8,9), diverse types of dinitrosyls (49), and sulfur clusters (such as Roussin s salts) (49,50), as well as NHase-mimics (51,52). Structural advances have been achieved for the heme-nitrosyl compounds during the last decade (18,53). 

DMTl, divalent metal transporter Hb, hemoglobin BMP, bone morphogenetic protein GDF15, growth differentiation factor 15 IRP, iron regulatory protein. 

Thomson, A.M., J.T. Rogers, and P.J. Leedman, Thyrotropin-releasing hormone and epidermal growth factor regulate iron- regulatory protein binding in pituitary cells via protein kinase C- dependent and -independent signaling pathways [In Process Citation], J Biol Chem, 2000.275(41) p. 31609-15. 

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