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Query: UNIPROT:P62988 (Ubiquitin)
 4,326 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ubiquitin is a highly conserved, multifunctional protein, which is implicated in the heat-shock response of eukaryotes. The differential expression of the multiple ubiquitin genes in Dictyostelium discoideum was investigated under various stress conditions. Growing D. discoideum cells express four major ubiquitin transcripts of sizes varying from 0.6 to 1.9 kb. Upon heat shock three additional ubiquitin mRNAs of 0.9, 1.2 and 1.4 kb accumulate within 30 min. The same three transcripts are expressed in response to cold shock or cadmium treatment. Inhibition of protein synthesis by cycloheximide leads to a particularly strong accumulation of the larger ubiquitin transcripts, which code for polyubiquitins. Possible mechanisms regulating the expression of ubiquitin transcripts upon heat shock and other stresses are discussed.
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PMID:Ubiquitin gene expression in Dictyostelium is induced by heat and cold shock, cadmium, and inhibitors of protein synthesis. 284 53

Using homologous molecular probes, we examined the influence of equivalent temperature shifts on the in vivo expression of genes coding for a constitutive heat shock protein (Hsc70), heat shock proteins (Hsps) (Hsp70 and Hsp90), and polyubiquitin, after acclimation in the American lobster, Homarus americanus. We acclimated sibling, intermolt, juvenile male lobsters to thermal regimes experienced during overwintering conditions (0.4 +/- 0.3 degrees C), and to ambient Pacific Ocean temperatures (13.6 +/- 1.2 degrees C), for 4-5 weeks. Both groups were subjected to an acute thermal stress of 13.0 degrees C, a temperature shift previously found to elicit a robust heat shock response in ambient-acclimated lobsters. Animals were examined after several durations of acute heat shock (0.25-2 hours) and after several recovery periods (2-48 hours) at the previous acclimation temperature, following a 2-hour heat shock. Significant inductions in Hsp70, Hsp90, and polyubiquitin messenger RNA (mRNA) levels were found for the ambient-acclimated group. Alternatively, for the cold-acclimated group, an acute thermal stress over an equivalent interval resulted in no induction in mRNA levels for any of the genes examined. For the ambient-acclimated group, measurements of polyubiquitin mRNA levels showed that hepatopancreas, a digestive tissue, incurred greater irreversible protein damage relative to the abdominal muscle, a tissue possessing superior stability over the thermal intervals tested.
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PMID:Thermal acclimation and stress in the American lobster, Homarus americanus: equivalent temperature shifts elicit unique gene expression patterns for molecular chaperones and polyubiquitin. 1189 92

The 26S proteasome involved in degradation of proteins covalently modified with polyubiquitin consists of the 20S proteasome and 19S regulatory complex. The NbPAF gene encoding the alpha6 subunit of the 20S proteasome was identified from Nicotiana benthamiana. NbPAF exhibits high sequence homology with the corresponding genes from Arabidopsis, human and yeast. The deduced amino acid sequence of NbPAF reveals that this protein contains the proteasome alpha-type subunits signature and nuclear localization signal at the N-terminus. The genomic Southern blot analysis suggests that the N. benthamiana genome contains one copy of NbPAF. The NbPAF mRNA was detected abundantly in flowers and weakly in roots and stems, but it was almost undetectable in mature leaves. In response to stresses, accumulation of the NbPAF mRNA was stimulated by methyl jasmonate, NaCl and salicylic acid, but not by abscisic acid and cold treatment in leaves. The NbPAF-GFP fusion protein was localized in the cytoplasm and nucleus.
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PMID:Molecular characterization of NbPAF encoding the alpha6 subunit of the 20S proteasome in Nicotiana benthamiana. 1266 72

Water-soluble proteins encapsulated within reverse micelles may be studied under a variety of conditions, including low temperature and a wide range of buffer conditions. Direct high-resolution detection of information relating to protein folding intermediates and pathways can be monitored by low-temperature solution NMR. Ubiquitin encapsulated within AOT reverse micelles was studied using multidimensional multinuclear solution NMR to determine the relationship between protein structure, temperature, and ionic strength. Ubiquitin resonances were monitored by 15N HSQC NMR experiments at varying temperatures and salt concentrations. Our results indicate that the structure of the encapsulated protein at low temperature experiences perturbation arising from two major influences, which are reverse micelle-protein interactions and low-temperature effects (e.g., cold denaturation). These two effects are impossible to distinguish under conditions of low ionic strength. Elevated concentrations of nondenaturing salt solutions defeat the effects of reverse micelle-protein interactions and reveal low-temperature protein unfolding. High ionic strength shielding stabilizes the reverse micelle at low temperatures, which reduces the electrostatic interaction between the protein and reverse micelle surfaces, allowing the phenomenon of cold denaturation to be explored.
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PMID:Low-temperature studies of encapsulated proteins. 1619 Jul 19

Ubiquitin-mediated proteolysis plays a key role in many pathways inside the cell and is particularly important in regulating cell cycle transitions. SCF (Skp1/Cul1/F-box protein) complexes are modular ubiquitin ligases whose specificity is determined by a substrate-binding F-box protein. Dia2 is a Saccharomyces cerevisiae F-box protein previously described to play a role in invasive growth and pheromone response pathways. We find that deletion of DIA2 renders cells cold-sensitive and subject to defects in cell cycle progression, including premature S-phase entry. Consistent with a role in regulating DNA replication, the Dia2 protein binds replication origins. Furthermore, the dia2 mutant accumulates DNA damage in both S and G2/M phases of the cell cycle. These defects are likely a result of the absence of SCF(Dia2) activity, as a Dia2 DeltaF-box mutant shows similar phenotypes. Interestingly, prolonging G1-phase in dia2 cells prevents the accumulation of DNA damage in S-phase. We propose that Dia2 is an origin-binding protein that plays a role in regulating DNA replication.
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PMID:The F-box protein Dia2 regulates DNA replication. 1642 Dec 50

Nuclear Magnetic Resonance (NMR) spectroscopy is a key experimental technique used to study protein structure, dynamics, and interactions. NMR methods face the bottleneck of spectral analysis, in particular determining the resonance assignments, which help define the mapping between atoms in the protein and peaks in the spectra. A substantial amount of noise in spectral data, along with ambiguities in interpretation, make this analysis a daunting task, and there exists no generally accepted measure of uncertainty associated with the resulting solutions. This paper develops a model-based inference approach that addresses the problem of characterizing uncertainty in backbone resonance assignment. We argue that NMR spectra are subject to random variation, and ignoring this stochasticity can lead to false optimism and erroneous conclusions. We propose a Bayesian statistical model that accounts for various sources of uncertainty and provides an automatable framework for inference. While assignment has previously been viewed as a deterministic optimization problem, we demonstrate the importance of considering all solutions consistent with the data, and develop an algorithm to search this space within our statistical framework. Our approach is able to characterize the uncertainty associated with backbone resonance assignment in several ways: 1) it quantifies of uncertainty in the individually assigned resonances in terms of their posterior standard deviations; 2) it assesses the information content in the data with a posterior distribution of plausible assignments; and 3) it provides a measure of the overall plausibility of assignments. We demonstrate the value of our approach in a study of experimental data from two proteins, Human Ubiquitin and Cold-shock protein A from E. coli. In addition, we provide simulations showing the impact of experimental conditions on uncertainty in the assignments.
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PMID:Model-based assignment and inference of protein backbone Nuclear Magnetic Resonances. 1664 22

Rodent hibernators experience low core body temperature (as low as -2 degrees C) and reduced metabolic rates during hibernation. Concordant with energetic constraints, protein synthesis is negligible during torpor. To maintain pools of key regulatory proteins, proteolysis must be depressed as well. Ubiquitin-dependent proteolysis consists of two major steps: (1) ubiquitylation or tagging of a protein substrate by ubiquitin and (2) the protein substrate's subsequent degradation by the 26S proteasome. Earlier, we demonstrated that the low temperatures typical of torpor virtually arrest proteolytic processing. Here, we demonstrate that in vitro ubiquitylation still continues at greater than 30% of maximal rates at temperatures as low as 0 degrees C. Continued ubiquitylation in the presence of severely depressed proteolysis may explain the previously observed 2- to 3-fold increase of ubiquitin conjugates during torpor. We determined if there is a qualitative change in the type of ubiquitylation e.g., monoubiquitylation vs polyubiquitylation that occurs during torpor. We found no bias for monoubiquitylation in any state of the torpor cycle. We further determined that substrate limitation of free ubiquitin is not limiting ubiquitylation during torpor. We conclude that while the cold temperatures of torpor may limit proteolysis in accordance with metabolic demands, continued ubiquitylation may result in increased ubiquitin conjugate concentrations that must be processed upon arousal.
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PMID:Ubiquitylation of proteins in livers of hibernating golden-mantled ground squirrels, Spermophilus lateralis. 1789 39

In a morning in January, a male in his early sixties was found dead in an outdoor parking area. The minimum temperature during the night before he was found dead was estimated to be 4.0 degrees C. Autopsy revealed the pinkness of hypostasis, slight abrasions and bruises on the face and the extremities, collapse of the lungs, and slight gastric submucosal hemorrhage. Histologic examination revealed compact arrangement of cardiac muscle fibers and cytoplasmic vacuolation in the adenohypophysis. Toxicologic examination demonstrated hyperacetonemia (51.2 microg/mL). Ubiquitin, one of the stress proteins that are induced by several stimuli, including severe cold, was detected in several organs. We concluded that the cause of his death was lethal hypothermia. In addition, hemorrhages were observed in the subfascial and/or intramuscular parts of the pectoralis minor, first intercostal, and iliopsoas muscles. Although it has been reported that iliopsoas muscle hemorrhage can result from hypothermia, there have been few reports concerning hypothermia-associated hemorrhages of the pectoralis minor and/or intercostal muscles. We presumed that intense shivering and/or effort ventilation during the course of lethal hypothermia might cause these muscle hemorrhages.
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PMID:A fatal case of hypothermia associated with hemorrhages of the pectoralis minor, intercostal, and iliopsoas muscles. 1804 25

Ubiquitin (Ub) is a highly conserved 8-kDa protein that was first identified as a tag for protein degradation. Recently, its role in nonproteolytic cellular processes such as DNA repair and endocytosis has also been reported. An ubiquitin-fusion gene was cloned from Musca domestica. The complete length of this ubiquitin-fusion gene is 531 bp, of which 471 bp is an open reading frame (ORF) encoding a 156-amino acid peptide, and 60 bp is a 3'-untranslated region with the polyadenylation sequence AATAAA and a poly(A) tail. The ubiquitin-fusion protein includes an ubiquitin monomer of 76 amino acids with a 6-amino acid motif (LRLRGG) and 3 conserved lysine functional sites, which participate in the formation of the ubiquitin-protease complex. The ubiquitin-fusion protein also contains an 80-amino acid carboxyl extension protein, namely, ribosomal protein S27 with a classical zinc finger motif C-X(4)-C-X(14)-C-X(2)-C. Because of its carboxyl extension protein S27, the M. domestica ubiquitin-fusion protein was named Mub(S27). It has a predicted molecular weight of 18 kDa and a theoretical isoelectric point of 9.82. No signal peptides were predicted for the protein. Northern blot analysis revealed that Mub(S27) transcript level is higher at the embryo stage than that at any other developmental stages. When houseflies develop into 5-day pupae, the Ub mRNA level is relatively low. After infection with gram-negative and gram-positive bacteria, Mub(S27) transcript level was upregulated. Mub(S27) transcript level was also regulated by heat or cold stress.
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PMID:Gene cloning and expression analysis of ubiquitin derived from Musca domestica. 1848 1

Unlike most ordered molecular systems, globular proteins exhibit a temperature of maximum stability, implying that the structure can be disrupted by cooling. This cold denaturation phenomenon is usually linked to the temperature-dependent hydrophobic driving force for protein folding. Yet, despite the key role played by protein-water interactions, hydration changes during cold denaturation have not been investigated experimentally. Here, we use water-(17)O spin relaxation to monitor the hydration dynamics of the proteins BPTI, ubiquitin, apomyoglobin, and beta-lactoglobulin in aqueous solution from room temperature down to -35 degrees C. To access this temperature range without ice formation, we contained the protein solution in nonperturbing picoliter emulsion droplets. Among the four proteins, only the destabilized apomyoglobin was observed to cold denature. Ubiquitin was found to be thermodynamically stable at least down to -32 degrees C, whereas beta-lactoglobulin is expected to be unstable below -5 degrees C but remains kinetically trapped in the native state. When destabilized by 4 M urea, beta-lactoglobulin cold denatures at 10 degrees C, as found previously by other methods. As seen from the solvent, the cold-denatured states of apomyoglobin in water and beta-lactoglobulin in 4 M urea are relatively compact and are better described as solvent-penetrated than as unfolded. This finding challenges the popular analogy between cold denaturation and the anomalous low-temperature increase in aqueous solubility of nonpolar molecules. Our results also suggest that the reported cold denaturation at -20 degrees C of ubiquitin encapsulated in reverse micelles is caused by the low water content rather than by the low temperature.
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PMID:Protein cold denaturation as seen from the solvent. 1911 52


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