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Query: UNIPROT:P62988 (Ubiquitin)
 4,326 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Conjugation of ubiquitin to intracellular proteins mediates their selective degradation in eukaryotes. In the yeast Saccharomyces cerevisiae, four distinct ubiquitin-coding loci have been described. UBI1, UBI2, and UBI3 each encode hybrid proteins in which ubiquitin is fused to unrelated sequences. The fourth gene, UBI4, contains five ubiquitin-coding elements in a head-to-tail arrangement, and thus encodes a polyubiquitin precursor protein. A precise, oligonucleotide-directed deletion of UBI4 was constructed in vitro and substituted in the yeast genome in place of the wild-type allele. ubi4 deletion mutants are viable as vegetative cells, grow at wild-type rates, and contain wild-type levels of free ubiquitin under exponential growth conditions. However, although ubi4/UBI4 diploids can form four initially viable spores, the two ubi4 spores within the ascus lose viability extremely rapidly, apparently a novel phenotype in yeast. Furthermore, ubi4/ubi4 diploids are sporulation-defective. ubi4 mutants are also hypersensitive to high temperatures, starvation, and amino acid analogs. These three conditions, while diverse in nature, are all known to induce stress proteins. Expression of the UBI4 gene is similarly induced by either heat stress or starvation. These results indicate that UBI4 is specifically required for the resistance of cells to stress, and that ubiquitin is an essential component of the stress response system.
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PMID:The yeast polyubiquitin gene is essential for resistance to high temperatures, starvation, and other stresses. 303 May 56

Ubiquitin is a 76-residue protein highly conserved among eukaryotes. Conjugation of ubiquitin to intracellular proteins mediates their selective degradation in vivo. We describe a family of four ubiquitin-coding loci in the yeast Saccharomyces cerevisiae. UB11, UB12 and UB13 encode hybrid proteins in which ubiquitin is fused to unrelated ('tail') amino acid sequences. The ubiquitin coding elements of UB11 and UB12 are interrupted at identical positions by non-homologous introns. UB11 and UB12 encode identical 52-residue tails, whereas UB13 encodes a different 76-residue tail. The tail amino acid sequences are highly conserved between yeast and mammals. Each tail contains a putative metal-binding, nucleic acid-binding domain of the form Cys-X2-4-Cys-X2-15-Cys-X2-4-Cys, suggesting that these proteins may function by binding to DNA. The fourth gene, UB14, encodes a polyubiquitin precursor protein containing five ubiquitin repeats in a head-to-tail, spacerless arrangement. All four ubiquitin genes are expressed in exponentially growing cells, while in stationary-phase cells the expression of UB11 and UB12 is repressed. The UB14 gene, which is strongly inducible by starvation, high temperatures and other stresses, contains in its upstream region strong homologies to the consensus 'heat shock box' nucleotide sequence. Elsewhere we show that the essential function of the UB14 gene is to provide ubiquitin to cells under stress.
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PMID:The yeast ubiquitin genes: a family of natural gene fusions. 303 23

Most of the increased protein degradation in muscle atrophy caused by starvation and denervation is due to activation of a non-lysosomal ATP-dependent proteolytic process. To determine whether expression of the ubiquitin-proteasome-dependent pathway is activated in atrophying muscles, we measured the levels of mRNA for ubiquitin (Ub) and proteasome subunits, and Ub content. After rats had been deprived of food for 1 or 2 days, the concentration of the two polyubiquitin (polyUb) transcripts increased 2-4-fold in the pale extensor digitorum longus muscle and 1-2.5-fold in the red soleus, whereas total muscle RNA and total mRNA content fell by 50%. After denervation of the soleus, there was a progressive 2-3-fold increase in polyUb mRNA for 1-3 days, whereas total RNA content fell. On starvation or denervation, Ub concentration in the muscles also rose by 60-90%. During starvation, polyUb mRNA levels also increased in heart, but not in liver, kidney, spleen, fat, brain or testes. Although the polyUb gene is a heat-shock gene that is induced in muscles under certain stressful conditions, the muscles of starving rats or after denervation did not express other heat-shock genes. On starvation or denervation, mRNA for several proteasome subunits (C-1, C-3, C-5, C-8 and C-9) also increased 2-4-fold in the atrophying muscles. When the food-deprived animals were re-fed, levels of Ub and proteasome mRNA in their muscles returned to control values within 1 day. In contrast, no change occurred in the levels of muscle mRNAs encoding cathepsin L, cathepsin D and calpain 1 on denervation or food deprivation. Thus polyUb and proteasome mRNAs increased in atrophying muscles in co-ordination with activation of the ATP-dependent proteolytic process.
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PMID:Increase in levels of polyubiquitin and proteasome mRNA in skeletal muscle during starvation and denervation atrophy. 774 90

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

Differential cDNA screening was used to identify genes expressed during the colonisation of rice leaves by the pathogenic fungus Magnaporthe grisea. This led to the identification of a gene, called UEP1, which encodes a ubiquitin extension protein. UEP1 was highly expressed 48 h after initial fungal infection of rice leaves when M. grisea is proliferating in the leaf epidermis but not yet causing disease symptoms. UEP1 appeared to be down-regulated after this time despite further extensive growth of the fungus throughout the leaf tissue. To investigate the potential role of ubiquitin in fungal pathogenesis we subsequently isolated UEP3 and PUB4, encoding a second ubiquitin extension protein and a polyubiquitin respectively. UEP1 was expressed abundantly during active growth of M. grisea in axenic culture but was down-regulated by starvation-stress. UEP3 showed a similar pattern of expression to UEP1 during the growth of M. grisea in culture and after environmental stress, but was not highly expressed during plant colonisation. PUB4 was highly expressed after environmental stress, but was not highly expressed during plant colonisation. UEP1 was found to be present in a much-higher copy number per haploid genome compared to UEP3 and PUB4. The restricted high-level expression of UEP1 suggests that M. grisea undergoes rapid ribosomal biogenesis and protein turnover during initial plant-tissue colonisation, which is regulated by a specific UEP1-encoded component of the M. grisea ubiquitin gene family.
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PMID:Identification of three ubiquitin genes of the rice blast fungus Magnaporthe grisea, one of which is highly expressed during initial stages of plant colonisation. 961 86

Although cell differentiation usually involves synthesis of new proteins, little is known about the role of protein degradation. In eukaryotes, conjugation to ubiquitin polymers often targets a protein for destruction. This process is regulated by deubiquitinating enzymes, which can disassemble ubiquitin polymers or ubiquitin-substrate conjugates. We find that a deubiquitinating enzyme, UbpA, is required for Dictyostelium development. ubpA cells have normal protein profiles on gels, grow normally, and show normal responses to starvation such as differentiation and secretion of conditioned medium factor. However, ubpA cells have defective aggregation, chemotaxis, cAMP relay, and cell adhesion. These defects result from low expression of cAMP pulse-induced genes such as those encoding the cAR1 cAMP receptor, phosphodiesterase, and the gp80 adhesion protein. Treatment of ubpA cells with pulses of exogenous cAMP allows them to aggregate and express these genes like wild-type cells, but they still fail to develop fruiting bodies. Unlike wild type, ubpA cells accumulate ubiquitin-containing species that comigrate with ubiquitin polymers, suggesting a defect in polyubiquitin metabolism. UbpA has sequence similarity with yeast Ubp14, which disassembles free ubiquitin chains. Yeast ubp14 cells have a defect in proteolysis, due to excess ubiquitin chains competing for substrate binding to proteasomes. Cross-species complementation and enzyme specificity assays indicate that UbpA and Ubp14 are functional homologs. We suggest that specific developmental transitions in Dictyostelium require the degradation of specific proteins and that this process in turn requires the disassembly of polyubiquitin chains by UbpA.
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PMID:A deubiquitinating enzyme that disassembles free polyubiquitin chains is required for development but not growth in Dictyostelium. 978 28

The ubiquitin encoding genes of Kluyveromyces lactis were cloned. Three genes, KlUBI1, KlUBI3 and KlUBI4, were found in this yeast, while in Saccharomyces cerevisiae there are four genes, UBI1, -2, -3 and -4. The UBI1/UBI2 duplication is thus absent from the K. lactis genome. General structural features of ubiquitin genes were very similar in these two species (presence of an intron in KlUBI1, fusion to ribosomal protein genes in KlUBI1 and KlUBI3, spacer-less polyubiquitin repeats in KlUBI4). Disruption or deletion of K. lactis ubiquitin genes showed that: (a) disruption of KlUBI1 was lethal (in S. cerevisiae, ubi1/ubi2 double deletion is lethal); (b) KlUBI3 is also an essential gene for cell growth; (c) deletion of KlUBI4 led to an increased sensitivity to high temperature, similar to the ubi4 mutation in S. cerevisiae, but, in contrast to the latter, the klubi4 mutant was not sensitive to carbon or nitrogen source starvation. The syntenic relationship of ubiquitin loci between K. lactis and S. cerevisiae genomes is also described.
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PMID:The ubiquitin-encoding genes of Kluyveromyces lactis. 1066 72

Using a polyubiquitin cDNA as a probe, we have isolated a clone (pPR3, a pEMBLYe23 derivative plasmid) containing the Candida albicans UBI3 gene coding for a fusion protein. This protein is formed by one ubiquitin subunit fused, at its C-terminus, to an unrelated peptide which is similar to the ribosomal protein encoded by the 3' tail of the Saccharomyces cerevisiae UBI3 gene. Southern blot analysis of chromosomal DNA probed with the 3' non-ubiquitin tail of UBI3 indicated that only one homologous gene is present in the C. albicans genome. Heterelogous expression of pPR3 in a S. cerevisiae ubi3 mutant strain complements the mutant phenotype (slow growth) conferred by the ubi3 defect; this provides direct evidence indicating that the clone contains the C. albicans UBI3 gene Northern blot analysis showed that UBI3 gene is expressed in yeast and germ-tube cells of C. albicans, although the UBI3 mRNA levels in starved yeast cells are below the detection limit; UBI3 mRNA drops to undetectable levels on shifting the temperature of growing yeast cells from 28 degrees C to 42 degrees C. When Northern blot analysis was performed using a specific probe for the polyubiquitin (UBI4) gene, no drop in the mRNA levels was detected following thermal upshift or in starved cells. These results indicate that stress conditions (starvation or thermal upshift) negatively regulate UBI3 expression (transcriptional arrest and/or enhanced mRNA decay), and suggest that UBI4 gene provides ubiquitin during the stress response. In addition, we failed to obtain C. albicans UBI3 null mutant cells by sequential disruption of both alleles using the hisG::URA3::hisG ('ura-blaster') cassette, suggesting that null mutants cells may be unable to grow on selective media after transformation.
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PMID:Molecular cloning and characterization of the Candida albicans UBI3 gene coding for a ubiquitin-hybrid protein. 1105 22


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