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 a 76-amino acid protein whose sequence is highly conserved throughout evolution from invertebrates to mammals. It is both a cytoplasmic and nuclear protein. In the cytoplasm it is involved in ATP-dependent nonlysosomal proteolysis. In the nucleus, ubiquitin is conjugated to histone 2A and may play a role in regulation of chromatin structure and/or regulation of transcriptional activity. During attempts to identify a cDNA encoding somatomedin-C (insulin-like growth factor I) we screened a fetal human liver cDNA library with a mixture of 17 base oligonucleotides corresponding to a portion of the B chain of somatomedin-C. One oligonucleotide of the mixture hybridized to two cDNAs encoding ubiquitin despite a 2-base pair mismatch. Nucleotide sequence analyses of the 350- and 516-base pair cDNAs revealed that they correspond to the same ubiquitin mRNA. The coding sequence of the 516-base pair cDNA begins at amino acid 5 of the ubiquitin sequence and encodes amino acids 5 through 76 of ubiquitin, an 80-amino acid carboxy-terminal extension, a 3' untranslated region, and a poly(A) tail. The finding that ubiquitin is synthesized as a precursor raises the possibility that the precursor sequence may be important in compartmentalization of ubiquitin or ubiquitin precursors. Analyses of ubiquitin mRNAs in poly(A) RNA extracted from human liver and various rat tissues reveals that there are three distinct mRNAs encoding ubiquitin in humans and four mRNAs in the rat.
 ...
PMID:Nucleotide sequence analysis of a cDNA encoding human ubiquitin reveals that ubiquitin is synthesized as a precursor. 258 67

A human erythroleukemia cell line, K-562 T1, was adapted to a protein-free chemically defined medium; that is, the medium does not contain any proteins such as exogenous hormones, growth factors, serum and serum albumin. The K-562 T1 cells which can proliferate in a protein-free medium are one of the model systems suitably supporting the autocrine hypothesis, which claims that cancer cells produce and respond to their own growth factors. The K-562 T1 cells were cultured in a protein-free medium at large scale and the growth factors were purified from the conditioned medium. It was found that K-562 T1 cells produce at least two growth factors; one is LGF-I (leukemia-derived growth factor-I) which can stimulate the proliferation of a wide range of human leukemia cell lines and the other is LGF-II (leukemia-derived growth factor-II), which can contribute to the growth of fibroblasts. LGF-I was purified using QAE-Sephadex, Bio Gel P-60 and Mono S FPLC. The purified protein was found to be homogenous by SDS-polyacrylamide gel electrophoresis and NH2-terminal sequence analysis. The molecular weight of LGF-I was 20,000 by SDS-polyacrylamide gel electrophoresis. The 30 NH2-terminal residues of LGF-I are the same as that of ubiquitin. Ubiquitin is a protein found in eukaryotic cells with molecular weight of 8,600. In the nucleus ubiquitin is conjugated to histone 2A to form the nuclear protein A24 which may play a role in regulation of chromatin structure, and in the cytoplasm is part of an ATP-dependent non-lysosomal proteolytic pathway. However, its physiological significance has not yet been fully resolved. Ubiquitin purified from bovine thymus did not show cell proliferating activity for any cells tested. The results suggest that LGF-I is a new autocrine growth factor with a molecular weight of 20,000 daltons, containing ubiquitin at the NH2-terminal end.
 ...
PMID:N-terminal amino acid sequence of leukemia derived growth factor (LGF) from human erythroleukemia cell culture. 303 91

Ubiquitin-dependent proteolysis of specific target proteins is required for several important steps during the cell cycle. Degradation of such proteins is strictly cell cycle-regulated and triggered by two large ubiquitin ligases, termed anaphase-promoting complex (APC) and Skp1/Cullin/F-box complex (SCF). Here we show that yeast Ran-binding protein 1 (Yrb1p), a predominantly cytoplasmic protein implicated in nucleocytoplasmic transport, is required for cell cycle regulated protein degradation. Depletion of Yrb1p results in the accumulation of unbudded G(1) cells and of cells arrested in mitosis implying a function of Yrb1p in the G(1)/S transition and in the progression through mitosis. Temperature-sensitive yrb1-51 mutants are defective in APC-mediated degradation of the anaphase inhibitor protein Pds1p and in degradation of the cyclin-dependent kinase inhibitor Sic1p, a target of SCF. Thus, Yrb1p is crucial for efficient APC- and SCF-mediated proteolysis of important cell cycle regulatory proteins. We have identified the UBS1 gene as a multicopy suppressor of yrb1-51 mutants. Ubs1p is a nuclear protein, and its deletion is synthetic lethal with a yrb1-51 mutation. Interestingly, UBS1 was previously identified as a multicopy suppressor of cdc34-2 mutants, which are defective in SCF activity. We suggest that Ubs1p may represent a link between nucleocytoplasmic transport and ubiquitin ligase activity.
 ...
PMID:Yeast Ran-binding protein Yrb1p is required for efficient proteolysis of cell cycle regulatory proteins Pds1p and Sic1p. 1099 51

Ubiquitin-dependent protein degradation impacts many cellular processes.However, the regulation of ubiquitin-conjugating enzymes (UBCs) in cancer is unknown. We find that the human CDC34 UBC protein is expressed at a 3-4 fold higher level (P < 0.001) in pediatric T cell than in pre-B-cell acute lymphoblastic leukemia (ALL) before treatment in two independent patient sets. The level of CDC34 mRNA was similar in both types of leukemia. CDC34 expression levels in normal resting T cells, B cells and activated T lymphocytes was comparable with pre-B-cell ALL. CDC34 protein (but not mRNA) was also increased in T-cell ALL compared with pre-B-cell ALL cell lines. The difference in expression was not attributable to mutation or associated with altered CDC34 stability. Immunohistochemistry and cellular fractionation reveals a heterogeneous CDC34 expression pattern including cells containing primarily cytoplasmic or nuclear protein. Thus, a feature of pediatric T-cell ALL is posttranscriptional up-regulation and heterogeneous localization of the human CDC34 UBC.
 ...
PMID:Expression and localization of the CDC34 ubiquitin-conjugating enzyme in pediatric acute lymphoblastic leukemia. 1150 8

In Galleria mellonella, the pupal-adult transformation of epidermal cells is initiated at day 1 after pupal ecdysis by downregulation of pupal syntheses and loss of juvenile hormone (JH) sensitivity, indicating the change from pupal to adult commitment. To trace regulatory events as close as possible to the early steps of this process, we have analyzed, by differential display, changes in epidermal mRNA populations during the first day after pupal ecdysis in normal development as well as after JH injection. We isolated and cloned 20 cDNA 3'-fragments that are differentially expressed with regard to their developmental profile either in normal development or after injection of JH. Four clones could be verified by Northern blot hybridization. Screening of corresponding cDNA libraries with digoxigenin-labeled anti-sense mRNA probes yielded two full-length cDNA clones (9/27 and 23/86). Both of them represent genes that could be involved in the regulatory events during initiation of pupal metamorphosis or in the action of JH, respectively. The 9/27 mRNA is inducible by JH. It contains, in the 3' untranslated region, a consensus sequence for deadenylation and specific degradation. The corresponding protein possesses two PKC phosphorylation sites and is with high probability a nuclear protein. The 23/86 clone represents polyubiquitin, differentially regulated in normal development and after JH application.
 ...
PMID:Differentially expressed genes in metamorphosis and after juvenile hormone application in the pupa of Galleria. 1175 54

Glucocorticoid hormones (GCs) exert a potent anti-proliferative activity on several cell types. The classic molecular mechanism of GCs involves modulation of the activity of the glucocorticoids receptor, a transcriptional regulator. However, the anti-proliferative effect of GCs may also involve modulation of processes such as translation, subcellular localization and post-translational modifications, which are not reflected at the mRNA level. To investigate these potential effects of GCs, we employed the proteomic approach (two-dimensional electrophoresis and mass spectrometry) and the ST1 cells, obtained from the C6 rat glioma cell line, as a model. GC treatment leads ST1 cells to a complete transformed-to-normal phenotypic reversion and loss of their tumorigenic potential. By comparing sets of 2D nuclear protein profiles of ST1 cells treated (or not) with hydrocortisone (Hy), 13 polypeptides displaying >or=two-fold difference in abundance upon Hy treatment were found. Five of these polypeptides were identified by peptide mass fingerprinting, including Annexin 2 (ANX2), hnRNP A3 and Ubiquitin. Evidence obtained by Western blot analysis indicates that ANX2 is present in the nucleus and has its subcellular localization modulated by GC-treatment of ST1 cells. Our findings indicate complementary mechanisms contributing to the regulation of gene expression associated with ST1 cells' response to GCs.
 ...
PMID:Differential proteomic analysis of the anti-proliferative effect of glucocorticoid hormones in ST1 rat glioma cells. 1712 50

Fifty-six nuclear protein coding genes from Taxonomically Broad EST Database and other databases were selected for phylogenomic-based examination of alternative phylogenetic hypotheses concerning intergroup relationship between multicellular animals (Metazoa) and other representatives of Opisthokonta. The results of this work support sister group relationship between Metazoa and Choanoflagellata. Both of these groups form the taxon Holozoa along with the monophyletic Ichthyosporea or Mesomycetozoea (a group that includes Amoebidium parasiticum, Sphaeroforma arctica, and Capsaspora owczarzaki). These phylogenetic hypotheses receive high statistical support both when utilizing whole alignment and when only 5000 randomly selected alignment positions are used. The presented results suggest subdivision of Fungi into Eumycota and lower fungi, Chytridiomycota. The latter form a monophyletic group that comprises Chytridiales+Spizellomycetales+Blastocladiales (Batrachochytrium, Spizellomyces, Allomyces, Blastocladiella), contrary to the earlier reports based on the analysis of 18S rRNA and a limited set of protein coding genes. The phylogenetic distribution of genes coding for a ubiquitin-fused ribosomal protein S30 implies at least three independent cases of gene fusion: in the ancestors of Holozoa, in heterotrophic Heterokonta (Oomycetes and Blastocystis) and in the ancestors of Cryptophyta and Glaucophyta. Ubiquitin-like sequences fused with ribosomal protein S30 outside of Holozoa are not FUBI orthologs. Two independent events of FUBI replacement by the ubiquitin sequence were detected in the lineage of C. owczarzaki and in the monophyletic group of nematode worms Tylenchomorpha+Cephalobidae. Bursaphelenchus xylophilus (Aphelenchoidoidea) retains a state typical of the rest of the Metazoa. The data emphasize the fact that the reliability of phylogenetic reconstructions depends on the number of analyzed genes to a lesser extent than on our ability to recognize reconstruction artifacts.
 ...
PMID:Do we need many genes for phylogenetic inference? 1820 15

SUMO (Small Ubiquitin-like MOdifier) conjugation is a post-translational modification implicated in a variety of cellular functions including transcriptional regulation, nuclear location and signal transduction. Sumoylation, although conserved and vital in eukaryotes, has not been studied in malaria parasites. Here, we identify SUMO conjugation of blood stage parasites of Plasmodium falciparum. Antibodies raised against synthetic peptides of the plasmodial SUMO orthologue PfSUMO, a 100-amino-acid protein, reacted with distinctive subcellular compartments of the parasitized erythrocyte during blood stage development. Anti-PfSUMO stains the nucleus and parasite cytoplasm. We also found antibody reactivity in the host cell cytoplasm with the parasite-derived structures called Maurer's clefts. Anti-PfSUMO reacts in Western blot with a number of blood stage proteins ranging from approximately 40-250 kDa. Parasites expressing FLAG-tagged PfSUMO gave similar results in Immunofluorescence assay and Western blots. In addition, we show that anti-PfSUMO identified PfSir2, a telomere-associated nuclear protein involved in var gene silencing, as a target for sumoylation. Furthermore, LC-MS/MS analysis of a two-step immunoprecipitation (IP) with anti-FLAG and anti-PfSUMO antibodies reveals a number of putative P. falciparum sumoylated proteins. Our results imply that SUMO conjugation has an essential function in a number of different biological processes in P. falciparum.
 ...
PMID:Identification of a novel post-translational modification in Plasmodium falciparum: protein sumoylation in different cellular compartments. 1854 37

Grain weight is a major determinant of crop grain yield and is controlled by naturally occurring quantitative trait loci (QTLs). We earlier identified a major QTL that controls rice grain width and weight, GW5, which was mapped to a recombination hotspot on rice chromosome 5. To gain a better understanding of how GW5 controls rice grain width, we conducted fine mapping of this locus and uncovered a 1 212-bp deletion associated with the increased grain width in the rice cultivar Asominori, in comparison with the slender grain rice IR24. In addition, genotyping analyses of 46 rice cultivars revealed that this deletion is highly correlated with the grain-width phenotype, suggesting that the GW5 deletion might have been selected during rice domestication. GW5 encodes a novel nuclear protein of 144 amino acids that is localized to the nucleus. Furthermore, we show that GW5 physically interacts with polyubiquitin in a yeast two-hybrid assay. Together, our results suggest that GW5 represents a major QTL underlying rice width and weight, and that it likely acts in the ubiquitin-proteasome pathway to regulate cell division during seed development. This study provides novel insights into the molecular mechanisms controlling rice grain development and suggests that GW5 could serve as a potential tool for high-yield breeding of crops.Cell Research (2008) 18:1199-1209. doi: 10.1038/cr.2008.307; published online 18 November 2008.
 ...
PMID:Isolation and initial characterization of GW5, a major QTL associated with rice grain width and weight. 1901 68

Chfr, a checkpoint with FHA and RING finger domains, plays an important role in cell cycle progression and tumor suppression. Chfr possesses the E3 ubiquitin ligase activity and stimulates the formation of polyubiquitin chains by Ub-conjugating enzymes, and induces the proteasome-dependent degradation of a number of cellular proteins, including Plk1 and Aurora A. While Chfr is a nuclear protein that functions within the cell nucleus, how Chfr is localized in the nucleus has not been clearly demonstrated. Here, we show that nuclear localization of Chfr is mediated by nuclear localization signal (NLS) sequences. To reveal the signal sequences responsible for nuclear localization, a short lysine-rich stretch (KKK) at amino acid residues 257-259 was replaced with alanine, which completely abolished nuclear localization. Moreover, we show that nuclear localization of Chfr is essential for its checkpoint function but not for its stability. Thus, our results suggest that NLS-mediated nuclear localization of Chfr leads to its accumulation within the nucleus, which may be important in the regulation of Chfr activation and Chfr-mediated cellular processes, including cell cycle progression and tumor suppression.
 ...
PMID:Nuclear localization of Chfr is crucial for its checkpoint function. 1932 84


1 2 Next >>