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

Many factors which induce the stress response (heat shock protein synthesis) in eukaryotes also cause the formation of aberrant proteins. Such aberrant proteins are usually rapidly and selectively degraded in cells. Temperature step-up accelerates the degradation of a subset of normally stable proteins. This effect is transient and is confined to a narrow range of heat shock temperatures above which proteolysis is inhibited. The time course and extent of proteolysis elicited by a mild heat shock is consistent with data on the thermal transitions of cellular proteins. Biochemical and genetic evidence strongly supports the view that the ubiquitin system is primarily responsible for heat- or stress-damaged protein degradation in eukaryotic cells. It still remains to be determined how stress-damaged proteins are recognized by the ubiquitin system and selected for degradation. Ubiquitin-protein ligases (E3's) which attach multi-ubiquitin chains to proteins are thought to be responsible for the selection of proteins for degradation. Several species of E3 have recently been characterized. However, none of the known E3's seems to fulfil the role of selecting aberrant proteins for breakdown. Heat shock proteins which are thought to repair unfolded or misfolded proteins probably have a complementary function to the ubiquitin system which destroys damage proteins. The relationship between the ubiquitin system and the regulation of heat shock protein synthesis, which is still not understood, is discussed.
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PMID:Effect of stress on protein degradation: role of the ubiquitin system. 166 97

Exposure of cells to physical (eg, heat) or chemical (eg, alcohol) stress results in increased synthesis of a set of highly conserved polypeptides termed heat shock proteins (HSPs), among which the 70-kd protein (HSP 70) is one of the most consistently inducible and highly conserved. This HSP has adenosine triphosphate-binding properties and is known to associate strongly with cytoskeletal structures that are usually disrupted on injury by heat or alcohol. Some HSPs apparently function as accessories to a nonlysosomal, adenosine triphosphate-dependent proteolytic system that binds and digests away stress-generated abnormal or denatured proteins after their conjugation with ubiquitin, a small HSP. Ubiquitin has been demonstrated immunocytochemically in Mallory bodies, which represent mainly degenerated intermediate filaments accumulated in hepatocytes of alcoholic-diseased liver. We immunostained histologic sections from patients with alcoholic liver disease using a polyclonal antibody raised against HSP 70. Strong diffuse cytoplasmic immunoreactivity was observed in many hepatocytes, including cells without Mallory bodies or fatty degeneration. Positive immunoreactivity for HSP 70 points to a possible involvement of this HSP in the pathogenesis of alcoholic liver disease. It also suggests that immunocytochemical detection of HSP 70 may serve as a more sensitive indicator of hepatocellular injury.
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PMID:Immunocytochemical detection of the 70-kd heat shock protein in alcoholic liver disease. 169 68

The effect of restrictive temperature on ubiquitin conjugation activity has been studied in cells of ts20, a temperature-sensitive cell cycle mutant of the Chinese hamster cell line E36. Ts20 is arrested in early G2 phase at nonpermissive temperature. Immunoblotting with antibodies to ubiquitin conjugates shows that conjugates disappear rapidly at restrictive temperatures in ts20 mutant but not in wild type E36 cells. The incorporation of 125I-ubiquitin into permeabilized ts20 cells is temperature-sensitive. Addition of extracts of another G2 phase mutant, FM3A ts85, with a temperature-sensitive ubiquitin activation enzyme (E1), to permeabilized ts20 cells at restrictive temperatures fails to complement their ubiquitin ligation activity. This indicates that the lesions in the two mutants are similar. Purified E1 from reticulocytes restores the conjugation activity of heat-inactivated permeabilized ts20 cells. Ubiquitin conjugation activity of cell-free extracts of ts20 cells was temperature-sensitive and could be restored by adding purified reticulocyte E1. Purified reticulocyte E2 or E3, on the other hand, did not restore the ubiquitin conjugation activity of heat-treated ts20 extracts. These results are consistent with the conclusion that ts20 has temperature-sensitive ubiquitin-activating enzyme (E1). The fact that two E1 mutants (ts20 and ts85) derived from different cell lines are arrested at the S/G2 boundary at restrictive temperatures strongly indicates that ubiquitin ligation is necessary for passage through this part of the cell cycle. The temperature thresholds of heat shock protein synthesis of ts20 and wild type E36 cells were identical. The implications of these findings with respect to a suggested role of ubiquitin in coupling between protein denaturation and the heat shock response are discussed.
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PMID:A Chinese hamster cell cycle mutant arrested at G2 phase has a temperature-sensitive ubiquitin-activating enzyme, E1. 304 11

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

Perturbations in keratin intermediate filament organization and Mallory body (MB) formation are associated with alcoholic hepatitis. Inducible heat shock proteins (HSPs) are expressed in a variety of liver diseases including alcoholic liver disease. Therefore, we investigated whether heat shock protein induction can lead to MB formation. Mice were primed by a 5-month feeding of griseofulvin (GF) or diethyl 1,4-dehydro-2,4,6-trimethyl-3,5-pyridinedicarboxylate (DDC) followed by drug withdrawal for 1 month. The animals were then subjected to an in vivo heat shock treatment or sham heat treatment. Liver morphology, HSP expression, liver regeneration (PCNA-labeled nuclei), and MB formation were monitored during a 7-day posttreatment period. Numerous MBs developed in the livers of mice exposed to GF or DDC for 5 months, but very few small MBs remained after 1-month withdrawal of either drug. No MBs were found at Day 1 post heat shock, whereas numerous MBs were observed at Day 7. The frequency of PCNA-labeled nuclei increased during the same period. At Day 1 posttreatment, a variable liver centrilobular necrosis was observed accompanied by a prominent increase in HSP-25 and HSP70 expression, but HSP-90 expression was not increased. In drug-primed mouse liver, a heat shock treatment induces the expression of specific HSPs prior to the formation of MBs, indicating that HSP expression may play a role in the pathogenesis of MB formation. We speculate that this role is through the protein unfolding function of HSP, which leads to the aggregation of the cytokeratins to form MBs as well as to polyubiquitin binding to these proteins in a manner analogous to amyloid formation.
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PMID:Heat shock in vivo induces Mallory body formation in drug primed mouse liver. 875 55

The intersegmental muscles (ISMs) of the tobacco hawkmoth, Manduca sexta, undergo programmed cell death (PCD) following adult eclosion in response to a decline in the circulating titer of the hormone 20-hydroxyecdysone. The ability of the ISMs to die requires de novo gene expression and a number of cDNAs representing differentially expressed genes have been isolated from condemned cells. One of the genes that is dramatically up-regulated with ISM death is polyubiquitin, which has been shown in many organisms to function as a heat shock protein and as an essential mediator of proteolysis. Northern blot analysis of ISM RNA samples pooled from multiple individuals demonstrated the presence of several polyubiquitin transcripts. In this study, we sought to determine: 1) if these transcripts were the product of multiple genes or multiple alleles, and 2) if all polyubiquitin genes/alleles in the moth are regulated by both heat shock and the endocrine signals that regulate death. Data from Southern blot analysis suggested that the Manduca genome has a single polyubiquitin gene that is represented by multiple alleles. Transcript analysis supported the hypothesis that all polyubiquitin alleles are regulated by both heat shock and the hormonal cues that regulate muscle death. Polyubiquitin transcripts accumulated to much higher levels and had longer half-lives following hormonal induction relative to that seen in response to heat shock. These data suggest that there are multiple polyubiquitin alleles in the laboratory population of Manduca, all of which share common regulatory sequences that drive expression to meet the needs for proteolysis involved in both heat stress and death.
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PMID:Allelic variation of the polyubiquitin gene in the tobacco hawkmoth, Manduca sexta, and its regulation by heat shock and programmed cell death. 903 86

The prognostic value of ubiquitin levels in cerebrospinal fluid (CSF) was studied in human global brain ischemia (anoxic-ischemic encephalopathy). Twenty four samples were collected from 13 patients who were resuscitated from cardio-pulmonary arrest and survived for at least 1 day. The outcome was classified according to the Glasgow Outcome Scale (GOS1-5). The ubiquitin levels (normal: 14.3 +/- 1.1 ng/ml, mean +/- S.E.M.) in neurologically symptomatic patients (GOS1-4) were 151 +/- 32.5 ng/ml on day 1-2 and elevated to 1,960 +/- 849 ng/ml on day 3-4. The Spearman's rank correlation of ubiquitin levels on day 3-4 and the GOS was -0.855, showing a better correlation than CSF neuron-specific enolase levels (r = -0.846). Ubiquitin is a heat shock protein associated with the degradation of abnormal cellular proteins. Thus, the elevation of CSF ubiquitin levels represents both its overproduction by a cytoprotective response to brain ischemia and its leakage from the damaged tissue. The present study suggests that the measurement of CSF ubiquitin level is useful for the early prognostic assessment of global brain ischemia.
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PMID:[An increase in cerebrospinal fluid ubiquitin in human global brain ischemia--a prognostic marker for anoxic-ischemic encephalopathy]. 950 64

To evaluate the significance of immunohistochemical staining of ubiquitin (heat shock protein) in the midbrain for the medico-legal diagnosis of fatal asphyxiation and drowning, we investigated forensic autopsy cases of fatal mechanical asphyxia (n = 18), manual/ligature strangulation (n = 9), hanging (n = 4), aspiration/choking (n = 5) and drowning (n = 16). These were compared to control groups (n = 30) consisting of fatalities from brainstem injury (n = 12) and acute myocardial infarction (n = 18). Ubiquitin was clearly demonstrated in the nuclei of pigmented substantia nigra neurons, showing two intranuclear staining patterns: a type of inclusion (possibly Marinesco bodies) and a diffuse staining. The diffuse staining was significantly more frequently observed in cases of drowning. The percentage of total ubiquitin positive neurons was frequently higher in strangulation (5.1-28.4%, mean 17.0%), aspiration/choking (5.3-32.0%, mean 17.6%) and drowning (7.0-34.1%, mean 19.8%), but relatively low in hanging (5.1-12.7%, mean 8.6%), brainstem injury (0-10.4%, mean 5.0%) and acute myocardial infarction (1.5-16.9%, mean 8.3%). These observations suggest that intranuclear ubiquitin immunoreactivity of the pigmented substantia nigra neurons in the midbrain was induced by a fatal severe stress on the central nervous system in asphyxiation and drowning.
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PMID:Intranuclear ubiquitin immunoreactivity of the pigmented neurons of the substantia nigra in fatal acute mechanical asphyxiation and drowning. 1159 72

Using homologous molecular probes, we examined the influence of equivalent temperature shifts on the in vivo expression of genes coding for a constitutive heat shock protein (Hsc70), heat shock proteins (Hsps) (Hsp70 and Hsp90), and polyubiquitin, after acclimation in the American lobster, Homarus americanus. We acclimated sibling, intermolt, juvenile male lobsters to thermal regimes experienced during overwintering conditions (0.4 +/- 0.3 degrees C), and to ambient Pacific Ocean temperatures (13.6 +/- 1.2 degrees C), for 4-5 weeks. Both groups were subjected to an acute thermal stress of 13.0 degrees C, a temperature shift previously found to elicit a robust heat shock response in ambient-acclimated lobsters. Animals were examined after several durations of acute heat shock (0.25-2 hours) and after several recovery periods (2-48 hours) at the previous acclimation temperature, following a 2-hour heat shock. Significant inductions in Hsp70, Hsp90, and polyubiquitin messenger RNA (mRNA) levels were found for the ambient-acclimated group. Alternatively, for the cold-acclimated group, an acute thermal stress over an equivalent interval resulted in no induction in mRNA levels for any of the genes examined. For the ambient-acclimated group, measurements of polyubiquitin mRNA levels showed that hepatopancreas, a digestive tissue, incurred greater irreversible protein damage relative to the abdominal muscle, a tissue possessing superior stability over the thermal intervals tested.
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PMID:Thermal acclimation and stress in the American lobster, Homarus americanus: equivalent temperature shifts elicit unique gene expression patterns for molecular chaperones and polyubiquitin. 1189 92


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