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Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Iron-responsive elements (IREs) are stemloop structures found in the mRNAs encoding ferritin and the transferrin receptor. These elements participate in the iron-induced regulation of the translation of ferritin and the stability of the transferrin receptor mRNA. Regulation in both instances is mediated by binding of a cytosolic protein to the IREs. High-affinity binding is seen when cells are starved of iron and results in repression of ferritin translation and inhibition of transferrin receptor mRNA degradation. The IRE-binding protein (IRE-BP) has been identified as an approximately 90-kDa protein that has been purified by both affinity and conventional chromatography. In this report we use RNA affinity chromatography and two-dimensional gel electrophoresis to isolate the IRE-BP for protein sequencing. A degenerate oligonucleotide probe derived from a single peptide sequence was used to isolate a cDNA clone that encodes a protein containing 13 other sequenced peptides obtained from the IRE-BP. Consistent with previous characterization of the IRE-BP, the cDNA encodes a protein of 87 kDa with a slightly acidic pI, and the corresponding mRNA of approximately 3.6 kilobases is found in a variety of cell types. The encoded protein contains a nucleotide-binding consensus sequence and regions of cysteine and histidine clusters. This mRNA is encoded by a single gene on human chromosome 9, a finding consistent with previous localization by functional mapping. The protein contains no previously defined consensus motifs for either RNA or DNA binding. The simultaneous cloning of a different, but highly homologous, cDNA suggests that the IRE-BP is a member of a distinct gene family.
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PMID:Cloning of the cDNA encoding an RNA regulatory protein--the human iron-responsive element-binding protein. 217 68

Nitric oxide (NO) synthesis by cytotoxic activated macrophages has been postulated to result in a progressive loss of iron from tumor target cells as well as inhibition of mitochondrial respiration and DNA synthesis. In the present study, the addition of an NO-generating agent, sodium nitroprusside, to the iron storage protein ferritin resulted in the release of iron from ferritin and the released iron-catalyzed lipid peroxidation. Hemoglobin, which binds NO, and superoxide anion, which reacts with NO, inhibited nitroprusside-dependent iron release from ferritin, thereby providing evidence that NO can mobilize iron from ferritin. These results suggest that NO generation in vivo could lead to the mobilization of iron from ferritin disrupting intracellular iron homeostasis and increasing the level of reactive oxygen species.
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PMID:Nitric oxide mediates iron release from ferritin. 217 32

This review has considered what is known about the precise chemical mechanisms involved in the signal transduction of heavy metal ions. By reviewing what is known about general modes of signal transduction, we may draw parallels with the detection of and response to metal ions. In all forms of signal transduction, sensors and transducers are required. Yet, it is apparent that each system has unique features which undoubtedly are critical for the specific signal at hand. Within the context of metal-responsive systems, regardless of whether or not the metal ion is being sequestered, directly utilized, removed or otherwise, several examples of specific metalloregulatory proteins have been elucidated and are summarized in Table II. A close inspection of Table II reveals that in most signal transduction pathways for heavy metals, the presence of the metal ion causes a marked change in the nucleic acid binding capacity of the metalloregulatory protein. For example, the presence of iron results in the dissociation of a protein from iron responsive elements, thereby derepressing ferritin translation. In other instances, metal binding allows a metalloregulatory protein to associate with DNA to activate or repress transcription, as with ACE1 and Fur, respectively. In fact, to the authors' knowledge, it appears that all characterized ligand-responsive transcription factors change nucleic acid binding activity upon ligand binding. This change in affinity is a major feature of the mechanism for activation or repression by these receptors. In contrast, the mercuric ion metalloregulatory protein, MerR, operates by an entirely different transduction mechanism. MerR remains bound to its operator sequence in the presence and absence of mercuric ion, with only a slight increase in the dissociation rate constant in the presence of Hg(II). Furthermore, the site of MerR binding to the DNA is in a novel position for a prokaryotic activator, directly between the two sets of recognition sequences for RNA polymerase. Analysis of the protein-DNA interactions and transcriptional activity has demonstrated that MerR forms a complex with RNA polymerase in the absence of Hg(II) that is unstable and transcriptionally repressed. When Hg(II) is present in greater than nanomolar concentrations, a highly active transcription complex is formed at PT and a distortion at the center of the palindromic MerR binding site is detectable. Kinetic analysis has determined that, although no change in the binding of RNAP to PT is apparent, the presence of Hg(II) stimulates the rate of isomerization from the closed to the open transcription complex.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Metalloregulatory proteins and molecular mechanisms of heavy metal signal transduction. 220 24

A map of local curvature of the pBR322 DNA has been established by electron microscopy analysis of linearized plasmid molecules. To determine their polarity these molecules are one end labelled with an avidin-ferritin-biotin complex and the images are digitized. Local curvature is calculated from two mathematical treatments of the DNA trajectory and expressed in term of a mean dinucleotide wedge angle. Eight regions of curvature are distinguished. The four main regions of curvature have a high content of phased AA runs. The experimental curvature map is compared to theoretical maps of curvature obtained from four available models for DNA curvature.
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PMID:Electron microscopy mapping of pBR322 DNA curvature. Comparison with theoretical models. 232 39

The ferritin concentration in peripheral blood lymphocyte extracts was measured in 10 normal subjects, 7 patients with homozygous beta-thalassaemia, and 5 patients with iron-deficiency anaemia. The mean intracellular ferritin content was found increased in beta-thalassaemia and reduced in iron-deficient patients. Incubation of mononuclear cells in phytohaemagglutinin medium led to an increase of DNA synthesis concomitant with an increased number of lymphocytes bearing transferrin receptor and interleukin-2 receptor as measured by immunofluorescent technique. Although there was an immunological impairment of lymphocytes in patients with either iron depletion or iron loading compared to normal subjects, their ability to express transferrin receptor and interleukin-2 receptor on their cell surface was normal.
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PMID:Expression of cell-surface transferrin receptor following in vitro stimulation of peripheral blood lymphocytes in patients with beta-thalassaemia and iron-deficiency anaemia. 232 91

Pleuropneumonia is an important disease of swine caused by Actinobacillus pleuropneumoniae. Putative virulence determinants include capsule, lipopolysaccharide, and cytotoxin. We studied the virulence and virulence determinants of 2 strains: CM5 and CM5A of serotype 1. Strain CM5 was isolated from a pig with pleuropneumonia and passaged once in vitro; strain CM5A was a substrain of CM5 passaged 70 times in vitro. Pigs challenge exposed to an aerosol of 1.3 x 10(7) colony-forming units of CM5/ml died within 30 hours; pigs challenge exposed to an aerosol of 1.6 x 10(8) colony-forming units of CM5A/ml survived. The average thickness of the capsular layer was 137 nm in strain CM5 and 53 nm in strain CM5A in bacteria treated with homologous antibody and examined by transmission electron microscopy. Similarly, capsular material binding polycationic ferritin was found in colonies of strain CM5, but not in strain CM5A. The ratio of hexosamine to protein in extracted capsule of CM5 was more than twice that of CM5A. The polyacrylamide gel electrophoretic profile of the lipopolysaccharide, outer membrane proteins, and whole cell proteins did not differ between the 2 strains. Also, the amount of cytotoxin or endotoxin produced by the 2 strains during the logarithmic growth phase was not different. The electrophoretic profile of restriction endonuclease digested DNA was similar, with the exception of bands in the 750- and 620-basepair regions. It was concluded that attenuation of strain CM5A during in vitro passage was a result of reduced capsule production and that encapsulation is an important virulence determinant of A pleuropneumoniae, serotype 1.
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PMID:Characterization of an attenuated strain of Actinobacillus pleuropneumoniae, serotype 1. 233 67

A method for the separation of complementary strands with the help of the biotin-avidin system is described. Restriction fragments were terminally labeled at both ends with biotinylated nucleotides. The DNA was cut by a second restriction enzyme, and the fragments were bound to an avidin agarose column. The non-biotinylated strands were eluted with 0.1 M NaOH, and the biotin-labeled strands were subsequently released from the column by elution with 50% guanidine isothiocyanate/formamide. Contamination of the separated strands by complementary single strands was less than 4%.-Separated linear single strands of the vector pEMBL were prepared. On annealing with recombinant circular DNA a substitution loop is formed which provides position and orientation markers for the unambiguous electron microscopic analysis of heteroduplexes or hybrids formed with the inserted sequences. -The terminal biotin label was visualized by complex formation with a streptavidin-ferritin conjugate.
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PMID:Separation of complementary strands of plasmid DNA using the biotin-avidin system and its application to heteroduplex formation and RNA/DNA hybridizations in electron microscopy. 241 6

Incubation of HeLa cells for 24 h with either hydroxyurea (HU), aphidicolin (APHI), thymidine (T) or butyrate (BU), substances used to inhibit replication and accumulate cells at the G1/S interphase, followed by the elimination of the inhibitor and the addition of iron to the growth medium, results in an immediate (HU, APHI, T) or slightly delayed (BU) increased accumulation (18-24-fold higher than the basal level) of ferritin. Under the same experimental circumstances, 5-azacytidine is without effect. As a result of the action of these inhibitors on the structure of DNA, it is proposed that ferritin genes remain accessible to RNA polymerase allowing the accumulation in the cytoplasm of mature ferritin mRNA ready to be mobilized by iron for the production of ferritin molecules.
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PMID:Stimulation of protein accumulation in HeLa cells by inhibitors of DNA replication. Ferritin. 241 93

Ferritin synthesis provides a dramatic example of translational control; stored ferritin mRNA is translated at relatively low rates which can increase 40-50 times when cellular iron levels increase. Although it is not known if agents other than cellular iron levels can release the repression of ferritin mRNA in vivo, the repression appears to be eliminated during the isolation of poly(A+) RNA, judged by translation in wheat germ lysates (WG). Using the bullfrog tadpole as a model, because of the abundance of ferritin-rich embryonic red cells, we now show specific repression of ferritin mRNA in the isolated poly(A+) RNA translated in rabbit reticulocyte lysates (RR) (RR/WG = 25%). Repression of ferritin mRNA was associated with the inability to form polyribosomes in analogy to iron-poor cells in vivo. The addition of various complexes of iron did not relieve the repression, suggesting that in vivo at least part of the effect of iron may be indirect and mediated by factors absent in the cell-free system; all three ferritin subunit mRNAs (H, M, and L) appeared to be regulated coordinately in vitro and in vivo as well. Comparison of transcripts of DNA encoding the M subunit of ferritin, but containing deletions in the 3'-untranslated (UT) region, showed that a region 70 nucleotides long was important for repression. Comparison of secondary structures predicted for the eight known ferritin subunit mRNAs from humans, rats, chickens, and frogs indicates that a region involved in base pairing common to all the mRNAs is eliminated when the 3'-UT region is shortened to 24 nucleotides. Although regions in the 5'-UT of mRNAs, including ferritin, have been shown to be involved in translational regulation, it is clear that complete regulation can involve both the 3'-UT and the 5'-UT regions, mediated, presumably, by secondary and tertiary interactions along the mRNA molecule.
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PMID:The importance of the 3'-untranslated region in the translational control of ferritin mRNA. 244 37

The biosynthetic rates for both the transferrin receptor (TfR) and ferritin are regulated by iron. An iron-responsive element (IRE) in the 5' untranslated portion of the ferritin messenger RNA (mRNA) mediates iron-dependent control of its translation. In this report the 3' untranslated region of the mRNA for the human TfR was shown to be necessary and sufficient for iron-dependent control of mRNA levels. Deletion studies identified a 678-nucleotide fragment of the TfR complementary DNA that is critical for this iron regulation. Five potential stem-loops that resemble the ferritin IRE are contained within the region critical for TfR regulation. Each of two of the five TfR elements was independently inserted into the 5' untranslated region of an indicator gene transcript. In this location they conferred iron regulation of translation. Thus, an mRNA element has been implicated in the mediation of distinct regulatory phenomena dependent on the context of the element within the transcript.
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PMID:Iron-responsive elements: regulatory RNA sequences that control mRNA levels and translation. 245 85


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