Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.25.1 (proteasome)
 28,817 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In duck erythroblasts, two major populations of untranslated messenger (m) RNP can be separated by sucrose gradient centrifugation in low ionic strength. One of these contains globin mRNA associated to protein factors, among them the prosomes. The other, sedimenting in the 35S zone, contains non-globin mRNA. From this '35S' mRNP, a new RNP particle called the prosome-like particle was isolated and characterized [Akhayat, O., Infante, A. A., Infante, D., Martins de Sa, C., Grossi de Sa, M.-F. & Scherrer, K. (1987) Eur. J. Biochem. 170, 23-33]. The PLP is a multimer of a protein of M(r) 21,000, and contains small RNA species. The particle is tightly associated with repressed mRNA and inhibits in vitro protein synthesis. We show here that the protein of M(r) 21,000, constituting the prosome-like particle, is apoferritin. Different approaches confirm the RNP character of this particle and provide evidence that some of its RNA species are tRNA. The hypothesis is discussed as to whether (apo-)ferritin might serve other functions in addition to iron storage.
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PMID:The protein of M(r) 21,000 constituting the prosome-like particle of duck erythroblasts is homologous to apoferritin. 149 59

In vivo most extracellular iron is bound to transferrin or lactoferrin in such a way as to be unable to catalyze the formation of hydroxyl radical from superoxide (.O2-) and hydrogen peroxide (H2O2). At sites of Pseudomonas aeruginosa infection bacterial and neutrophil products could possibly modify transferrin and/or lactoferrin forming catalytic iron complexes. To examine this possibility, diferrictransferrin and diferriclactoferrin which had been incubated with pseudomonas elastase, pseudomonas alkaline protease, human neutrophil elastase, trypsin, or the myeloperoxidase product HOCl were added to a hypoxanthine/xanthine oxidase .O2-/H2O2 generating system. Hydroxyl radical formation was only detected with pseudomonas elastase treated diferrictransferrin and, to a much lesser extent, diferriclactoferrin. This effect was enhanced by the combination of pseudomonas elastase with other proteases, most prominently neutrophil elastase. Addition of pseudomonas elastase-treated diferrictransferrin to stimulated neutrophils also resulted in hydroxyl radical generation. Incubation of pseudomonas elastase with transferrin which had been selectively iron loaded at either the NH2- or COOH-terminal binding site yielded iron chelates with similar efficacy for hydroxyl radical catalysis. Pseudomonas elastase and HOCl treatment also decreased the ability of apotransferrin to inhibit hydroxyl radical formation by a Fe-NTA supplemented hypoxanthine/xanthine oxidase system. However, apotransferrin could be protected from the effects of HOCl if bicarbonate anion was present during the incubation. Apolactoferrin inhibition of hydroxyl radical generation was unaffected by any of the four proteases or HOCl. Alteration of transferrin by enzymes and oxidants present at sites of pseudomonas and other bacterial infections may increase the potential for local hydroxyl radical generation thereby contributing to tissue injury.
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PMID:Pseudomonas and neutrophil products modify transferrin and lactoferrin to create conditions that favor hydroxyl radical formation. 165 25

The Pseudomonas aeruginosa siderophore pyoverdin was unable to acquire iron from human transferrin or lactoferrin at physiological pH. However, in the presence of P. aeruginosa elastase, rapid iron release and pyoverdin iron uptake from transferrin but not from lactoferrin were detected. Neither P. aeruginosa alkaline protease nor elastase from polymorphonuclear leukocytes revealed this effect.
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PMID:Impact of proteases on iron uptake of Pseudomonas aeruginosa pyoverdin from transferrin and lactoferrin. 312 14

The effect of Pseudomonas aeruginosa alkaline protease (AP), elastase (Ela), and the elastase from polymorphonuclear leukocytes (PMN Ela) on iron acquisition of pyoverdin from human transferrin and lactoferrin at physiologic pH was investigated. Incubation of iron-loaded transferrin with iron-free pyoverdin for 10 h at 40 degrees C in the presence of Ela yielded pyoverdin-iron(III) complex, in contrast to incubations of transferrin with pyoverdin alone, AP, or PMN Ela. Sodium dodecyl sulfate polyacrylamide gel electrophoresis analysis of the incubations revealed fragmentation of transferrin by Ela in peptides smaller than 14,000 daltons, whereas AP and PMN Ela cleaved transferrin in fragments of 49,000 d and 43,000 d, respectively. Incubations of lactoferrin with the proteases and pyoverdin or pyoverdin alone did not result in iron acquisition by pyoverdin; however, lactoferrin was fragmented by Ela and AP.
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PMID:Iron-chelating substances and inflammation. 313 54

Iron affects yields of toxin A, alkaline protease, elastase, pyochelin, and pyoverdin in Pseudomonas aeruginosa. Mutants of P. aeruginosa PAO1 resistant to the effect of iron on toxin (toxC) or elastase (elaC) yields were isolated. Two types of mutants were isolated: iron transport and iron regulatory mutants. The toxC regulatory mutants produced toxin A in medium containing iron; however, yields of elastase and alkaline protease remained sensitive to regulation by iron. The elaC regulatory mutants were resistant to the effect of iron on elastase yields, but toxin A and alkaline protease yields were decreased by iron, analogous to the parent strain. These data suggest that toxin A, elastase, and alkaline protease yields can be independently regulated by iron.
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PMID:Pseudomonas aeruginosa mutants altered in their sensitivity to the effect of iron on toxin A or elastase yields. 680 61

Iron regulatory proteins (IRPs) regulate the expression of genes involved in iron metabolism whose transcripts contain RNA stem-loop motifs known as iron-responsive elements (IREs). When iron concentrations are low, IRPs bind to IREs in the 5' untranslated region (UTR) of transcripts where they repress translation, or the 3' UTR of transcripts where they inhibit degradation. The RNA binding activities of the homologous proteins IRP1 and IRP2 are both regulated post-translationally. The binding activity of IRP2 is regulated by the degradation of the protein when cells are iron-replete. Here, we demonstrate that a 73 amino acid sequence that corresponds to a unique exon in IRP2 contains a sequence required for rapid degradation in iron-replete cells. The deletion of this sequence eliminates the rapid turnover of IRP2, whereas the transfer of this sequence to the corresponding position in the homologous protein IRP1 confers the capacity for iron-dependent degradation upon IRP1. Site-directed mutagenesis has demonstrated that specific cysteines within the IRP2 exon are required for iron-dependent degradation. The degradation of IRP2 appears to be mediated by the proteasome in iron-replete cells. When degradation is prevented, the RNA binding activity of IRP2 is not regulated by iron concentration. Thus, degradation is required for the regulation of the RNA binding activity of IRP2.
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PMID:Requirements for iron-regulated degradation of the RNA binding protein, iron regulatory protein 2. 748 24

Pseudomonas pseudomallei is the causative agent of melioidosis, a glanders-like disease of humans and animals. The pathogenesis of melioidosis is not well understood, and the role of various extracellular enzymes produced by P. pseudomallei in the development of this disease is not known. The present studies were designed to purify and characterize an extracellular protease produced by P. pseudomallei isolates and to test the hypothesis that this protease may play a role in melioidosis. The protease was present in culture supernatants as an enzyme with a molecular weight of 36,000 that was optimally active at 60 degrees C and at pH 8.0. The P. pseudomallei protease was shown to be a metalloenzyme requiring iron for maximal activity, and activity was inhibited in the presence of ethylenediaminetetraacetic acid (150 mM). Antibodies directed against an alkaline protease produced by Pseudomonas aeruginosa cross-reacted with the P. pseudomallei protease. These data indicate that the P. pseudomallei protease belongs to the family of alkaline proteases sensitive to metal chelators. Purified P. pseudomallei protease was capable of digesting a variety of eucaryotic protein substrates including immunoglobulins. A P. pseudomallei strain deficient in protease production was shown to be less virulent than the parental strain in an animal model of lung infection. These data suggest that this protease may be a significant pathogenic determinant in infections caused by P. pseudomallei.
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PMID:Purification and characterization of a protease from Pseudomonas pseudomallei. 752 33

Iron regulatory proteins (IRP1 and IRP2) are RNA-binding proteins that bind to specific structures, termed iron-responsive elements (IREs), that are located in the 5'- or 3'-untranslated regions of mRNAs that encode proteins involved in iron homeostasis. IRP1 and IRP2 RNA binding activities are regulated by iron; IRP1 and IRP2 bind IREs with high affinity in iron-depleted cells and with low affinity in iron-repleted cells. The decrease in IRP1 RNA binding activity occurs by a switch between apoprotein and 4Fe-4S forms, without changes in IRP1 levels, whereas the decrease in IRP2 RNA binding activity reflects a reduction in IRP2 levels. To determine the mechanism by which iron decreases IRP2 levels, we studied IRP2 regulation by iron in rat hepatoma and human HeLa cells. The iron-dependent decrease in IRP2 levels was not due to a decrease in the amount of IRP2 mRNA or to a decrease in the rate of IRP2 synthesis. Pulse-chase experiments demonstrated that iron resulted in a 3-fold increase in the degradation rate of IRP2. IRP2 degradation depends on protein synthesis, but not transcription, suggesting a requirement for a labile protein. IRP2 degradation is not prevented by lysosomal inhibitors or calpain II inhibitors, but is prevented by inhibitors that block proteasome function. These data suggest the involvement of the proteasome in iron-mediated IRP2 proteolysis.
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PMID:Iron regulates the intracellular degradation of iron regulatory protein 2 by the proteasome. 766 79

Thirty-six feed phosphates, including nine mono-dicalcium phosphates (M-DCP, 21% P), 13 di-monocalcium phosphates (D-MCP, 18.5% P), and 14 thermochemically produced defluorinated phosphates (DFP, 18.0% P), were analyzed for moisture, Ca, P, and 9 essential minerals (K, Mg, Na, Cl, Fe, Cu, Mn, Se, and Zn). Also, nine potentially toxic elements (Al, F, As, Cd, Cr, Hg, Pb, Ni, and V) were determined. All of the M-DCP were of domestic origin; 5 of the 13 D-MCP samples were obtained in Algeria, Peru, Holland, and South Africa. The DFP samples included 10 domestic products, 2 samples from Russia, 1 from Poland, and 1 from Japan. Levels of Na were high in the DFP samples (3.96 to 5.78%), except for the two Russian samples, which contained only .16 and .19%. Magnesium levels varied from .09 to .76%, .02 to 1.21%, and .01 to 1.54% in the M-DCP, D-MCP, and DFP samples, respectively. Two Russian DFP samples contained 1.51 and 1.54% Mg. Chlorine levels were generally quite low (.002 to .020%); however, two precipitated D-MCP samples contained .12 and 1.47% Cl. Iron levels were high (.24 to 1.41%) in all samples except the bone-precipitated D-MCP (.039%), and the reference standard, calcium phosphate, dibasic dihydrate, USP (.029%). Levels of Cu, Mn, and Zn were quite variable. Cadmium varied from < 1 ppm in the DFP samples to 67 ppm in one experimental M-DCP. Vanadium levels varied from 20 to 796 ppm in one experimental M-DCP sample. Fluorine levels were in the acceptable range, .05 to .21%.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Levels of various elements of concern in feed phosphates of domestic and foreign origin. 820 31

Exotoxin A production in Pseudomonas aeruginosa is a complicated and highly regulated process that involves several genes. In this report, we describe the isolation of a new toxA regulatory gene (ptxR) which affects exotoxin A production in P. aeruginosa. In an iron-deficient medium, the presence of a plasmid carrying ptxR in P. aeruginosa PAO1 resulted in a four-to fivefold increase in exotoxin A synthesis. No effect was observed on the levels of elastase, phospholipase C, exoenzyme S, and alkaline protease. Using subcloning and complementation experiments, ptxR was localized to a 2.1 kb Kpnl-Bg/II fragment. Nucleotide sequence analysis revealed the presence of an open reading frame which encodes a 34.97 kDa protein (PtxR). The size of the predicted PtxR compares closely with the 34 kDa PtxR that was synthesized in Escherichia coli using the T7 expression system. The deduced amino acid sequence of PtxR is homologous to that of several members of the LysR family of transcriptional activators. The amino-terminus region of PtxR contains a putative helix-turn-helix DNA-binding motif. Specific ptxR-deletion mutants in P. aeruginosa strains PAO1 and PA103 were constructed. In comparison with their parent strains, both mutants showed a significant reduction in the level of exotoxin A activity. However, upon extensive subculturing, the level of exotoxin A produced by the PAO1::ptxR mutant was similar to that of PAO1. Transcriptional studies, using both toxA-lacZ fusion and RNA analysis, confirmed that ptxR increases toxA and regA transcription. These results suggest that ptxR regulates (through regA) exotoxin A production at the transcriptional level.
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PMID:Isolation and characterization of a Pseudomonas aeruginosa gene, ptxR, which positively regulates exotoxin A production. 884 37


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