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)

We isolated and characterized two related ubiquitin genes from Drosophila melanogaster, polyubiquitin and UB3-D. The polyubiquitin gene contained 18 repeats of the 228-base-pair monomeric ubiquitin-encoding unit arranged in tandem. This gene was localized to a minor heat shock puff site, 63F, and it encoded a constitutively expressed 4.4-kilobase polyubiquitin-encoding mRNA, whose level was induced threefold by heat shock. To investigate the pattern of expression of the polyubiquitin gene in developing animals, a polyubiquitin-lacZ fusion gene was introduced into the Drosophila genome by germ line transformation. The fusion gene was expressed at high levels in a tissue-general manner at all life stages assayed. The ubiquitin-encoding gene, UB3-D, consisted of one ubiquitin-encoding unit directly fused, in frame, to a nonhomologous tail sequence. The amino acid sequence of the tail portion of the protein had 65% positional identity with that of yeast UBI3 protein, including a region that contained a potential nucleic acid-binding motif. The Drosophila UB3-D gene hybridized to a 0.9-kilobase mRNA that was constitutively expressed, and in contrast to the polyubiquitin gene, it was not inducible by heat shock.
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PMID:Structure and expression of ubiquitin genes of Drosophila melanogaster. 246 65

The authors have shown previously that ubiquitin, a protein involved in the degradation of short-lived and abnormal proteins, is present in several cytoplasmic inclusions of neurons. This study used a library of antibodies to ubiquitin and immunohistochemically examined for the presence of ubiquitin in nonviral intracytoplasmic inclusions that form in different cell types under various pathologic conditions. Membrane-bound lysosomal and nonlysosomal inclusions such as those of storage disease, Russell bodies, alpha-1-antitrypsin and alpha-fetoprotein as well as nonmembrane-bound inclusions were examined. Ubiquitin epitopes were detected in some of the nonmembrane-bound inclusions only. The ubiquitin-containing inclusions were the Rosenthal fibers, Mallory bodies, Crooke bodies, Lafora bodies, amyloid bodies, and the giant axons of giant axonal neuropathy. Nemaline bodies and the inclusions of juvenile digital fibromatosis, both of which contain actin and actinbinding proteins, did not show immunoreaction. These findings, as well as those of the previous study, show that the presence of ubiquitin in cellular inclusions is selective. The ubiquitin-containing inclusions are not membrane bound; they are fibrillary and most contain also intermediate filament-related proteins. The role of ubiquitin in the formation of these inclusions remains to be elucidated.
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PMID:Selective presence of ubiquitin in intracellular inclusions. 246 1

Histological sections of cerebral motor cortex, brainstem, and spinal cord from 10 cases of clinically diagnosed motor neurone disease (MND) and 10 control cases were examined by conventional histology and immunocytochemical methods to localise ubiquitin. Intracytoplasmic inclusion bodies were identified in motor neurones of hypoglossal nuclei and appeared specific for MND. Similar inclusions were found in both large pyramidal cells and small neurones in the motor cortex, and were restricted to 4 cases having the amyotrophic lateral sclerosis form of MND with severe degeneration of corticospinal tracts. As reported in earlier studies, cellular inclusion bodies were identified in motor neurones of spinal cord from cases of MND but not in control material. Ubiquitin inclusions in motor neurones appear to be markers for the degenerative process causing neuronal loss in MND and there appears to be a close association between the anatomical location of inclusions and clinical manifestations of disease.
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PMID:Inclusion bodies in motor cortex and brainstem of patients with motor neurone disease are detected by immunocytochemical localisation of ubiquitin. 248 32

Ubiquitin mRNA was found to be an abundant transcript which was induced by heat shock (HS), and certain other stresses in mammalian cells. In Chinese hamster cells, the 2 major ubiquitin transcripts of 2.6 kb and 1.7 kb were induced coordinately, while a minor ubiquitin transcript of 0.8 kb was not induced; the response was similar in human cells with induction of the 2.5 kb Ub C and 1.0 kb Ub B transcripts. A representative ubiquitin cDNA clone, isolated from a cDNA library derived from HS-treated Chinese hamster cells, coded for a typical tandem repeat polyubiquitin transcript. Only a portion of the 5' nontranslated sequence of this clone had homology with the previously published corresponding region in human Ub B mRNA. Oligonucleotide probes complementary to the portion of the 5' nontranslated sequence with homology to the human sequence and also portions with no homology hybridized only to the 1.7 kb transcript. There was coordinate induction of ubiquitin, HSP27, and HSP70 mRNA by HS as determined by both increased RNA and increased transcription. Ubiquitin mRNA was induced by certain DNA damaging agents, in particular the alkylating agent methylmethane sulfonate, or incubation in isoleucine-deficient medium under conditions where the other HSP mRNA were not.
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PMID:Ubiquitin mRNA is a major stress-induced transcript in mammalian cells. 253 50

Ubiquitin is a multifunctional 76-amino-acid protein which plays critical roles in many aspects of cellular metabolism. In Caenorhabditis elegans, the major source of ubiquitin RNA is the polyubiquitin locus, UbiA. UbiA is transcribed as a polycistronic mRNA which contains 11 tandem repeats of ubiquitin sequence and possesses a 2-amino-acid carboxy-terminal extension on the final repeat. The UbiA locus possesses several unusual features not seen in the ubiquitin genes of other organisms studied to date. Mature UbiA mRNA acquires a 22-nucleotide leader sequence via a trans-splicing reaction involving a 100-nucleotide splice leader RNA derived from a different chromosome. UbiA is also unique among known polyubiquitin genes in containing four cis-spliced introns within its coding sequence. Thus, UbiA is one of a small class of genes found in higher eucaryotes whose heterogeneous nuclear RNA undergoes both cis and trans splicing. The putative promoter region of UbiA contains a number of potential regulatory elements: (i) a cytosine-rich block, (ii) two sequences resembling the heat shock regulatory element, and (iii) a palindromic sequence with homology to the DNA-binding site of the mammalian steroid hormone receptor. The expression of the UbiA gene has been studied under various heat shock conditions and has been monitored during larval moulting and throughout the major stages of development. These studies indicate that the expression of the UbiA gene is not inducible by acute or chronic heat shock and does not appear to be under nutritional or developmental regulation in C. elegans.
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PMID:UbiA, the major polyubiquitin locus in Caenorhabditis elegans, has unusual structural features and is constitutively expressed. 253 20

In vivo, ubiquitin exists both free and conjugated through its carboxyl terminus to the alpha- and epsilon-amino groups of a wide variety of cellular proteins. Ubiquitin carboxyl-terminal hydrolytic activity is likely a necessary step in the regeneration of the ubiquitin cofactor from ubiquitin-protein conjugates. In addition, this type of activity is required to generate the active, monomeric ubiquitin from the only known gene products: the polyprotein precursor and various ubiquitin fusion proteins. Thus, this activity is of vital importance to systems that utilize ubiquitin as a cofactor. A generic substrate, ubiquitin ethyl ester, was previously developed [Wilkinson, K. D., Cox, M. J., Mayer, A. N., & Frey, T. (1986) Biochemistry 25, 6644-6649] and utilized here to monitor the fractionation of these activities from calf thymus. By use of a rapid HPLC assay, four distinct, ubiquitin-specific esterases were identified and separated. A previously undescribed activity has been resolved and characterized, in addition to the bovine homologue of ubiquitin carboxyl-terminal hydrolase purified from rabbit reticulocytes. Two other activities resemble deconjugating activities previously detected in crude extracts but not previously purified. These activities appear to form a family of mechanistically related hydrolases. All four activities are inhibited by iodoacetamide, indicating the presence of an essential thiol group, and are inhibited to various extents by manganese. All have specific ubiquitin binding sites as judged by the low observed Km values (0.6-30 microM). The carboxyl-terminal aldehyde of ubiquitin is a potent inhibitor of these enzyme activities, with Ki values approximately 1000-fold lower than the respective Km values.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Detection, resolution, and nomenclature of multiple ubiquitin carboxyl-terminal esterases from bovine calf thymus. 253 53

Immunocytochemical localization of the cell stress-associated protein ubiquitin was performed on human lesions containing Rosenthal fibres. Ubiquitin was localized around the periphery of classical Rosenthal fibres but not in the amorphous central areas; the ubiquitin-positive regions corresponded to the immunocytochemical localization of glial fibrillary acidic protein (GFAP). Compact bundles of GFAP in glial processes without a non-staining core were also associated with ubiquitin, while loosely aggregated cellular GFAP was not. The relationship between compact bundles of GFAP and the amorphous osmiophilic central component of Rosenthal fibres has been uncertain. These data, however, show that the compact bundles of glial filaments are distinct from normal GFAP in being associated with ubiquitin. A role for ubiquitin in Rosenthal fibre formation is suggested. We propose that the term Rosenthal fibre be restricted to mean the hyaline amorphous core of these structures, while realizing that this is based on a wider abnormality of surrounding glial fibrillary acidic protein filaments.
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PMID:Rosenthal fibres are based on the ubiquitination of glial filaments. 254 26

Cleavage of the two carboxyl-terminal glycine residues from native ubiquitin yields the proteolysis-incompetent derivative des-Gly-Gly-ubiquitin. We report here that this derivative inhibits the ATP-dependent degradation of casein and is multi-ubiquitinated but not degraded by reticulocyte lysates. Inhibition of proteolysis diminished with increasing concentration of native ubiquitin, but was not reduced by increased casein concentration. Cleavage of the last four residues from ubiquitin yielded a derivative that was a weaker inhibitor of proteolysis and a poorer substrate for ubiquitination. These results suggest that the conjugation of ubiquitin to ubiquitin during polyubiquitin synthesis involves a specific conjugation system that recognizes ubiquitin and some of its derivatives, but not general proteolysis substrates, as ubiquitin acceptors.
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PMID:Inhibition of ubiquitin-dependent proteolysis by des-Gly-Gly-ubiquitin: implications for the mechanism of polyubiquitin synthesis. 254 56

Immunocytochemical studies using antibodies to cytoskeletal proteins have provided conflicting data on the components of paired helical filaments (PHF), due solely to immunological cross-reactivities. To avoid such ambiguity, we developed a protein chemical approach to the identification of the PHF components. After treatment with formic acid, PHF were digested with lysylendopeptidase and the resultant peptides were separated by HPLC. All major peaks were analysed for their amino acid compositions and sequences. From the PHF digest, proteolytic fragments of ubiquitin, tau and beta protein were sequenced. Ubiquitin in PHF appears to be in a conjugated form, while its target protein remains unidentified. Tau is integrated into PHF at the site of its carboxyl third. The presence of beta protein fragments is best interpreted as being due to contamination of amyloid filaments in the PHF preparation. Thus, ubiquitin and tau are the two definite components of PHF.
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PMID:Polypeptide composition of paired helical filaments. 254 40

We have cloned and sequenced a polyubiquitin gene from Neurospora crassa that is organized in a four repeat-tandem array. The first repeat contains a small intron and the last is fused to an extra glutamine codon. In Northern blots, two RNA species of 1.3 kb and 0.7 kb hybridize to the isolated clone. The larger ubiquitin (UBI) transcript accumulates after partial inhibition of protein synthesis with cycloheximide, and the smaller one preferentially accumulates in conidia after germination. Unexpectedly, constitutive expression of UBI transcripts in exponentially grown mycelia is not altered by heat-shock or exposure to arsenite.
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PMID:Ubiquitin expression in Neurospora crassa: cloning and sequencing of a polyubiquitin gene. 254 9


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