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

Ubiquitin is involved in the degradation of denatured proteins in the recovery process after various stresses. To clarify the different responses of the ubiquitin system in the hippocampal neurons after ischemia, we chose 7.5 min of sublethal forebrain ischemia in the rat. After 7.5 min of ischemia, ubiquitin-like immunoreactivity (UIR) in most of the hippocampal pyramidal cells, except for the interneurons, diminished after 3 h of reperfusion, but enhanced UIR and subsequent recovery of UIR were observed in the different hippocampal regions after 24 h of reperfusion. The most prolonged recovery of UIR in the hippocampal cells was observed in the CA1 neurons after 72 h of reperfusion. Immunoblot analysis of the proteins extracted from CA1 region showed that high-mol-wt ubiquitin conjugates (HMWUC) above 40 kDa increased, whereas free ubiquitin and ubiquitinated histone 2A decreased slightly after 4 h and 24 h of reperfusion. At 72 h of reperfusion, HMWUC decreased to the original level and free ubiquitin slightly increased beyond the control level. These results suggested that (1) diminished UIR does not always mean depletion of entire ubiquitin-protein conjugates; (2) even after sublethal ischemia, damaged proteins in the CA1 neurons may increase, and it may take a long time for elimination of these proteins.
 ...
PMID:Changes in ubiquitin and ubiquitin-protein conjugates in the CA1 neurons after transient sublethal ischemia. 166 59

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.
 ...
PMID:Activation of yeast trehalase by heat shock. 166 26

The presence of ubiquitin in ciliates was first demonstrated in Tetrahymena pyriformis. One clone--pTU2--presents two incomplete open reading frames and the putative polyubiquitin genes have been shown to be highly similar to those of other organisms. To further analyze the organization of this multigene family, several fragments of macronuclear DNA were cloned. We report here the isolation and characterization of one genomic clone (pTU20) that encodes a polyubiquitin gene (TU20) with five tandem repeats and presenting only one extra triplet CAA (Gln) upstream from the TGA. The promoter region of TU20 also presents a consensus heat shock element. The specific detection of RNA species with a synthetic oligonucleotide probe reveals that it corresponds to the 1.8 kb mRNA species whose expression is increased by temperature stress.
 ...
PMID:The macronuclear polyubiquitin gene of the ciliate Tetrahymena pyriformis. 166 85

Ubiquitin immunocytochemistry with an antiserum which reacts with ubiquitin-protein conjugates demonstrates the presence of ubiquitinated proteins in filamentous inclusions found in neurones in the major human neurodegenerative diseases, i.e. Alzheimer's disease, diffuse Lewy body disease, motor neurone disease. Ubiquitin immunohistochemistry has revolutionized the neuropathological diagnosis of dementia showing that diffuse Lewy body disease is not, as previously supposed, a rare cause of dementia. The filamentous inclusions in neurones in the human neurodegenerative diseases can be divided into at least two types based on recent immunocytochemical studies. We have shown that a ubiquitin-carboxyl terminal hydrolase is present in Lewy bodies but not in neurofibrillary tangles in Alzheimer's disease. This observation is significant since it indicates that molecular pathological mechanisms in neurones in diffuse Lewy body disease are fundamentally different to Alzheimer's disease. Ubiquitin-protein conjugates are also found in vacuoles in areas of granulovacuolar degeneration in hippocampal neurones in Alzheimer's disease and in granulovacuoles in neurones of scrapie infected mouse brain. These locations suggest that ubiquitinated protein are present in the lysosome-related system of neurones. We have recently shown that ubiquitin-protein conjugates are indeed enriched some 12-fold in the lysosomes of normal fibroblasts and lymphocytes.
 ...
PMID:The role of protein ubiquitination in neurodegenerative disease. 166 96

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.
 ...
PMID:Effect of stress on protein degradation: role of the ubiquitin system. 166 97

Covalent ligation of multiple copies of ubiquitin to proteins is known to target intracellular proteins for degradation by large molecular weight cytosolic proteinase(s). Ubiquitin protein conjugates are found in cytosolic cell compartments suggesting that ubiquitination may have multiple roles. We have detected ubiquitinated proteins in the lysosomal apparatus of normal fibroblasts and fibroblasts treated with lysosomal proteinase inhibitors. In contrast rabbit reticulocytes lack lysosomes. We present here direct evidence for ubiquitination of mitochondrial proteins during rabbit reticulocyte maturation. In addition ubiquitination appears to be associated with the terminal differentiation of human keratinocytes. These results suggest that: 1. ubiquitin-protein conjugates may be degraded lysosomally 2. organellar proteins may be degraded by the ubiquitin system 3. ubiquitination is involved in the programmed elimination of proteins and organelles from several cell types during differentiation.
 ...
PMID:The degradative fate of ubiquitin-protein conjugates in nucleated and enucleated cells. 166 98

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.
 ...
PMID:Immunocytochemical detection of the 70-kd heat shock protein in alcoholic liver disease. 169 68

Ultrastructural immunoreactivities of alpha B-crystallin, glial fibrillary acidic protein (GFAP), ubiquitin, and vimentin in Rosenthal fibers (RFs) isolated from an Alexander's disease brain were investigated using nonosmium and low-temperature embedding technique. The morphology of RFs embedded in Lowicryl K4M resin was well preserved after treatment with 0.5% Triton X-100. alpha B-crystallin immunoreactivity was present in RFs of various sizes and was the strongest in loosely scattered deposits, which were considered to be the initial stage of RFs. Glial fibrillary acidic protein immunoreactivity in RFs was heavy, homogeneous throughout RFs, and equivalent to that in networks of glial filaments. Immunoreactivities of both alpha B-crystallin and GFAP were mainly restricted to the high electron-dense areas within RFs and were proved to exist close to each other by double immunolabeling. Rosenthal fibers were negative for vimentin. Ubiquitin immunoreactivity was relatively homogeneous in RFs with small diameters, but in RFs with large diameters, the immunoreactivity diminished in the center. Based on these observations, combined with the tendency of self-aggregation of alpha B-crystallin, it is conceivable that RFs are huge aggregation products of alpha B-crystallin involving GFAP, and that ubiquitination may be a consequent phenomenon, as it may be in other intracytoplasmic inclusions, such as neurofibrillary tangles and Lewy bodies.
 ...
PMID:Rosenthal fibers share epitopes with alpha B-crystallin, glial fibrillary acidic protein, and ubiquitin, but not with vimentin. Immunoelectron microscopy with colloidal gold. 170 36

In the present work, a method based on an epitope-tagged ubiquitin derivative is described that allows for the unambiguous detection of ubiquitin-protein conjugates formed in vivo or in vitro. Expression in the yeast Saccharomyces cerevisiae of ubiquitin that has been tagged at its amino terminus with a peptide epitope results in the formation of tagged ubiquitin-protein conjugates that are detectable by immunoblotting with a monoclonal antibody that recognizes the tag. The expression of tagged ubiquitin has no adverse effect on vegetative growth and, moreover, can suppress the stress-hypersensitive phenotype of yeast lacking the polyubiquitin gene UBI4. We also show that tagged ubiquitin is correctly conjugated in vivo and in vitro to a short-lived test protein and can be covalently extended into the multimeric ubiquitin chain that is normally required for the degradation of this protein. Surprisingly, however, conjugation of tagged ubiquitin inhibits proteolysis. These and related results suggest that the amino-terminal region of ubiquitin is important in protease-substrate recognition and that the multiubiquitin chain is a dynamic transient structure. The potential of tagged ubiquitin for the identification and isolation of ubiquitin-protein conjugates and ubiquitin-related enzymes, and as a tool in mechanistic studies is discussed.
 ...
PMID:Epitope-tagged ubiquitin. A new probe for analyzing ubiquitin function. 171 71

Levels of ubiquitin, microtubule associated protein tau and tubulin were determined by immunoassays in homogenates of cerebrum and cerebellum of Alzheimer disease and aged control cases. Ubiquitin levels increased many fold in the cerebral cortex of Alzheimer disease cases and the increase correlated strongly with the degree of neurofibrillary changes in the tissue. The increase in ubiquitin was much less remarkable in the cerebral white matter. Cerebellum which is unaffected with neurofibrillary changes in Alzheimer disease had normal levels of ubiquitin both in gray matter and in white matter. There was an appreciable increase in abnormally phosphorylated tau in an Alzheimer disease brain with severe neurofibrillary degeneration, whereas the normal tau levels were increased only slightly. Tubulin was slightly decreased in the cerebral gray matter but not in the adjacent white matter. Marked increase in brain ubiquitin in Alzheimer disease suggests the role of ubiquitin in the pathobiology of Alzheimer disease.
 ...
PMID:Brain ubiquitin is markedly elevated in Alzheimer disease. 181 31


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>