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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 such fundamental cellular processes as cell cycle control, DNA repair, protein degradation and stress responses. We previously reported that cisplatin could inhibit the ubiquitin-ATP-dependent proteolysis and ubiquitination. We further investigated the effect of various antitumor agents on the ubiquitin system and found that aclarubicin (ACR) inhibits the ubiquitin-ATP-dependent proteolysis but not the ubiquitination process. We found that ACR as well as cisplatin inhibited the ubiquitin-ATP-dependent proteolytic activity of rabbit reticulocytes. The IC50 values of these agents were 52 and 90 microM, respectively. Although cisplatin inhibits the conjugation of ubiquitin to proteins through the inhibition of a ubiquitin-activating enzyme, ACR, at 120 microM, does not. Thus, the antitumor agents affecting the ubiquitin system could be classified into two groups; one is represented by cisplatin, which inhibits the ubiquitination of the proteins, and the other is ACR, which does not inhibit the ubiquitination but does inhibit the ubiquitin-ATP-dependent proteolysis. Mitomycin C belongs to the latter group.
Biochim Biophys Acta 1992 Sep 15
PMID:Inhibition of different steps of the ubiquitin system by cisplatin and aclarubicin. 132 34

The fau gene is the cellular homolog of the fox sequence in the Finkel-Biskis-Reilly Murine Sarcoma Virus (FBR-MuSV). This virus acquired the fau sequence in its reversed transcriptional orientation. Human and mouse fau cDNA's were identified and both encode a new protein of 133 AA. We show that fau (for FBR-MuSV associated ubiquitiously expressed gene) becomes expressed in all different tissues tested as a 600 bp messenger and we report the genomic structure of the human fau gene. The gene consists of five exons and four introns and the 5' untranslated region displays characteristic features for a housekeeping gene. Fau encodes the ribosomal protein S30 fused to a Ubiquitin-like protein.
Biochem Biophys Res Commun 1992 Sep 16
PMID:Genomic structure and expression of the human fau gene: encoding the ribosomal protein S30 fused to a ubiquitin-like protein. 132 60

Two ubiquitin genes, designated UbB1 and UbB2, were isolated from a sunflower genomic library. They encode polyubiquitin transcripts corresponding to six repeats of the monomer. Northern blot analysis identified several different transcript size classes: both UbB1 and UbB2 transcripts are found in the most abundant 1.6 kb class. In contrast to the previously isolated UbF transcript which is present at high levels in flowers, UbB1 and UbB2 are expressed constitutively at low levels in different tissues. The levels of the two transcripts increase after heat stress. The two genes exhibit strong homology suggesting that they may result from duplication and conversion. Surprisingly, UbB1 gene shows structural similarities with the chicken ubiquitin heat shock gene, in particular the presence of an intron located just in front of the first ATG.
Plant Mol Biol 1991 Sep
PMID:Structure and expression of sunflower ubiquitin genes. 165 59

A derivative of ubiquitin in which amino groups were blocked by reductive methylation was used to study the possible role of the ubiquitin pathway in the cell cycle-programmed degradation of cyclin. It was shown previously that methylated ubiquitin can be efficiently ligated to protein substrates, but cannot form polyubiquitin chains. In the well-characterized ubiquitin-dependent proteolytic system from reticulocytes, it was found that rates of protein breakdown obtained with methylated ubiquitin are generally slower than those with ubiquitin; and thus, this derivative can be used, in some cases, as an inhibitor of ubiquitin-dependent protein degradation. The addition of methylated ubiquitin to a cell-free system from fertilized clam oocytes inhibited the degradation of both cyclins A and B. That this was due to specific interference with ubiquitin function was indicated by the observation that the supplementation of excess ubiquitin completely overcame the inhibitory action of methylated ubiquitin on cyclin degradation. These findings suggest that polyubiquitin chain formation is required for cyclin degradation.
J Biol Chem 1991 Sep 05
PMID:Methylated ubiquitin inhibits cyclin degradation in clam embryo extracts. 165 32

Ubiquitin-immunoreactivity was studied in Down's syndrome brains ranging in age from two days to sixty years. Numerous randomly distributed ubiquitin-immunoreactive dot-like structures in the white matter were shown to correspond to granular degeneration of myelin. Granular degeneration of myelin was first detected at age 21 and increased thereafter with age. Other larger and more coarsely granular ubiquitin-immunoreactive structures, most numerous in the middle and upper cortical layers, were consistent with dystrophic neurites. Immunoelectron microscopy demonstrated that the dystrophic neurites contained non-filamentous, membranous, dense bodies. In Down's syndrome, ubiquitin-immunoreactive dystrophic neurites were first detected at age six in the hippocampus, and were consistently more numerous in comparison to age-matched control subjects. In the presence of amyloid, either as diffuse or as compact deposits, ubiquitin-immunoreactive dystrophic neurites frequently formed aggregates consistent with senile plaques. Although apparently independent events, these data suggest that amyloid deposition is associated with local accentuation of ubiquitin-immunoreactive neuritic dystrophy. In addition, since dystrophic neurites appeared substantially earlier in the grey matter in Down's syndrome than in age-matched normals, this may be further evidence that selective aspects of aging are accelerated in Down's syndrome.
J Neuropathol Exp Neurol 1991 Sep
PMID:Ubiquitin-immunoreactive dystrophic neurites in Down's syndrome brains. 165 99

Ubiquitin is ubiquitous in all eukaryotes and its amino acid sequence shows extreme conservation. Ubiquitin genes comprise direct repeats of the ubiquitin coding unit with no spacers. The nucleotide sequences coding for 13 ubiquitin genes from 11 species reported so far have been compiled and analyzed. The G + C content of codon third base reveals a positive linear correlation with the genome G + C content of the corresponding species. The slope strongly suggests that the overall G + C content of codons of polyubiquitin genes clearly reflects the genome G + C content by AT/GC substitutions at the codon third position. The G + C content of ubiquitin codon third base also shows a positive linear correlation with the overall G + C content of coding regions of compiled genes, indicating the codon choices among synonymous codons reflect the average codon usage pattern of corresponding species. On the other hand, the monoubiquitin gene, which is different from the polyubiquitin gene in gene organization, gene expression, and function of the encoding protein, shows a different codon usage pattern compared with that of the polyubiquitin gene. From comparisons of the levels of synonymous substitutions among ubiquitin repeats and the homology of the amino acid sequence of the tail of monomeric ubiquitin genes, we propose that the molecular evolution of ubiquitin genes occurred as follows: Plural primitive ubiquitin sequences were dispersed on genome in ancestral eukaryotes. Some of them situated in a particular environment fused with the tail sequence to produce monomeric ubiquitin genes that were maintained across species. After divergence of species, polyubiquitin genes were formed by duplication of the other primitive ubiquitin sequences on different chromosomes. Differences in the environments in which ubiquitin genes are embedded reflect the differences in codon choice and in gene expression pattern between poly- and monomeric ubiquitin genes.
J Mol Evol 1991 Sep
PMID:Essential factors determining codon usage in ubiquitin genes. 166 81

The heat shock/stress response is characterized by the induction of several highly evolutionarily conserved proteins during thermal stress, chemical stress, or glucose starvation. It has recently been recognized that members of the stress protein family are synthesized constitutively and subserve functions that are critical to protein folding during intracellular transport. In this study we examined the expression of heat shock/stress proteins in human mononuclear phagocytes, cells dependent on intracellular transport for Ag processing, Ag presentation, generation of reactive oxygen intermediates, and secretion of proinflammatory and antiinflammatory polypeptides. The results indicate that there are distinct patterns in expression of individual members of the highly homologous SP70, SP90, and ubiquitin gene families during different stress states. There is a marked increase in expression of the heat-inducible form of SP70 and SP90 in human monocytes during heat shock. Expression of GRP 78/BiP and GRP 94 increases predominantly during glucose starvation but also increases during heat shock. Ubiquitin gene expression increases during both heat shock and glucose starvation. There is no change in synthesis of the constitutive form of SP 70 or of the ubiquitin activating enzyme E1 during heat shock or glucose starvation. Synthesis of the constitutive form of SP 70 and novel SP 90-like polypeptides increase during endotoxin-mediated inflammatory activation. One intracellular transport process of the mononuclear phagocyte, secretion of specific proinflammatory and antiinflammatory polypeptides, is affected by glucose starvation and by heat shock.
J Immunol 1991 Sep 01
PMID:Expression of stress proteins in human mononuclear phagocytes. 188 Apr 18

Ubiquitin is an extremely conserved protein, with an identical sequence throughout the animal kingdom. However, the gene sequence of the yeast protein [Ozkaynak, E., Finley, D., & Varshavsky, A. (1984) Nature (London) 312, 663-666] predicts three amino acid differences. This implies that some functions or binding interactions of ubiquitin are different in yeast and animal cells. In an effort to define these differences, ubiquitin has been purified to homogeneity from bakers' yeast and characterized. Amino acid analysis of the protein and the isolated tryptic peptides confirms the primary structure of this protein as predicted from the gene sequence. This result indicates that the gene sequenced is the transcriptionally active gene from yeast. The conformation of yeast ubiquitin is similar to human ubiquitin as judged by circular dichroism, sensitivity to trypsin, and Stokes radius. Yeast and animal ubiquitins show identical activities in supporting ubiquitin-dependent protein degradation and in the ATP-pyrophosphate exchange reaction catalyzed by the purified ubiquitin-adenylating enzyme. Thus, the three conservative amino acid differences between yeast and animal ubiquitins have very little effect on the structure of ubiquitin or its activity in the ubiquitin-dependent proteolytic system. These results suggest that at least some of the evolutionary pressure preventing sequence variation among animal ubiquitins stems from one or more of its nonproteolytic functions.
Biochemistry 1986 Sep 09
PMID:Structure and activities of a variant ubiquitin sequence from bakers' yeast. 302 Dec 9

Among eukaryotes studied to date, homologs of the yeast 76-amino acid ribosomal protein have invariably been found to be cotranslated with ubiquitin. However, in the nematodes Caenorhabditis elegans and Caenorhabditis briggsae, a 70-amino acid domain with only 40% identity to ubiquitin is cotranslated with a homolog of the ribosomal protein. In the nematode ubiquitin-like (UbL) proteins, the nucleotide sequence of the UbL coding region is 92% identical in C. elegans and C. briggsae. The corresponding gene sequence contains a single intron at a location identical to that found in the polyubiquitin gene of C. elegans, further confirming that the ubl genes are evolutionarily related to ubiquitin. The ribosomal protein portion of the UbL polypeptide consists of 93 amino acids and is 68% identical to the human homolog. The ribosomal protein portion of UbL is longer than in other homologs, with the additional sequence being present as a basic carboxyl extension. The ubl gene is constitutively expressed in all life cycle stages of C. elegans. A comparison of the nematode UbL sequences with other ubiquitin-like genes reveals a pattern of sequence conservation, which suggests that the ubiquitin-like proteins may have conserved functional domains.
J Biol Chem 1993 Sep 15
PMID:Novel ubiquitin-like ribosomal protein fusion genes from the nematodes Caenorhabditis elegans and Caenorhabditis briggsae. 769 36

Ubiquitin is a small highly conserved intracellular protein which is involved in a number of cellular functions including targeting proteins for degradation. We have studied the distribution of ubiquitin-protein conjugates and two enzymes involved in protein ubiquitination in chick embryos. Using immunocytochemical techniques, we have observed that chick neural crest cells and dorsal root ganglia acquire immunoreactivity in their nuclei and cytoplasm as they mature, both in vivo and in vitro, though they are not immunoreactive at early stages of development. Immunoreactivity for the ubiquitin activating enzyme (E1) and a carboxyl terminal hydrolase for ubiquitin (PGP 9.5) also appears in the nuclei of differentiating neurons at the same time as ubiquitin-protein conjugates. Our results provide evidence that the nuclear accumulation of ubiquitin-protein conjugates is closely associated with maturation of neurons towards a differentiated phenotype.
Brain Res Dev Brain Res 1994 Sep 16
PMID:Protein ubiquitination and neuronal differentiation in chick embryos. 781 39


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