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)

Western blot analysis, using a polyclonal antibody to the 240-kDa endogenous inhibitor of the 20 S proteasome, revealed that the inhibitor is a component of the 26 S complex. Although isolated inhibitor displayed a single 40-kDa band on SDS-PAGE, the antibody detected a 55-kDa component in the 26 S proteasome complex. Ubiquitin polyclonal antibody recognized the same 55-kDa component but did not react with free 40-kDa inhibitor subunit. Addition of purified 40-kDa inhibitor to a ubiquitin ligating system also generated the 55-kDa species. In crude erythrocyte extracts, most of the inhibitor migrated at 55 kDa in the presence of ATP but shifted to 40 kDa in the absence of ATP, consistent with removal of ubiquitin. It is suggested that ubiquitination of the inhibitor may be involved in regulating assembly and/or activity of the 26 S proteasome complex.
Biochemistry 1992 Dec 08
PMID:Ubiquitinated proteasome inhibitor is a component of the 26 S proteasome complex. 133 90

Ubiquitin, an 8.5 kDa polypeptide found almost universally in plants and animals, is a normal component in the lens. The best documented function for ubiquitin involves its conjugation to proteins as a signal to initiate degradation. Conjugates for ubiquitin-dependent degradation tend to be of very high molecular mass and are rapidly degraded. Another role of ubiquitin conjugation may be as a stabilizer during stress for protection of constituent proteins, resulting in ubiquitin conjugates that are long-lived. Examination of clear and cataractous human lenses of < 1 to > 50 years revealed the dramatic accumulation of ubiquitin and ubiquitin conjugates with age, beginning at approximately 10 years. Epithelial tissue contained predominantly conjugates of > 250 kDa, although ubiquitin conjugates were found at 98 and 40-60 kDa in tissues from older donors. The water-soluble, urea-soluble and urea-insoluble fractions of lens cortex and core also contain ubiquitin conjugates that accrue with age. High molecular mass conjugates (> 250 kDa) are particularly prominent in older lens tissue. Cataractous lenses, as compared with normal lenses of the same age, show more of these high molecular mass conjugates in the urea-soluble and urea-insoluble fractions of cortex and core. Heterogeneous conjugates in the 20-85 kDa range accumulate in an age-related fashion in all lens cortex and core fractions. While levels of free ubiquitin are significant in the epithelium and the water-soluble cortex and core for all ages, there is no detectable free ubiquitin in the urea-soluble and urea-insoluble fraction under conditions used in this study.(ABSTRACT TRUNCATED AT 250 WORDS)
Exp Eye Res 1992 Dec
PMID:Ubiquitin and ubiquitin conjugates in human lens. 133 33

Proteasomes and ubiquitin (Ub) are essential components of the energy-dependent, nonlysosomal proteolytic pathway. To clarify the physiological role of this proteasome/Ub-dependent pathway, we meaured the levels of expressions of proteasomes and Ub in human renal cancers by Northern blot and immunochemical analyses. The mRNAs for two of the multiple subunits of proteasomes, C2 and C9, were expressed at abnormally high levels in most neoplastic lesions of patients with various primary renal cell carcinomas and in all renal cancer cell lines examined. However, no significant difference was found by enzyme immunoassay in the proteasomal contents of cancerous and normal parts of the kidney. The levels of mRNAs for the subunits of proteasomes were high in rapidly proliferating renal cells and appeared to be correlated with the activities of these cells for proteasome synthesis, but the cellular contents of proteasomes in these cells were normal, suggesting rapid turnover of proteasomes in rapidly proliferating cancer cells. Consistent with the increased expressions of proteasomal mRNAs, the expressions of three Ub genes, mono-UbA80, mono-UbA52, and poly-UbC, were found to be greatly increased in these renal cancer cells. Immunohistochemical staining of normal kidney showed that the levels of both proteasomes and Ub were high in cells of renal tubules and collecting ducts, but low in the glomerulus. The levels of both proteins appeared to be considerably increased in the nuclei of granular and clear carcinoma cells of the kidney. Moreover, the profiles of cellular proteins conjugated with Ub in normal kidney tissues were different from those in cancerous parts of the kidney and in established renal cancer cells. These results suggest that the proteasome- and ubiquitin-mediated system is functionally involved in the cancerous state in human kidney.
Cancer Res 1991 Dec 15
PMID:Changes in expressions of proteasome and ubiquitin genes in human renal cancer cells. 166 Mar 45

Ubiquitin carrier proteins (E2s) are involved in the covalent attachment of ubiquitin to a variety of cellular target proteins in eukaryotes. Here, we report the cloning of genes from wheat and Arabidopsis thaliana that encode 16-kDa E2s and a domain analysis of E2s by in vitro mutagenesis. The genes for E216kDa, which we have designated wheat and At UBC1, encode proteins that are only 33% identical (58% similar) with a 23-kDa E2 from wheat (encoded by the gene now designated wheat UBC4), but are 63% identical (82% similar) with the E2 encoded by the Saccharomyces cerevisiae DNA repair gene, RAD6. Unlike the proteins encoded by RAD6 and wheat UBC4, the UBC1 gene products lack acidic C-terminal domains extending beyond the conserved core of the proteins and are incapable of efficient in vitro ligation of ubiquitin to histones. From enzymatic analysis of the UBC1 and UBC4 gene products mutagenized in vitro, we have identified several domains important for E2 function, including the active site cysteine and N-terminal and C-terminal domains. Cysteine residues 88 and 85 in the UBC1 and UBC4 gene products, respectively, are necessary for formation of the ubiquitin-E2 thiol ester intermediate. Whereas the UBC1 gene product does not require its additional cysteine residue at position 116 for thiol ester formation, alteration of cysteine 143 in the UBC4 gene product greatly diminishes this ability. The N terminus of UBC1 contains two domains that affect activity: a proximal region containing hydroxylated and uncharged residues whose removal increases the rate of thiol ester formation and a distal tract rich in basic residues. Deletion or substitution of these basic residues with neutral residues diminishes the rate of thiol ester formation. We have demonstrated also that C-terminal extensions can function to confer substrate specificity to E2s. When the acidic extension was deleted from UBC4, the protein was unable to efficiently conjugate ubiquitin to histones in vitro. Furthermore, fusion of the UBC4 acidic extension to the C terminus of UBC1 resulted in a chimeric protein capable of efficient histone conjugation, as did fusion of short tracts of alternating aspartate and glutamate residues. This result suggests that the target protein specificity of E2s can be altered by the addition of appropriate C-terminal extensions, thus providing a way to modify the selectivity of the ubiquitin system.
J Biol Chem 1991 Dec 15
PMID:Cloning of a 16-kDa ubiquitin carrier protein from wheat and Arabidopsis thaliana. Identification of functional domains by in vitro mutagenesis. 166 Aug 87

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.
Brain Res 1991 Dec 06
PMID:Brain ubiquitin is markedly elevated in Alzheimer disease. 181 31

Radioiodinated histone H3 was incubated with ubiquitin, the ubiquitin-activating enzyme E1, and one of three ubiquitin carrier proteins, reticulocyte E2(20K) or E2(32K) or the yeast RAD6 product. Although the resulting ubiquitin-histone conjugates were synthesized in the absence of the substrate-binding protein E3, they were nevertheless degraded by purified rabbit reticulocyte 26 S protease. In contrast, unmodified histone H3 remained intact upon challenge with the 26 S ubiquitin/ATP-dependent enzyme. Conjugates produced by the RAD6 protein were better proteolytic substrates than those formed by reticulocyte E2 unless ubiquitin molecules with altered lysines were used for conjugate synthesis. Substitution of methylated ubiquitin or ubiquitin molecules in which lysine 48 was converted to arginine by site-directed mutation produced histone conjugates that were degraded at slow but measurable rates. Since methylated ubiquitin molecules are incapable of forming branched polyubiquitin chains, these results demonstrate that neither ubiquitin "trees" nor the substrate binding factor E3 is absolutely required for ubiquitin-dependent degradation of histone H3 in vitro.
J Biol Chem 1990 Dec 15
PMID:Ubiquitin-mediated degradation of histone H3 does not require the substrate-binding ubiquitin protein ligase, E3, or attachment of polyubiquitin chains. 217 83

A ubiquitin variant with Lys48 changed to Arg acts in vitro as an inhibitor of ubiquitin dependent protein degradation. To assess the role of this proteolytic pathway in the life cycle of plants, we expressed the ubiquitin variant in Nicotiana tabacum. Expression of variant mono- or polyubiquitin leads to marked abnormalities in vascular tissue. In addition, overexpression of variant polyubiquitin induces discrete lesions on leaves. This indicates that perturbations of the ubiquitin system can induce a programmed necrotic response in plants.
EMBO J 1990 Dec
PMID:Perturbation of the ubiquitin system causes leaf curling, vascular tissue alterations and necrotic lesions in a higher plant. 217 55

In eukaryotic cells ubiquitin is synthesized as a polyubiquitin protein or as a protein fused at the carboxyl terminus to other polypeptides. An enzyme activity, ubiquitin protein peptidase, has been proposed to process these precursors by cleaving the peptide bond between adjoining ubiquitin molecules or between ubiquitin and the fused peptides. Using the cleavage of a 35S-labeled yeast ubiquitin protein fused to a synthetic 38-residue peptide obtained by in vivo metabolic labeling in Escherichia coli in an expression system based on the interaction of bacteriophage T7 RNA polymerase and its promoter, it is possible to detect a processing activity in soluble yeast extract. The specificity of the cleavage suggests this activity could be the in vivo processing activity for various ubiquitin precursor proteins in yeast cells. A similarly labeled ubiquitin protein fused to one cysteine residue was also utilized to detect an activity capable of removing a single cysteine residue from ubiquitin in a soluble extract. Employing assays based on the cleavage of labeled ubiquitin protein fusions, a ubiquitin protein peptidase activity from Saccharomyces cerevisiae was purified about 15,000-fold to yield a protein mixture consisting of only a few protein species. The major protein band which comigrated with the activities in in vitro assays has an apparent molecular weight of 29,000 when analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Two other protein species, about 20,000 and 10,000 in molecular weight, also comigrated with the in vitro activities throughout the purification procedure. Though our most purified protein fraction was shown to cleave various artificial ubiquitin protein fusions under our experimental conditions, it cannot cleave a ubiquitin dimer protein, suggesting the existence of functionally distinct ubiquitin protein peptidases. Our experimental protocol for preparing various labeled ubiquitin protein precursors provides a means to explore various processing enzymes existing in cells. The same protocol may also be adapted to prepare substrates for the study of other specific protein processing enzymes.
J Biol Chem 1989 Dec 05
PMID:Purification of a ubiquitin protein peptidase from yeast with efficient in vitro assays. 255 55

Ubiquitin is a 76-amino-acid protein and is perhaps the most conserved gene product in evolution. It modulates degradation of abnormal or damaged proteins and belongs to the class of heat-shock proteins induced in conditions of cell stress. Recent work shows that ubiquitin is involved in several chronic degenerative diseases characterized by the formation of cellular inclusion bodies. The ubiquitin response to cell injury appears to be cytoprotective and particularly important in diseases of the nervous system.
Br J Hosp Med 1989 Dec
PMID:Ubiquitin: new insights into chronic degenerative diseases. 255 55

The genome of Tetrahymena pyriformis was shown to contain a ubiquitin multigene family consisting of at least four polyubiquitin genes. Three genomic clones with different ubiquitin-coding sequences, were isolated and partially characterized. The complete nucleotide sequence of one of these clones (pTU2) was determined and showed two open reading frames (ORFs) at opposite ends of the cloned DNA insert. A comparison of the predicted amino acid (aa) sequence of T. pyriformis ubiquitin-coding unit with those from other organisms indicated a high degree of homology. However, Tetrahymena ubiquitin contained two aa substitutions at positions 16 (Asp) and 19 (Ala). Interestingly, the first pTU2 ORF showed two extra triplets coding for Ser and Gln, upstream from TGA. This feature is different from all the polyubiquitin genes thus far sequenced. Regions flanking the 3' and 5' ubiquitin-coding sequences presented several conserved motifs. The 5' flanking sequence of the second ORF of pTU2 contained one heat-shock element. We therefore studied the expression of the ubiquitin genes under stress conditions. The results showed that they are heat-inducible and that a new specific 1.6-kb mRNA appeared. These results suggest that the regulation of ubiquitin genes is important in T. pyriformis under thermal stress conditions.
Gene 1988 Dec 15
PMID:Ubiquitin genes in Tetrahymena pyriformis and their expression during heat shock. 285 94


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