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)

A cDNA of the sea urchin Strongylocentrotus purpuratus was identified as encoding polyubiquitin and used to detect a single gene with transcripts containing multiple ubiquitin coding units. Polyubiquitin transcripts exist as a 3.2-kb RNA in polyribosomes and as three higher molecular weight RNAs in purified nuclei. The amount of polyubiquitin RNA is essentially constant at 10(4) -10(5) transcripts per embryo during the egg-to-blastula period and then declines during further development. Heat shock elicits a transient increase in the level of polyubiquitin RNA, while Zn(II) ions induce a sustained accumulation, that is influenced by developmental parameters: One round of Zn(II) induction elicits the accumulation of the nuclear 7.6- and 5.6-kb RNAs, as well as the 3.2-kb polysomal RNA; however, a second round of induction yields only the 5.6- and 3.2-kb RNAs, suggestive of a change in pre-mRNA size or processing. Polyubiquitin RNA is expressed equally in ectodermal and mesoendodermal tissues and is induced in both tissue fractions by treatment of pluteus larvae with Zn(II). However, in isolated and cultured tissue fractions, polyubiquitin RNA is not inducible by Zn(II), in contrast to the full inducibility of metallothionein mRNAs. Polyubiquitin RNA induction thus appears to be conditioned by the integrity of the embryo, as well as by previous exposure to inducer.
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PMID:Polyubiquitin RNA characteristics and conditional induction in sea urchin embryos. 164 80

Antibodies to ubiquitin have been used to search for evidence of abnormal protein degradation in amyotrophic lateral sclerosis--motor neuron disease (ALS). Anterior horn cell ubiquitin-immunoreactive (IR) inclusions were present in all of 31 ALS cases but in none of 23 neurologically normal and in only 1 of 22 neurologically abnormal controls. These inclusions, which were present in familial and sporadic ALS cases, and in cases with dementia, took the form of dense rounded or irregular ubiquitin-IR cytoplasmic inclusions (dense bodies), or loosely arranged bundles ('skeins') of filamentous-appearing material. The presence of ubiquitin-IR inclusions corresponded to the pattern of selective neuronal vulnerability in ALS, although inclusions in pyramidal neurons of the motor cortex were infrequent and were noted in only a minority of cases. Ubiquitin-IR inclusions were more prevalent than Bunina bodies. The latter were present in 67% of ALS cases but were seldom labelled by antibodies to ubiquitin. Intraneuronal inclusions resembling Lewy bodies were present in 23% of ALS cases and were often identified by antibodies to ubiquitin. We conclude that the presence of ubiquitin-IR inclusions in lower motor neurons represents a characteristic pathological feature of ALS in its various clinical forms. Ubiquitin-IR inclusions in ALS differ from ubiquitinated inclusions in other neuronal degenerations in that they are not readily identified by antibodies to cytoskeletal proteins. They may represent accumulations of altered or abnormal neuronal proteins resistant to degradation via the ubiquitin proteolytic pathway.
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PMID:Ubiquitin-immunoreactive intraneuronal inclusions in amyotrophic lateral sclerosis. Morphology, distribution, and specificity. 164 64

Studies in recent years have shown that ubiquitin has increasingly important functions in eukaryotic cells; roles which were previously not suspected in healthy and diseased cells. The interplay between molecular pathological and molecular cell biological findings has indicated that ubiquitin may be pivotal in the cell stress response in chronic degenerative and viral diseases. Furthermore, the studies have led to the notion that ubiquitination may not only serve as a signal for nonlysosomal protein degradation but may be a unifying covalent protein modification for the major intracellular protein catabolic systems; these can act to identify proteins for cytosolic proteinases or direct intact and fragmented proteins into the lysosome system for breakdown to amino acids. This unifying role could explain why ubiquitin is restricted to eukaryotic cells, which possess extensive endomembrane systems in addition to a nuclear envelope. Protein ubiquitination is a feature of most filamentous inclusions and certain other intracellular conglomerates that are found in some degenerative and viral diseases. The detection of ubiquitin-protein conjugates is not of great diagnostic importance in these diseases. Protein ubiquitination is not only essential for the normal physiological turnover of proteins but appears to have been adapted as part of an intracellular surveillance system that can be activated by altered, damaged, or foreign proteins and organelles. The purpose of this system is to isolate and eliminate these noxious structures from the cell: as a cytoprotective mechanism this appears to have evolved in the cell akin perhaps to an 'intracellular immune system'. Other heat shock proteins such as hsp 70 may be involved in this process. It is apparent that ubiquitin has a role in embryonic development. Protein ubiquitination is presumably involved in the reorganisation of cytoplasm that accompanies cell differentiation. Ubiquitin is also necessary for the gross intracellular degradative processes which are consequent upon programmed cell death. Cell elimination is of key importance for a number of developmental morphogenetic changes. An understanding of the molecular details of these processes will no doubt provide further insights into the wide ranging roles of ubiquitin in the life process. As it says in the book 'Ubiquitin'; there is no doubt that ubiquitin is a 'lucky' protein. It is lucky in many ways: lucky for scientific progress, lucky for biomedical scientists and lucky for life! If you have not already done so, why don't you get lucky and look for a role for ubiquitin in your experimental system. As Avram Hershko has said "there is plenty to go round"!
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PMID:Ubiquitin in health and disease. 164 8

Several neurodegenerative diseases, including motor neuron disease (MND), are characterized by formation of abnormal cytoskeleton-derived inclusions which contain ubiquitin (Ubq). We have studied the distribution of Ubq in 26 cases of MND with light and electron microscopic immunocytochemistry. Ubiquitin-positive inclusions were found in neurons of anterior horns in most cases of amyotrophic lateral sclerosis (ALS) but were not present in other forms of MND. Ubiquitin immunoreactivity was observed in 10-15 nm intraneuronal filaments, which were not stained by antibodies to neurofilaments, and on dense bodies of dystrophic neurites throughout the neuropil of anterior horns and pyramidal tracts. Data analysis showed a trend toward lower percentage of Ubq-positive neurons in cases with longer duration of illness or lower number of neurons. A high percentage of Ubq-positive inclusions occurred in cases with an aggressive clinical course, suggesting that ubiquitination takes place at early stages of the disease.
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PMID:Ubiquitin in motor neuron disease: study at the light and electron microscope. 164 24

Ubiquitin-protein conjugates and alpha B crystallin are detected immunohistochemically in cells undergoing extensive morphological reorganisation in early chicken embryos. Cytoplasmic ubiquitinated proteins and alpha B crystallin are coordinately found in cells of the lens, notochord and myotome. The antigens appear in the myotome cells precisely at the point at which the cells begin to migrate from the dorsomedial lip of the dermamyotome. The findings indicate that ubiquitin and alpha B crystallin may have a coordinate role in the extensive architectural remodeling which occurs in these developing tissues in the early chick embryo. Some form of functional association between protein ubiquitination and alpha B crystallin in cells may explain why alpha B crystallin is found with ubiquitin-protein deposits in some neurodegenerative diseases.
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PMID:Ubiquitin-protein conjugates and alpha B crystallin are selectively present in cells undergoing major cytomorphological reorganisation in early chicken embryos. 164 16

Pathways of ubiquitin-dependent protein degradation have in common two requirements for ATP. Ubiquitin activation by the enzyme E1 is accompanied by ATP hydrolysis to yield AMP and PPi, and during conjugate breakdown, the ubiquitin-dependent protease hydrolyzes ATP to ADP and Pi. We show here that either of two beta, gamma-nonhydrolyzable ATP analogues, 5'-adenylyl imidodiphosphate or 5'-adenylyl methylenediphosphate, can support ubiquitin-protein conjugation. With the ubiquitin-dependent protease, however, neither analogue could substitute for ATP. Thus, the substitution of a beta, gamma-nonhydrolyzable analogue for ATP offers a simple method to uncouple ubiquitin conjugation from proteolysis in crude systems. On the basis of pyrophosphate exchange kinetics, E1 has apparent Km and Vmax values that are similar for ATP and the analogues, but substrate inhibition by 5'-adenylyl methylenediphosphate made use of the beta, gamma-imido analogue preferable. In one application, beta, gamma-imido-ATP was used in combination with ubiquitin aldehyde (an inhibitor of ubiquitin-protein isopeptidases) to establish that several unfolded RNase A derivatives are recognized equally as ubiquitination substrates. This result extends an earlier study [Dunten, R. L., & Cohen, R. E. (1989) J. Biol. Chem. 264, 16739-16747] to show that conjugate yields, upon which relative ubiquitination rates were based, were not influenced by differential ubiquitin-dependent proteolysis. In a second application, ATP and beta, gamma-imido-ATP were compared in a pulse-chase experiment to investigate the contributions of ATP-dependent proteolysis and isopeptidase activities to conjugate stability.
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PMID:Uncoupling ubiquitin-protein conjugation from ubiquitin-dependent proteolysis by use of beta, gamma-nonhydrolyzable ATP analogues. 164 32

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.
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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.
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PMID:Methylated ubiquitin inhibits cyclin degradation in clam embryo extracts. 165 32

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

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.
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PMID:Ubiquitin-immunoreactive dystrophic neurites in Down's syndrome brains. 165 99


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