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 involved in cell-cycle control and DNA replication through a specific proteolytic pathway. Our previous studies demonstrated selected higher expression of a gene encoding ubiquitin-ribosomal protein S27a in poorly differentiated colon carcinoma cell lines. In this study, we evaluated this ubiquitin hybrid protein gene expression in surgical specimens of colon cancers. Northern blot analysis showed that ubiquitin hybrid protein messenger RNA was overexpressed in primary colon cancers compared with adjacent normal colon mucosae in 17 of 20 patients. Dot blot analysis of RNA of 27 tumor samples revealed significantly greater expression in higher Dukes' stage primary colon tumors and liver metastases. These data imply that protein translation machinery is highly activated during progression and metastasis of colon tumors, and that ubiquitin hybrid protein may be useful as a marker of biological aggressiveness.
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PMID:Ubiquitin hybrid protein gene expression during human colon cancer progression. 200 61

In eukaryotes, both natural and engineered fusions of ubiquitin to itself or other proteins are cleaved by processing proteases after the last (Gly76) residue of ubiquitin. Using the method of sib selection, and taking advantage of the fact that bacteria such as Escherichia coli lack ubiquitin-specific enzymes, we have cloned a gene, named UBP1, of the yeast Saccharomyces cerevisiae that encodes a ubiquitin-specific processing protease. With the exception of polyubiquitin, the UBP1 protease cleaves at the carboxyl terminus of the ubiquitin moiety in natural and engineered fusions irrespective of their size or the presence of an amino-terminal ubiquitin extension. These properties of UBP1 distinguish it from the previously cloned yeast protease YUH1, which deubiquitinates relatively short ubiquitin fusions but is virtually inactive with longer fusions such as ubiquitin-beta-galactosidase. The amino acid sequence of the 809-residue UBP1 lacks significant similarities to other known proteins, including the 236-residue YUH1 protease. Null ubp1 mutants are viable, and retain the ability to deubiquitinate ubiquitin-beta-galactosidase, indicating that the family of ubiquitin-specific proteases in yeast is not limited to UBP1 and YUH1.
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PMID:Cloning and functional analysis of the ubiquitin-specific protease gene UBP1 of Saccharomyces cerevisiae. 205 Jun 95

The baculovirus Autographa californica nuclear polyhedrosis virus (AcMNPV, which is representative of the MNPV subtype in which the virions may contain many nucleocapsids within a single viral envelope) encodes a protein, v-ubi, that has 76% identity with the eukaryotic protein ubiquitin. Transcriptional mapping indicated that the gene for v-ubi was transcribed during the late phase of viral infection. Two transcriptional start sites potentially encoding v-ubi were identified. Both sites were contained within a sequence motif common to baculovirus late genes. A recombinant virus, AcUbi-beta Gal, encoding a ubiquitin-beta-galactosidase fusion protein was constructed to monitor the temporal regulation of v-ubi gene during viral infection. The fusion protein was expressed maximally at 14-18 hr postinfection, consistent with its classification as a late protein. The amount of ubiquitin-beta-galactosidase fusion protein that accumulated in AcUbi-beta Gal-infected cells by 48 hr postinfection was approximately 14% of the level of beta-galactosidase that was synthesized under control of the polyhedrin promoter. Transcriptional analysis confirmed that synthesis of the fusion protein was directed by the v-ubi gene promoter. AcUbi-beta Gal also produced normal levels of authentic viral ubiquitin message. Southern blot analysis of AcUbi-beta Gal and 15 additional isolates revealed that the fusion sequences had not recombined at the ubiquitin locus. A polyubiquitin gene was isolated and sequenced from Spodoptera frugiperda, a lepidopteran host cell line for AcMNPV. The predicted amino acid sequence of the product of the host gene is identical to animal ubiquitin.
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PMID:Identification of a viral gene encoding a ubiquitin-like protein. 215

The chromosomal location of the human ubiquitin genes has been evaluated by in situ hybridization. Because of the conservation of the ubiquitin sequence, coding-region probes cannot distinguish between specific ubiquitin genes and reveal ubiquitin sequences in a number of different chromosomal regions. The major sites of hybridization with a coding-region probe include 17p11.1-p12, 12p24.2-q24.32, and 2q21-q24, with weaker hybridization over 1p3, 1q4, 2q3, and 13q. Hybridization with a probe isolated from the UbB gene intron indicated that this gene is located within the region 17p11.1-17p12. This region showed the strongest hybridization with the coding-region probe and is presumably also the location of the duplicated UbB pseudogene.
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PMID:Localization of the human UbB polyubiquitin gene to chromosome band 17p11.1-17p12. 215 95

Ubiquitin-conjugating enzymes catalyse the covalent attachment of ubiquitin to target proteins. Members of this enzyme family are involved in strikingly diverse cellular functions: UBC2 (RAD6) is central to DNA repair, UBC3 (CDC34) is involved in cell cycle control. We have cloned the genes for two novel ubiquitin-conjugating enzymes, UBC4 and UBC5, from the yeast Saccharomyces cerevisiae. These enzymes mediate selective degradation of short-lived and abnormal proteins. UBC4 and UBC5 are closely related in sequence and complementing in function. Expression of UBC4 and UBC5 genes is heat inducible. UBC4 and UBC5 enzymes generate high mol. wt ubiquitin-protein conjugates in vivo consistent with previous studies which suggested that attachment of multiple ubiquitin molecules to proteolytic substrates is required for their selective degradation. UBC4 and UBC5 enzymes comprise a major part of total ubiquitin-conjugation activity in stressed cells. Turnover of short-lived proteins and canavanyl-peptides but not of long-lived proteins is markedly reduced in ubc4ubc5 mutants. Loss of UBC4 and UBC5 activity impairs cell growth, leads to inviability at elevated temperatures or in the presence of an amino acid analog, and induces the stress response.
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PMID:Ubiquitin-conjugating enzymes UBC4 and UBC5 mediate selective degradation of short-lived and abnormal proteins. 215 73

Ubiquitin-protein conjugates are found by immunogold electron microscopy to be enriched (12-fold) in the lysosomal compartment of 3T3-L1 fibroblasts. Treatment of fibroblasts with the cysteine protease inhibitor E-64 leads to an expansion of the lysosomal compartment and as a result an increase in the cellular content of ubiquitin-protein conjugates. There is no change in the specific enrichment of ubiquitin-protein conjugates in the lysosomal compartment following E-64 treatment. The results suggest that some ubiquitin-protein conjugates may normally be degraded lysosomally following sequestration by microautophagy and imply that protein ubiquitination may be one of the signals for protein uptake into lysosomes.
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PMID:Ubiquitinated protein conjugates are specifically enriched in the lysosomal system of fibroblasts. 215 27

Senile plaques are present in the cerebellum of most Alzheimer patients. They are composed of beta-amyloid deposits lacking neurites detectable with immunocytochemistry for neurofilament, tau and paired helical filament proteins. Recent studies, however, have shown that cerebellar plaques usually contain round structures that are reactive with ubiquitin antibodies. In this immunoelectron microscopic study, the nature of these structures is explored. Ubiquitin-positive structures in cerebellar senile plaques were composed of degenerating neurites that contained membranous and vesicular dense bodies, but no paired helical filaments. A minority of the neurites contained finely granular material. Thus, cerebellar plaques are associated with neuritic degeneration, and the neurites in cerebellar plaques resemble dystrophic neurites in senile plaques of non-demented elderly subjects and subjects with non-Alzheimer dementias. They differ from some of the neurites in senile plaques in the neocortex in Alzheimer's disease by the absence of paired helical filaments. These results suggest that the same mechanisms involved in the generation of dystrophic neurites in pathological aging are involved in generating dystrophic neurites in the cerebellum in Alzheimer's disease.
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PMID:Ubiquitin immunoelectron microscopy of dystrophic neurites in cerebellar senile plaques of Alzheimer's disease. 215 1

Northern analysis demonstrated that levels of ubiquitin transcript increased during the chicken testis maturation process, in agreement with the previously published increase of ubiquitin during this differentiation process. Specific probes for four different ubiquitin genes (two polyubiquitins, UbI and UbII, and two ubiquitin-fusion genes, UbCep52 and UbCep80) allowed us to analyse the expression of each individual gene. UbI polyubiquitin gene was expressed in all the tissues tested, and its transcript was the most abundant ubiquitin RNA in all of them. Unspliced UbI transcript, already detected in stressed chicken-embryo fibroblast, was also present in immature testis and reticulocytes. UbII, a chicken polyubiquitin gene not previously found expressed and not heat-shock-inducible, was specifically stimulated during the testis maturation process. Two minor ubiquitin fusion transcripts of 0.6 and 0.7 kb, corresponding to UbCep52 and UbCep80 respectively, were also found in chicken testis. Although differentially expressed, it was found that UbI and UbII chicken polyubiquitin genes had an HTF ('HpaII tiny fragments') island (CpG-rich and constitutively unmethylated region) in their 5' proximal non-coding region. In addition, we demonstrated the coexistence of 3' and/or 5' relatively distal methylated sites together with these 5' proximal HTF islands in both chicken polyubiquitin genes. 3' and 5' distal UbI CCGG sites were specifically hypermethylated in mature testis, whereas a 3' distal UbII CCGG site was found to be about 50% methylated in all DNAs tested.
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PMID:Methylation of chick UbI and UbII polyubiquitin genes and their differential expression during spermatogenesis. 216 Feb 38

The highly conserved protein ubiquitin is synthesized in eukaryotes as two types of protein fusions from which active ubiquitin is derived by proteolytic processing. We report here the isolation and characterization of multiple genes from one type that encode ubiquitin extension proteins from the higher plant, Arabidopsis thaliana (L.). Two genes with 90% nucleotide identity in their exons encode ubiquitin and identical 52-amino acid (aa) extension proteins with 85 and 79% aa identity to 52-aa extension proteins from humans and yeast, respectively. Two other genes with 90% nucleotide identity encode ubiquitin and 81-aa extension proteins that differ by 4 amino acids from each other and are approximately 70% identical to the 76- and the 80-aa extension proteins from yeast and humans, respectively. Antibodies recognizing the 52- and 81-aa Arabidopsis extension proteins identify them as constituents of ribosomes. By sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the 52- and 81-aa extension proteins migrate at 6.8 and 11.5 kDa, respectively, and neither cross-reacts with anti-ubiquitin antibodies, indicating that extension proteins are cleaved from ubiquitin following translation. Ubiquitin extension protein genes encode the smallest transcript size class of ubiquitin mRNAs in Arabidopsis. The 5'-flanking regions of both UBQ1 and UBQ6, genes representative of the both extension proteins, direct the expression of readily detectable levels of the marker enzyme beta-glucuronidase in transgenic tobacco, suggesting the utility of these promoters for expression of foreign genes in higher plants.
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PMID:Ubiquitin extension proteins of Arabidopsis thaliana. Structure, localization, and expression of their promoters in transgenic tobacco. 216 66

Ubiquitin-immunoreactive structures in normal human brains ranging in age from 2 months to 91 years were studied with light and electron microscopy. Antibodies to ubiquitin immunostained structures in both neurons and glia. In the cerebrum, ubiquitin-immunoreactive, coarsely granular structures were most consistent with dystrophic neurites. They were most numerous in middle and upper cortical layers, especially lamina II of the entorhinal cortex and the cortical and accessory basal nuclei of the amygdala. Dystrophic neurites were first detected in brains of young adults, increased with age, and were numerous in the oldest brains. One of the normal elderly subjects had a small number of senile plaques with dystrophic neurites similar to those in the gray matter of the other brains, except for their location adjacent to amyloid deposits. With immunoelectron microscopy, dystrophic neurites were nonmyelinated neuronal processes containing dense, lamellar bodies, and finely granular material. White matter consistently had more immunoreactive structures than gray matter at all ages. The immunoreactive structures in white matter were smaller, less coarsely granular "dot-like" structures. With immunoelectron microscopy, dot-like structures were composed of dense inclusions within glial cells and focal swellings in myelin lamellae containing heterogeneous dense material. Only rarely were axons immunostained. Axonal spheroids in the basal ganglia, substantia nigra, and dorsal medulla were ubiquitin-immunoreactive. Spheroids were detected in these locations as early as the second decade, and they increased in number with age. A few dystrophic axons could be detected in spinal nerve roots of the oldest subjects. Other ubiquitin-immunoreactive structures included nuclei of small granular neurons, especially those in lamina II of the neocortex of the youngest brains; round cytoplasmic inclusions in tanycytes of all brains; and intranuclear Marinesco bodies in the substantia nigra and eosinophilic cytoplasmic inclusions in inferior olivary neurons in the oldest brains. These results demonstrate the spectrum of ubiquitinated structures in normal brains and suggest that progressive axonal dystrophy may be a more common age-related pathologic alteration of the brain than formerly recognized.
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PMID:Ubiquitin immunoreactive structures in normal human brains. Distribution and developmental aspects. 216 97


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