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)

The effects of synthetic thymopoeitin32-36 and purified ubiquitin, in daily doses of 1 or 10 microgram, were studied in New Zealand mice. The most striking result was a 4-month delay in the appearance of Coombs' positive tests or Coombs' antibodies in New Zealand black (NZB) mice treated from 4 wk of age with ubiquitin. Ubiquitin also reduced the spleen weight in the animals and stimulated suppressor T cell activity in shorter term studies of older NZB and black and white (B/W) mice. Thymopoietin was also active in this assay and improved the mitogen responsiveness of lymph node cells in older treated NZB and B/W mice. Thymopoietin injections, from 4 wk of age, reduced the titer of Coombs' antibodies and thymocytotoxic antibodies in NZB mice and caused an increase in Thy 1+ spleen cells in these animals. In correspondingly treated B/W mice, thymopoietin reduced the anti-DNA antibody titer. While our present injection protocol did not result in clinical cure of the genetically determined autoimmune diseases of NZB and B/W mice, they do point to the feasibility of selective immunoregulation by these peptides in diseases associated with altered states of immune reactivity.
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PMID:The effect of thymopoietin32-36 and ubiquitin on spontaneous immunopathology of New Zealand mice. 31 25

A mouse ubiquitin clone that recognizes multiple transcripts overexpressed in murine tumors compared to normal epidermis was isolated by differential screening of complementary DNA libraries from mouse squamous cell carcinomas. Coding region probes detected five ubiquitin transcripts. Oligonucleotides were designed for unique parts of three mouse ubiquitin gene complementary DNA clones. The overexpressed transcripts at 2.4, 2.8, 6.4, and 7.8 kilobases (kb) were detected by an oligonucleotide specific for a mouse UbC polyubiquitin clone. A 1.2-kb UbB overexpressed transcript was detected by an oligonucleotide for a mouse four-unit polyubiquitin, and a 0.7-kb UbA overexpressed transcript was recognized by an oligonucleotide for the mouse ubiquitin carboxyl-extension protein of 52 amino acids. All three classes of transcripts were induced in mouse skin by the hyperproliferative agent ethylphenyl propionate and by the tumor promoting agent 12-O-tetradecanoylphorbol-13- acetate. Heat shock of cultured keratinocytes induced both the 6.4- and 7.8-kb transcripts recognized by the UbC-specific oligonucleotide. Consistent with the overexpression of the ubiquitin transcripts, the level of free ubiquitin protein, as determined by Western analysis, was elevated in the tumors and proliferating epidermis as compared to normal epidermis. Our results indicate that the overexpression of ubiquitin genes could be related to a sustained state of proliferation and stress in the tumors compared to the normal resting epidermis.
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PMID:Overexpression of three ubiquitin genes in mouse epidermal tumors is associated with enhanced cellular proliferation and stress. 132 56

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.
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PMID:Inhibition of different steps of the ubiquitin system by cisplatin and aclarubicin. 132 34

We have characterized a second T. brucei polyubiquitin gene (UbB) that is highly similar in the coding and flanking regions to a previously described T. brucei polyubiquitin gene (UbA). However, UbB differs from UbA in 2 respects: (1) the predicted carboxy-terminal amino acid of UbB is methionine, as opposed to leucine in UbA, and (2) UbB contains approximately 13 ubiquitin repeats, as opposed to approximately 30 repeats in UbA. In Southern blots of intact T. brucei DNA separated by pulsed field gel electrophoresis, the polyubiquitin sequences have been shown to reside on band 19, which may contain 3 chromosomes. Three experiments that target a neomycin-resistance gene to the polyubiquitin locus demonstrate a one-to-one ratio of polyubiquitin 3-flanking sequences, which suggests that UbA and UbB are alleles rather than duplications. Four additional strains of T. brucei and one strain of T. equiperdum show variation in their polyubiquitin gene size, suggesting that this is a common polymorphism.
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PMID:Allelic polymorphism of the Trypanosoma brucei polyubiquitin gene. 133 86

There are three species of ubiquitin gene transcripts in HeLa cells, termed UbA (approximately 0.7 kb), UbB (approximately 1.1 kb) and UbC (approximately 2.5 kb). In the present report, the UbC transcript was shown to accumulate up to 2.5-fold after irradiation with UV light or treatment with the phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA). The kinetic analysis indicated that the induced accumulation of UbC was rapid and transient; maximal accumulation of UbC was induced at 2.5 h after UV irradiation or 3 h after TPA treatment. Inhibition of a de novo protein synthesis by cycloheximide did not repress the induction of UbC after treatment with UV light and TPA. On the other hand, induction of UbA and UbB, in most cases, was not observed. UV-inducibility of human ubiquitin conjugating enzyme, E2(17k), was also tested. E2(17k) is a protein with high sequence similarity to the product of yeast DNA repair gene, RAD6. While the RAD6 gene has been reported to be inducible by UV light, no change in E2(17k) gene transcript was observed after UV irradiation.
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PMID:Induced accumulation of polyubiquitin gene transcripts in HeLa cells after UV-irradiation and TPA-treatment. 135 8

The hypotrichous ciliate, Euplotes eurystomus, contains both a transcriptionally inactive micronucleus (MIC) and a transcriptionally active macronucleus (MAC) in the same cell. MAC DNA is small (0.5-20 kb), linear and highly amplified. Each DNA fragment consists of two telomeres, a single coding region, and the necessary control elements to regulate gene transcription and replication. The polyubiquitin gene consists of 898 bp, plus 28 bp of double-stranded and 14 bases of single-stranded DNA of the telomeric repeat G4T4 at each end. The coding region exists as three copies of the ubiquitin gene (690 bp) fused in a head-to-tail arrangement as in other organisms. The stop codon is TAA, as in other Euplotes genes, and is not the rare glutamine codon used in most other ciliates. The 3' nontranslated region contains two presumptive poly(A) addition sites; the 5' nontranslated region possesses two putative TATA boxes, several imperfect direct and inverted repeats, and a possible origin of replication. Nucleosome positioning studies reveal four tightly packed nucleosomes and a non-nucleosomal area containing the probable 5' control region as well as part of the coding region. The 5' area does not contain any DNAse I hypersensitive sites. Although the telomeres are protected from exonuclease digestion, they are not as well protected as Oxytricha telomeres against endonucleases and cleavage by methidium propyl Fe2+ EDTA.
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PMID:Structure of the macronuclear polyubiquitin gene in Euplotes. 165 39

Cells of Chlamydomonas reinhardtii were synchronized by a light/dark illumination cycle of 14:10 h. All cells divided within the first 2 h of the dark period, the synchronization index was calculated as 0.916. RNA was isolated every 2 h and hybridized to 32P-labeled probes encoding (i) ubiquitin from Chlamydomonas reinhardtii (UBM) and (ii) two different ubiquitin-conjugating enzymes from Saccharomyces cerevisiae (UBC2 and UBC3). Sequences with homology to yeast UBC2 and UBC3, which are required for sporulation/DNA repair and G1/S transition in yeast, respectively, were detected in C. reinhardtii. In the algae, the relative abundance of transcripts encoding ubiquitin fusion proteins and UBC2 homologues is most prominent at the end of the light phase and throughout the dark. The highest amount of a putative polyubiquitin encoding transcript was detected during the dark phase of the synchronized culture. A high amount of this transcript is also present during the 8th hour of the light phase which may imply that the transcription of polyubiquitin gene is not only restricted to stress conditions in C. reinhardtii. The relative abundance of transcripts with homology to UBC3 is most pronounced within the light period corresponding to G1 and S phases of the C. reinhardtii cell cycle.
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PMID:Ubiquitin-encoding mRNA and mRNA recognized by genes encoding ubiquitin-conjugating enzymes are differentially expressed in division-synchronized cultures of Chlamydomonas reinhardtii. 165 8

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.
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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

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.
DNA Seq 1991
PMID:The macronuclear polyubiquitin gene of the ciliate Tetrahymena pyriformis. 166 85

Ubiquitin (Ubi) genes encode two types of fusion proteins: polyUbi with a varying number of direct repeats of Ubi, and Ubi-tail fusions with long or short basic C-terminal extensions. A barley (Hordeum vulgare) genomic clone has been isolated with two very similar, intronless genes encoding monoUbi-long-tail fusion peptides. The genes are arranged as direct repeats separated by 3 kb of DNA and account for two of the probable three long-tail genes in the haploid barley genome. Both genes are active and give rise to messengers about 800 nt long. The sequence of the encoded Ubi moieties is identical to the sequence of Ubi repeats of polyUbi precursors from barley and other plants. The basic tails of the peptides are 79 aa long and 71-72% homologous to corresponding sequences from yeast and man. Recently, it was found that the long and short tails are ribosomal proteins in yeast [Finley et al., Nature 338 (1989) 394-401] and the evolutionary conservation of the structure of the Ubi-tail fusion genes suggests that they serve the same function in plants. The similarity between yeast and barley Ubi-long-tail fusion genes may extend to the regulatory regions, since upstream activating sites characteristic of ribosomal protein-encoding genes in yeast (UASrpg) were found in the barley genes.
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PMID:Two ubiquitin-long-tail fusion genes arranged as closely spaced direct repeats in barley. 170 48


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