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)

Ubiquitin is an ubiquitous 76 aminoacids protein that is present in all cellular compartments. It intervenes in numerous functions of cell metabolism, and in particular in non-lysosomal (but also lysosomal) lysis of altered or short-lived proteins. Immunohistochemical studies have shown that it is present in many inclusions characteristic of neurodegenerative diseases, notably in Lewy bodies, neurofibrillary tangles of Alzheimer's disease, Pick bodies and also in inclusions characteristic of certain motor neuron diseases. The presence of ubiquitin in these inclusions raises 2 questions: (1) the nature of the target proteins, probably altered proteins of the cytoskeleton; (2) the significance of ubiquination: it might reflect the degeneration process or participate in the protection of cells against degeneration or be an active factor in programmed cell death.
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PMID:[Ubiquitin and degenerative diseases of the central nervous system]. 133 33

There are three species of ubiquitin gene transcripts in HeLa cells, termed UbA (approximately 0.7 kb), UbB (approximately 1.1 kb) and UbC (approximately 2.5 kb). In the present report, the UbC transcript was shown to accumulate up to 2.5-fold after irradiation with UV light or treatment with the phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA). The kinetic analysis indicated that the induced accumulation of UbC was rapid and transient; maximal accumulation of UbC was induced at 2.5 h after UV irradiation or 3 h after TPA treatment. Inhibition of a de novo protein synthesis by cycloheximide did not repress the induction of UbC after treatment with UV light and TPA. On the other hand, induction of UbA and UbB, in most cases, was not observed. UV-inducibility of human ubiquitin conjugating enzyme, E2(17k), was also tested. E2(17k) is a protein with high sequence similarity to the product of yeast DNA repair gene, RAD6. While the RAD6 gene has been reported to be inducible by UV light, no change in E2(17k) gene transcript was observed after UV irradiation.
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PMID:Induced accumulation of polyubiquitin gene transcripts in HeLa cells after UV-irradiation and TPA-treatment. 135 8

A pulse treatment of embryos of Norway spruce with cytokinin suppresses germinative development and induces the coordinate formation of adventitious buds from subepidermal cell layers. To analyse the patterns of gene expression associated with germination and the alterations induced by the bud induction treatment, we have isolated cDNA clones corresponding to genes that are differentially expressed in cytokinin-treated and untreated in vitro germinating embryos. One category of 14 clones hybridized to transcripts that were abundant specifically during germination. The expression of 8 of these genes was reduced by the bud induction treatment. Four clones, including one identified as a histone H2A gene, recognized transcripts that showed an increased abundance in bud-induced versus in vitro germinating embryos. A second category of 13 clones hybridized to transcripts that increased in abundance during post-germinative development of the seedling. Among these a subset of 8 clones, including an alpha-tubulin clone, corresponds to genes suppressed by the bud induction treatment, whereas 5 clones, including a gene with sequence similarity to polyubiquitin, were unaffected by the treatment. One clone hybridized to a message abundant in the seed, during early germination as well as in the vegetative bud, and showed 60% partial sequence identity to a barley (1----3)-beta-glucanase gene. Genes expressed exclusively in bud-induced or in vitro germinating embryos were not found. The results show that a major difference in gene expression between treated and untreated embryos is related to the shift from extensive cell proliferation to elongation and differentiation that occurs at the transition from germination to post-germinative development, and which is suppressed in the bud-induced embryos.
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PMID:Differential gene expression during germination and after the induction of adventitious bud formation in Norway spruce embryos. 137 81

Amyotrophic lateral sclerosis (ALS) patients with dementia were found to have ubiquitin-immunoreactive (IR) inclusions in the dentate granule cells of the hippocampus. These inclusions were also present in some patients with minor cognitive changes but otherwise typical ALS. Ubiquitin-IR inclusions were also found in neurons of superficial layers of the frontal and temporal cortex and in the entorhinal cortex in patients with ALS and dementia. These ubiquitin-IR inclusions were non-argyrophilic, and were not labelled by antibodies which identify Alzheimer's neurofibrillary tangles and Pick bodies, nor were they typical of cortical Lewy bodies. Our findings indicate that ubiquitin-IR inclusions in small neurons of the hippocampus, entorhinal area and neocortex are a characteristic feature of degeneration of non-motor cortex in ALS, and are particularly associated with cognitive impairment and dementia of frontal lobe type.
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PMID:Hippocampal and neocortical ubiquitin-immunoreactive inclusions in amyotrophic lateral sclerosis with dementia. 137 81

Ubiquitin belongs to a multigene family. In Drosophila two members of this family have been previously described. We report here the organization and expression of a third member, the DUb52 gene, isolated by screening a Drosophila melanogaster genomic library. This gene encodes an ubiquitin monomer fused to a 52-amino acid extension protein. There are no introns interrupting the coding sequence. Recently, it has been described that this extension encodes a ribosomal protein in Saccharomyces, Dictyostelium, and Arabidopsis. The present results show that the 5' regulatory region of DUb52 shares common features with the ribosomal protein genes of Drosophila, Xenopus and mouse, including GC- and pyrimidine-rich regions. Moreover, sequences similar to the consensus Ribo-box in Neurospora crassa have been identified. Furthermore, a sequence has been found that is similar to the binding site for the TFIIIA distal element factor from Xenopus laevis. The DUb52 gene is transcribed to a 0.9 kb mRNA that is expressed constitutively throughout development and is particularly abundant in ovaries. In addition, the DUb52 gene has been found to be preferentially transcribed in exponentially growing Drosophila cells.
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PMID:Structure and expression of the Drosophila ubiquitin-52-amino-acid fusion-protein gene. 138 84

This report deals with a comparative study on the expression of alpha B crystallin, ubiquitin, stress-response protein 27 (srp 27), srp 72 and phosphorylated neurofilament protein (pNFP) by ballooned neurons in Pick's disease, Creutzfeldt-Jakob disease (CJD), amyotrophic lateral sclerosis (ALS), leptomeningeal carcinomatosis, anterior spinal artery syndrome and pellagra. Immunohistochemical techniques were used. alpha B Crystallin was expressed by the majority of ballooned neurons of Pick's disease and CJD, but not by those of the other disorders. Ubiquitin and srp 27 expression was also restricted to abnormal neurons of Pick's disease and CJD, but the proportion of stained cells was less than that expressing alpha B-crystallin. There was no evidence of ballooned neurons expressing srp 72. Except for those of pellagra patients, phosphorylated neurofilament protein (pNFP) was detected in most abnormal neurons. Our results suggest that the mechanisms involved in formation and maintenance of swollen neurons in Pick's disease and CJD may be different than those of ballooned neurons in the other entities studied.
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PMID:Comparative immunohistochemical study on the expression of alpha B crystallin, ubiquitin and stress-response protein 27 in ballooned neurons in various disorders. 138 40

Ubiquitin in normal cells may be important in degrading or transferring short-lived or aberrant proteins to lysosomal dense bodies. To examine its role in degrading proteins produced by a chemical insult, changes in the distribution of ubiquitin and the carboxy-terminal hydrolase, PGP 9.5, have been studied in rat hippocampal neurons and cerebellar Purkinje cells in trimethyltin intoxication. Here tubulovesicular dense bodies (TVBs) form from 12h onwards associated with vacuolation of the Golgi apparatus. Striking accumulations of lysosomal dense bodies follow in hippocampal pyramidal cells but not in cerebellar Purkinje cells; many of the hippocampal neurons later die, while the Purkinje cells generally survive. Ubiquitin immunoreactivity was diffusely increased in hippocampal pyramidal and Purkinje cells 6 h after dosing. By 12 h both diffuse and granular ubiquitin immunoreactivity was present that intensified over 24 and 48 h. Both by light and electron microscopy TVBs showed ubiquitin immunoreactivity, but dense bodies in hippocampal perikarya did not stain with an anti-ubiquitin antibody. PGP 9.5 immunoreactivity was not altered in hippocampal cells at any time, while Purkinje and Golgi cell dendrites and perikarya showed intensified labelling at 3 h that reached a peak of 12 h. At 48 h Western blot analysis of hippocampal homogenates showed significant increases in high molecular weight (HMW) ubiquitin conjugates, while cerebellar homogenates showed an increase in ubiquitin-histone conjugates. Northern blot analyses showed no change in ubiquitin or PGP9.5 gene expression in hippocampus or cerebellum. These findings suggest that the material in the TVBs in hippocampal cells is not being degraded by the ubiquitin system but passes ubiquitinated into the lysosomal system, while material in Purkinje cell TVBs is degraded by the ubiquitin system, suggesting it may have a different composition in each type of neuron.
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PMID:Ubiquitin, PGP 9.5 and dense body formation in trimethyltin intoxication: differential neuronal responses to chemically induced cell damage. 138 41

In the yeast, Saccharomyces cerevisiae, the disaccharide trehalose is a stress-related metabolite that accumulates upon exposure of cells to heat shock or a variety of non-heat inducers of the stress response. Here, we describe the influence of mutations in individual heat-shock-protein genes on trehalose metabolism. A strain mutated in three proteins of the SSA subfamily of 70-kDa heat-shock proteins (hsp70) overproduced trehalose during heat shock at 37 degrees C or 40 degrees C and showed abnormally slow degradation of trehalose upon temperature decrease from 40 degrees C to 27 degrees C. The mutant cells were unimpaired in the induction of thermotolerance; however, the decay of thermotolerance during recovery at 27 degrees C was abnormally slow. Since both a high content of trehalose and induced thermotolerance are associated with the heat-stressed state of cells, the abnormally slow decline of trehalose levels and thermotolerance in the mutant cells indicated a defect in recovery from the heat-stressed state. A similar albeit minor defect, as judged from measurements of trehalose degradation during recovery, was detected in a delta hsp104 mutant, but not in a strain deleted in the polyubiquitin gene, UB14. In all our experiments, trehalose levels were closely correlated with thermotolerance, suggesting a thermoprotective function of trehalose. In contrast, heat-shock proteins, in particular hsp70, appear to be involved in recovery from the heat-stressed state rather than in the acquisition of thermotolerance. Cells partially depleted of hsp70 displayed an abnormally low activity of neutral trehalase when shifted to 27 degrees C after heat shock at 40 degrees C. Trehalase activity is known to be under positive control by cAMP-dependent protein kinases, suggesting that hsp70 directly or indirectly stimulate these protein-kinase activities. Alternatively, hsp70 may physically interact with neutral trehalase, thereby protecting the enzyme from thermal denaturation.
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PMID:The 70-kilodalton heat-shock proteins of the SSA subfamily negatively modulate heat-shock-induced accumulation of trehalose and promote recovery from heat stress in the yeast, Saccharomyces cerevisiae. 144 65

Programmed cell death (PCD) is a fundamental component of development in virtually all animals. Despite the ubiquity of this phenomenon, little is known about what tells a cell to die, and less still about the physiological and molecular mechanisms that bring about death. One system that has proven to be very amenable for the study of PCD is the intersegmental muscle (ISM) of the tobacco hawkmoth Manduca sexta. These giant muscle cells are used during the eclosion (emergence) behavior of the adult moth, and then die during the subsequent 30 h. This review uses the ISMs as a model system to address questions that are basic to any cell death system, including the following: (1) how do cells know when to die; (2) what physiological changes accompany death; (3) what are the molecular mechanisms that mediate death; and (4) do all cells die by the same process? For the ISMs, the trigger for PCD is a decline in the circulating titer of the insect molting hormone, 20-hydroxyecdysone (20-HE). During cell death there are rapid decreases in both the myofibrillar sensitivity to intracellular calcium and the resulting force of fiber contraction. The ability of the ISMs to undergo PCD requires the repression and activation of specific genes. Two of the repressed genes encode actin and myosin. One of the upregulated presumptive cell-death genes encodes polyubiquitin, which appears to play a critical role in the rapid proteolysis that accompanies ISM death.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Insect muscle as a model for programmed cell death. 146 90

Under conditions unfavorable to growth, the nematode Caenorhabditis elegans enters a developmentally arrested stage, the dauer larva. We have examined gene expression in the dauer larva and during recovery from the dauer stage. Run-on transcription assays with isolated nuclei reveal a depression of general RNA polymerase II transcription to 11-17% of that in other stages. Transcription of individual gene families (including actin, collagen, hsp70, and histone) is similarly depressed relative to actively growing stages. Dauer larvae are, however, capable of being induced for heat shock messages, indicating that they are competent to initiate and elongate transcripts. For most genes surveyed, reduced transcription in dauer larvae correlates with a decrease in message abundance. Hsp70 mRNA, however, is transcribed at lower rates but accumulates at levels comparable to those in other stages. Interestingly, dauer larvae are 15-fold enriched in a mRNA for a C. elegans hsp90 gene. Hsp90 mRNA accumulation is regulated at least in part by differential stability. Dauer larvae thus appear to have a unique pattern of gene expression. Upon placement in food, dauer larvae reenter the developmental pathway as late-stage larvae. Dauer recovery is accompanied by a temporally regulated sequence of gene expression. At least four distinct patterns of gene expression can be distinguished during exit from the dauer stage. Steady-state levels of hsp70 and polyubiquitin mRNA rise sharply within 75 min of recovery before declining by the fourth hour. Actin and histone mRNAs increase steadily following 2-4 hr of recovery, whereas myosin mRNA increases after 10 hr. In contrast, hsp90 mRNA declines sharply within the first 75 min of recovery. Changes in mRNA populations during dauer formation and exit may be physiologically relevant.
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PMID:Gene expression in the Caenorhabditis elegans dauer larva: developmental regulation of Hsp90 and other genes. 157 99


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