Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P62988 (Ubiquitin)
 4,326 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Activation of Saccharomyces cerevisiae trehalase by heat shock was shown in all strains tested, including mutants in which the response to a glucose signal was absent. A low concentration of cAMP favored the response as seen in 2nd log cells or in ras2 and cyr1ts mutant strains. The heat shock effect upon trehalase activity was not observed under conditions of catabolite repression. 2. Neither hexokinase PII nor the heat shock protein hsp26 seemed to be involved in the activation of trehalase by heat shock. However, mutant strains deleted in the polyubiquitin gene showed only a 2-fold activation of the enzyme while in control strains a 5- to 7-fold irreversible activation was observed. 3. An alternative mechanism of trehalase activation by removal of an inhibitor through ligation with ubiquitin is discussed. Activation by cAMP-independent phosphorylation is also considered.
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PMID:Activation of yeast trehalase by heat shock. 166 26

The heat shock/stress response is characterized by the induction of several highly evolutionarily conserved proteins during thermal stress, chemical stress, or glucose starvation. It has recently been recognized that members of the stress protein family are synthesized constitutively and subserve functions that are critical to protein folding during intracellular transport. In this study we examined the expression of heat shock/stress proteins in human mononuclear phagocytes, cells dependent on intracellular transport for Ag processing, Ag presentation, generation of reactive oxygen intermediates, and secretion of proinflammatory and antiinflammatory polypeptides. The results indicate that there are distinct patterns in expression of individual members of the highly homologous SP70, SP90, and ubiquitin gene families during different stress states. There is a marked increase in expression of the heat-inducible form of SP70 and SP90 in human monocytes during heat shock. Expression of GRP 78/BiP and GRP 94 increases predominantly during glucose starvation but also increases during heat shock. Ubiquitin gene expression increases during both heat shock and glucose starvation. There is no change in synthesis of the constitutive form of SP 70 or of the ubiquitin activating enzyme E1 during heat shock or glucose starvation. Synthesis of the constitutive form of SP 70 and novel SP 90-like polypeptides increase during endotoxin-mediated inflammatory activation. One intracellular transport process of the mononuclear phagocyte, secretion of specific proinflammatory and antiinflammatory polypeptides, is affected by glucose starvation and by heat shock.
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PMID:Expression of stress proteins in human mononuclear phagocytes. 188 Apr 18

UBI4, the polyubiquitin gene of Saccharomyces cerevisiae, is expressed at a low level in vegetative cells, yet induced strongly in response to starvation, cadmium, DNA-damaging agents and heat shock. UBI4 is also expressed at a higher basal level in cells growing by respiration as compared to glucose-repressed cells growing by fermentation. This higher UBI4 expression of respiratory cultures probably helps to counteract the greater oxidative stress of respiratory growth. The effects of inactivating UBI4 on high temperature viability are more marked with respiratory cultures. Also loss of UBI4 leads to a considerably increased rate of killing of respiring cells by hydrogen peroxide, whereas the same gene inactivation has relatively little effect on the peroxide sensitivity of cells in which mitochondrial functions are repressed. This is the first study to reveal that ubiquitin levels in cells can influence their ability to withstand oxidative stress.
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PMID:Polyubiquitin gene expression contributes to oxidative stress resistance in respiratory yeast (Saccharomyces cerevisiae). 819 89

Clathrin-mediated vesicular transport is important for normal growth of the yeast Saccharomyces cerevisiae. Previously, we identified a genetic locus (SCD1) that influences the ability of clathrin heavy-chain-deficient (Chc-) yeast cells to survive. With the scd1-v allele, Chc- yeast cells are viable but grow poorly; with the scd1-i allele, Chc- cells are inviable. To identify the SCD1 locus and other genes that can rescue chc1 delta scd1-i cells to viability, a multicopy suppressor selection strategy was developed. A strain of scd1-i genotype carrying the clathrin heavy-chain gene under GAL1 control (GAL1:CHC1) was transformed with a YEp24 yeast genomic library, and colonies that could grow on glucose were selected. Plasmids from six distinct genetic loci, none of which encoded CHC1, were recovered. One of the suppressor loci was shown to be UBI4, the polyubiquitin gene. UBI4 rescues only in high copy number and is not allelic to SCD1. The conjugation of ubiquitin to intracellular proteins can mediate their selective degradation. Since UBI4 is required for survival of yeast cells under stress and is induced during starvation, ubiquitin expression in GAL1:CHC1 cells was examined. After a shift to growth on glucose to repress synthesis of clathrin heavy chains, UBI4 mRNA levels were elevated > 10-fold, whereas the quantity of free ubiquitin declined severalfold relative to that of Chc+ cells. In addition, novel higher-molecular-weight ubiquitin conjugates appeared in clathrin-deficient cells. We suggest that higher levels of ubiquitin are required for turnover of mislocalized or improperly processed proteins that accumulate in the absence of clathrin and that ubiquitin may play a general role in turnover of proteins in the secretory or endocytic pathway.
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PMID:Suppressors of clathrin deficiency: overexpression of ubiquitin rescues lethal strains of clathrin-deficient Saccharomyces cerevisiae. 838 Feb 27

We examined ubiquitination and ubiquitin-mediated degradation of glycated protein by rabbit reticulocyte lysate fraction II (ubiquitin-free preparation). Non-glycated lysozyme and three glycated lysozyme preparations with different glucose binding ratios were used as substrates. Glycation sites of the lysozyme were mostly the epsilon-NH2 group of lysine residues, since modification at the alpha-NH2 group of the amino terminal was not detectable. Ubiquitin was conjugated with three glycated lysozyme preparations, which contained 1.4, 2.8 and 4.5 mol glucose per mol, by fraction II supplemented with hemin. The extent of formed conjugates was reduced 81, 72 and 56% of those of ubiquitin-non-glycated lysozyme conjugates, respectively. Additionally, ubiquitin-mediated degradation of the resultant conjugates was reduced and their respective rates were 97, 56 and 19% of that of the non-glycated lysozyme. These results indicated that both ubiquitin conjugation and ubiquitin-mediated degradation of the lysozyme were inhibited by nonenzymatic glucose binding to the lysozyme.
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PMID:Inhibitory effect of nonenzymatic glycation on ubiquitination and ubiquitin-mediated degradation of lysozyme. 838 87

Endothelial cells have been shown to play a major role in the pathophysiology of various diseases including ischemic heart disease and viral infection leading to myocarditis or dilated cardiomyopathy, conditions in which stress proteins (heat shock protein-hsp; glucose-related protein - grp) are likely to be involved. For further characterization of stress proteins and their possible role in these diseases, the major stress proteins in human endothelial cells were separated by two-dimensional polyacrylamide gel electrophoresis with immobilized pH gradients in the first dimension and identified by immunoblotting and either N-terminal or internal amino acid sequencing, respectively. Ubiquitin, hsp27, hsp60, hsp70, heat shock cognate protein 70, grp78 and grp75 were found to be constitutively expressed; hsp72 was found in stressed cells, exclusively, in line with results obtained in other human cell lines. Three additional proteins with molecular masses between 34 and 40 were regularly detected in stressed cells that were found to have identical amino acid sequences with those of members of the hsp70 family.
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PMID:Identification of stress proteins in endothelial cells. 873 48

Carbon and nitrogen regulation of UBI4, the stress-inducible polyubiquitin gene of Saccharomyces cerevisiae, was investigated using a UBI4 promoter-LacZ fusion gene (UBI4-LacZ). Expression of this gene in cells grown on different media indicated that the UBI4 promoter is more active during growth on respiratory than on fermentable carbon sources but is not subject to appreciable control by nitrogen catabolite repression. UBI4-LacZ expression was virtually identical in cells having constitutively high (ras2, sra1-13) or constitutively low (ras2) levels of cyclic AMP-dependent protein kinase activity, indicating that this kinase does not exert a major influence on UBI4 expression. Catabolite derepression control of the UBI4 promoter was confirmed by measurements of UBI4-LacZ expression in hap mutant and wild-type strains before and after transfer from glucose to lactate. Mutagenesis of the perfect consensus for HAP2/3/4 complex binding at position -542 resulted in considerable reduction of UBI4 promoter derepression with respiratory adaptation in HAP wild-type cells and abolished the reduced UBI4-LacZ derepression normally seen when aerobic cultures of the hap1 mutant are transferred from glucose to lactate. This HAP2/3/4 binding site is therefore a major element contributing to catabolite derepression of the UBI4 promoter, although data obtained with hapl mutant cells indicated that HAP1 also contributes to this derepression. The HAP2/3/4 and HAP1 systems are normally found to activate genes for mitochondrial (respiratory) functions. Their involvement in mediating higher activity of the UBI4 promoter during respiratory growth may reflect the contribution of UBI4 expression to tolerance of oxidative stress.
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PMID:UBI4, the polyubiquitin gene of Saccharomyces cerevisiae, is a heat shock gene that is also subject to catabolite derepression control. 903 3

In Saccharomyces cerevisiae, the addition of glucose to cells growing on galactose induces internalization of the galactose transporter Gal2p and its subsequent proteolysis in the vacuole. Here we report that the essential step in Gal2p down-regulation is its ubiquitination through the Ubc1p-Ubc4p-Ubc5p triad of ubiquitin-conjugating enzymes and Npi1/Rsp5p ubiquitin-protein ligase. Moreover, Gal2p appears to be stabilized in mutant cells defective in the ubiquitin-hydrolase Npi2p/Doa4p, and the mutant phenotype can be reversed by overexpression of ubiquitin. An analysis of the fate of Gal2p in cells overexpressing wild-type ubiquitin as well as its variants incompetent to form polyubiquitin chains showed that monoubiquitination of Gal2p is sufficient to signal internalization of the protein into the endocytic pathway.
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PMID:Glucose-induced monoubiquitination of the Saccharomyces cerevisiae galactose transporter is sufficient to signal its internalization. 1132 36

During fasting and many systemic diseases, muscle undergoes rapid loss of protein and functional capacity. To define the transcriptional changes triggering muscle atrophy and energy conservation in fasting, we used cDNA microarrays to compare mRNAs from muscles of control and food-deprived mice. Expression of >94% of genes did not change, but interesting patterns emerged among genes that were differentially expressed: 1) mRNAs encoding polyubiquitin, ubiquitin extension proteins, and many (but not all) proteasome subunits increased, which presumably contributes to accelerated protein breakdown; 2) a dramatic increase in mRNA for the ubiquitin ligase, atrogin-1, but not most E3s; 3) a significant suppression of mRNA for myosin binding protein H (but not other myofibrillar proteins) and IGF binding protein 5, which may favor cell protein loss; 4) decreases in mRNAs for several glycolytic enzymes and phosphorylase kinase subunits, and dramatic increases in mRNAs for pyruvate dehydrogenase kinase 4 and glutamine synthase, which should promote glucose sparing and gluconeogenesis. During fasting, metallothionein mRNA increased dramatically, mRNAs for extracellular matrix components fell, and mRNAs that may favor cap-independent mRNA translation rose. Significant changes occurred in mRNAs for many growth-related proteins and transcriptional regulators. These transcriptional changes indicate a complex adaptive program that should favor protein degradation and suppress glucose oxidation in muscle. Similar analysis of muscles atrophying for other causes is allowing us to identify a set of atrophy-specific changes in gene expression.
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PMID:Patterns of gene expression in atrophying skeletal muscles: response to food deprivation. 1240 12

Concern for the health risk associated with occupational exposure to jet fuel has emerged in the Department of Defense. Jet propulsion fuel-8 (JP-8) is the fuel used in most US and North Atlantic Treaty Organization (NATO) jet aircraft, and will be the predominant fuel both for military land vehicles and aircraft into the twenty-first century. JP-8 exhibits reduced volatility and lower benzene content as compared to JP-4, the predominant military aircraft fuel before 1992, possibly suggesting greater occupational exposure safety. However, the higher rates of occupational exposure through fueling and maintenance of increasingly larger numbers of aircraft/vehicles raise concerns with respect to toxicity. Clinical studies of workers experiencing long-term exposure to certain jet fuels demonstrated deficits in CNS function, including fatigue, neurobehavioral changes, psychiatric disorders, and abnormal electroencephalogram (EEG). In the present study, cDNA nylon arrays (Atlas Rat 1.2 Array, Clontech Laboratories, Palo Alto, CA) were utilized to measure changes in gene expression in whole brain tissue of rats exposed repeatedly to JP-8, under conditions that simulated possible real-world occupational exposure (6 h/day for 91 days) to JP-8 vapor at 1,000 mg/m3. Gene expression analysis of the exposure group compared to the control group revealed a modulation of several genes, including glutathione S-transferase Yb2 subunit (GST Yb2); cytochrome P450 IIIAl (CYP3A1); glucose-dependent insulinotropic peptide (GIP); alpha1-proteinase inhibitor (alpha1-AT); polyubiquitin; GABA transporter 3 (GAT-3); and plasma membrane Ca2+-transporting ATPase (brain isoform 2) (PMCA2). The implications of these vapor-induced changes in gene expression are discussed.
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PMID:Identification of target genes responsive to JP-8 exposure in the rat central nervous system. 1253 71


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