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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ferric uptake regulator (Fur) protein is known to act as a Fe2+-dependent transcriptional repressor of bacterial promoters. Here, we show that, in Helicobacter pylori, Fur can mediate the regulation of iron-activated genes in contrast to classical Fur regulation, in which iron acts as a co-repressor. Inactivation of the fur gene in the chromosome of H. pylori resulted in the derepression of a 19 kDa protein that was identified by N-terminal sequencing as the non-haem-containing ferritin (Pfr). Growth of the wild-type H. pylori strain on media treated with increasing concentrations of FeSO4 resulted in induction of transcription from the Ppfr promoter and, conversely, depletion of iron resulted in repression of Ppfr, indicating that this promoter is iron activated. In the fur mutant, the Ppfr promoter is constitutively highly expressed and no longer responds to iron, indicating that the Fur protein mediates this type of iron regulation. Footprinting analysis revealed that Fur binds to the Ppfr promoter region and that Fe2+ decreases the efficiency of binding. In contrast, Fe2+ increased the affinity of Fur for a classical Fur-regulated promoter, the iron-repressed frpB gene promoter. To our knowledge, this is the first evidence of direct interaction between the Fur protein and the promoter of an iron-activated (-derepressed) gene. Our results support a model in which the iron status of the Fur protein differentially alters its affinity for operators in either iron-repressed or iron-activated genes.
Mol Microbiol 2001 Dec
PMID:The Fur repressor controls transcription of iron-activated and -repressed genes in Helicobacter pylori. 1188 60

The recent development of endothelin-1 (ET-1) antagonists and their potential use in the treatment of human disease raises questions as to the role of ET-1 in the pathophysiology of such cardiovascular ailments as hypertension, heart failure, renal failure and atherosclerosis. It is still unclear, for example, whether activation of an endogenous ET-1 system is itself the primary cause of any of these ailments. In that context, the phenotypic manifestations of chronic ET-1 overproduction may provide clues about the tissues and systems affected by ET-1. We therefore established two lines of transgenic mice overexpressing the ET-1 gene under the direction of its own promoter. These mice exhibited low body weight, diminished fur density and two- to fourfold increases in the ET-1 levels measured in plasma, heart, kidney and aorta. There were no apparent histological abnormalities in the visceral organs of young (8 weeks old) transgenic mice, nor was their blood pressure elevated. In aged (12 months old) transgenic mice, however, renal manifestations, including prominent interstitial fibrosis, renal cysts, glomerulosclerosis and narrowing of arterioles, were detected. These pathological changes were accompanied by decreased creatinine clearance, elevated urinary protein excretion and salt-dependent hypertension. It thus appears that mild, chronic overproduction of ET-1 does not primarily cause hypertension but triggers damaging changes in the kidney which lead to the susceptibility to salt-induced hypertension.
J Mol Med (Berl) 2002 Feb
PMID:Renal damage and salt-dependent hypertension in aged transgenic mice overexpressing endothelin-1. 1190 42

The extracellular zona pellucida surrounding mammalian eggs is formed by interactions of the ZP1, ZP2, and ZP3 glycoproteins. Female mice lacking ZP2 or ZP3 do not form a stable zona matrix and are sterile. The three zona proteins are synthesized in growing oocytes and secreted prior to incorporation into the zona pellucida. A well-conserved furin site upstream of a transmembrane domain near the carboxyl terminus of each has been implicated in the release of the zona ectodomains from oocytes. However, mutation of the furin site (RNRR --> ANAA) does not affect the intracellular trafficking or secretion of an enhanced green fluorescent protein (EGFP)-ZP3 fusion protein in heterologous somatic cells. After transient expression in growing oocytes, normal EGFP-ZP3 and mutant EGFP-ZP3 associate with the inner aspect of the zona pellucida, which is distinct from the plasma membrane. These in vitro results are confirmed in transgenic mice expressing EGFP-ZP3 with or without the mutant furin site. In each case, EGFP-ZP3 is incorporated throughout the width of the zona pellucida and the transgenic mice are fertile. These results indicate that the zona matrix accrues from the inside out and, unexpectedly, suggest that cleavage at the furin site is not required for formation of the extracellular zona pellucida surrounding mouse eggs.
Mol Cell Biol 2002 May
PMID:Conserved furin cleavage site not essential for secretion and integration of ZP3 into the extracellular egg coat of transgenic mice. 1194 Jun 68

The estimation of milk consumption in free-ranging seals using tritium dilution techniques makes the key assumption that the animals drink no pre-formed water during the experimental period. However, frequent observations of unweaned Antarctic fur seal pups drinking water at Iles Kerguelen necessitated the testing of this assumption. We estimated water flux rates of 30 pups (10.7+/-0.3 kg) in four experimental groups by isotopic dilution over 4 days. The groups were: (1) pups held in an open air enclosure without access to water to estimate fasting metabolic water production (MWP); (2) free-ranging pups not administered additional water; (3) pups held in an open air enclosure and given a total of 300 ml of fresh water to verify technique accuracy; and (4) free-ranging pups given 200 ml of fresh water. Pups without access to water exhibited water flux rates (20.5+/-0.8 ml kg(-1)d(-1)), which were significantly lower than those observed for the free-ranging group (33.0+/-1.7 ml kg(-1) d(-1)). Mean estimated pre-formed water intake for the free-ranging experimental groups was 12.6 ml kg(-1) d(-1). Thus, MWP, measured as total water intake during fasting, may be significantly over-estimated in free-ranging Antarctic fur seal pups at Iles Kerguelen and at other sites and subsequently milk intake rates may be underestimated.
Comp Biochem Physiol A Mol Integr Physiol 2002 Jun
PMID:Drinking behaviour and water turnover rates of Antarctic fur seal pups: implications for the estimation of milk intake by isotopic dilution. 1202 Jun 48

The Staphylococcus aureus DtxR-like protein, MntR, controls expression of the mntABC and mntH genes, which encode putative manganese transporters. Mutation of mntABC produced a growth defect in metal-depleted medium and increased sensitivity to intracellularly generated superoxide radicals. These phenotypes resulted from diminished uptake of manganese and were rescued by the addition of excess Mn(II). Resistance to superoxide was incompletely rescued by Mn(II) for STE035 (mntA mntH), and the strain had reduced virulence in a murine abscess model of infection. Expression of mntABC was repressed by Mn(II) in an MntR-dependent manner, which contrasts with the expression of mntH that was not repressed in elevated Mn(II) and was decreased in an mntR mutant. This demonstrates that MntR acts as a negative and positive regulator of these loci respectively. PerR, the peroxide resistance regulon repressor, acts with MntR to control the expression of mntABC and manganese uptake. The expression of the PerR-regulated genes, katA (catalase), ftn (ferritin) and fur (ferric uptake regulator), was diminished in STE031 (mntR) when grown in excess Mn(II). Therefore, the control of Mn(II)-regulated members of the PerR regulon and the Fur protein is modulated by MntR through its control of Mn(II) uptake. The co-ordinated regulation of metal ion homeostasis and oxidative stress resistance via the regulators MntR, PerR and Fur of S. aureus is discussed.
Mol Microbiol 2002 Jun
PMID:MntR modulates expression of the PerR regulon and superoxide resistance in Staphylococcus aureus through control of manganese uptake. 1202 79

By using differential display PCR, we obtained a cDNA clone encoding a gloverin homologue from the cabbage looper, Trichoplusia ni. The expression of the gene was induced by bacterial infections. The gene codes for a 174 amino acid residue protein, including a signal sequence and a prosegment. The deduced mature protein is 14 kDa and shows 58% and 49% identity to P2 from Helicoverpa armigera and to Hyalophora gloveri gloverin, respectively. The protein was detected in hemolymph and hemocytes from bacteria-immunized animals. We expressed gloverin using the baculovirus expression system. N-terminal amino acid sequence analysis showed that the purified protein contained a propart. This progloverin inhibited the growth of E. coli and the activity is comparable to that of H. gloveri mature gloverin. Processing of progloverin was possible in vitro, using human furin.
Insect Biochem Mol Biol 2002 Jul
PMID:Trichoplusia ni gloverin, an inducible immune gene encoding an antibacterial insect protein. 1204 96

Sea otter (Enhydra lutris) populations experienced widespread reduction and extirpation due to the fur trade of the 18th and 19th centuries. We examined genetic variation within four microsatellite markers and the mitochondrial DNA (mtDNA) d-loop in one prefur trade population and compared it to five modern populations to determine potential losses in genetic variation. While mtDNA sequence variability was low within both modern and extinct populations, analysis of microsatellite allelic data revealed that the prefur trade population had significantly more variation than all the extant sea otter populations. Reduced genetic variation may lead to inbreeding depression and we believe sea otter populations should be closely monitored for potential associated negative effects.
Mol Ecol 2002 Oct
PMID:Loss of genetic diversity in sea otters (Enhydra lutris) associated with the fur trade of the 18th and 19th centuries. 1229 34

The Bacillus subtilis ferric uptake repressor (Fur) protein coordinates a global transcriptional response to iron starvation. We have used DNA microarrays to define the Fur regulon and the iron starvation stimulon. We identify 20 operons (containing 39 genes) that are derepressed both by mutation of fur and by treatment of cells with the iron chelator 2,2'-dipyridyl. These operons are direct targets of Fur regulation as judged by DNase I footprinting. Analyses of lacZ reporter fusions to six Fur-regulated promoter regions reveal that repression is highly selective for iron. In addition to the Fur regulon, iron starvation induces members of the PerR regulon and leads to reduced expression of cytochromes. However, we did not find any evidence for genes that are directly activated by Fur or repressed by Fur under iron-limiting conditions. Although genome searches using the 19 bp Fur box consensus are useful in identifying candidate Fur-regulated genes, some genes associated with Fur boxes are not demonstrably regulated by Fur, whereas other genes are regulated from sites with little apparent similarity to the conventional Fur consensus.
Mol Microbiol 2002 Sep
PMID:Global analysis of the Bacillus subtilis Fur regulon and the iron starvation stimulon. 1235 29

Furin catalyses a simple biochemical reaction--the proteolytic maturation of proprotein substrates in the secretory pathway. But the simplicity of this reaction belies furin's broad and important roles in homeostasis, as well as in diseases ranging from Alzheimer's disease and cancer to anthrax and Ebola fever. This review summarizes various features of furin--its structural and enzymatic properties, intracellular localization, trafficking, substrates, and roles in vivo.
Nat Rev Mol Cell Biol 2002 Oct
PMID:Furin at the cutting edge: from protein traffic to embryogenesis and disease. 1236 Jan 92

The ferric uptake regulator protein Fur regulates iron-dependent gene expression in bacteria. In Helicobacter pylori it has been shown to regulate iron-activated and iron-repressed genes. In this study, we show that H. pylori Fur protein regulates transcription from its own sigma 80 promoter P fur in response to iron. Footprinting analysis shows that Fur binds at three distinct operators at P fur overlapping and proximal to the promoter elements. Site-directed mutagenesis of the proposed iron-binding site of the protein results in derepression of P fur and the loss of iron regulation. In vivo oligomerization assays reveals that the C-terminus of Fur is necessary for multimerization of the protein and that the mutations do not affect this activity. Molecular and phenotypic analysis of the mutant proteins provides evidence that the iron-binding site controls the specific affinity of Fur for the operators at P fur and hence its repressive ability. In summary, the data presented are consistent with a model in which Fur acts as a rheostat of transcription to autoregulate its own expression in response to iron, which in turn controls expression of iron-induced and iron-repressed genes, providing maintenance of homeostasis.
Mol Microbiol 2002 Nov
PMID:Autoregulation of Helicobacter pylori Fur revealed by functional analysis of the iron-binding site. 1242 15


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