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)

We have found an influence of cellular ubiquitin levels over the secretion of human leucocyte elastase inhibitor (elafin) by Saccharomyces cerevisiae. Inactivation of the UBI4 polyubiquitin gene reduced elafin secretion 3 to 4-fold. Conversely ubiquitin overexpression, by galactose induction of an integrated UBI4 gene under GAL1 promoter control, enhanced elafin secretion 7-fold compared to cells wild-type for ubiquitin genes. This influence of ubiquitin levels is exerted at a post-transcriptional step in elafin gene expression, and may represent a chaperone-like action. Ubiquitin overexpression did not affect production of alpha-factor and of certain natural yeast extracellular enzymes even though appreciable free ubiquitin became associated with the yeast periplasm.
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PMID:Overexpression of the gene for polyubiquitin in yeast confers increased secretion of a human leucocyte protease inhibitor. 776 22

Marine sponges, e.g. Geodia cydonium, have been intensively used to investigate the biochemical and molecular biological basis of cell-cell- and cell-matrix adhesion. It has been shown that a family of galactose-specific lectins, which are present in the extracellular space of G. cydonium, is a main component involved in cell-matrix adhesion in the sponge system. In the present study it is outlined that the purified 16-kDa lectin-1 binds to a 67-kDa membrane-associated protein. This lectin-binding protein undergoes mono- and diubiquitination after incubation of dissociated sponge cells with the homologous aggregation factor (AF), a molecule involved in cell-cell adhesion. The gene coding for polyubiquitin was characterized and found to be composed of three tandem repeat building blocks. Northern analysis indicated the presence of only one type of ubiquitin-specific mRNA (1.65 kb). The level of this transcript increased by 10-fold after incubation of the dissociated cells with AF for 8 h; in contrast, lectin-1 caused only a small effect on the steady-state level of ubiquitin mRNA. These data indicate that the expression of the polyubiquitin gene is directly or indirectly regulated by the AF and suggest that ubiquitination might be a process which controls the function of the membrane-associated lectin-binding protein during matrix-cell adhesion.
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PMID:Ubiquitin and ubiquitination in cells from the marine sponge Geodia cydonium. 800 57

In Saccharomyces cerevisiae, the addition of glucose to cells growing on galactose induces internalization of the galactose transporter Gal2p and its subsequent proteolysis in the vacuole. Here we report that the essential step in Gal2p down-regulation is its ubiquitination through the Ubc1p-Ubc4p-Ubc5p triad of ubiquitin-conjugating enzymes and Npi1/Rsp5p ubiquitin-protein ligase. Moreover, Gal2p appears to be stabilized in mutant cells defective in the ubiquitin-hydrolase Npi2p/Doa4p, and the mutant phenotype can be reversed by overexpression of ubiquitin. An analysis of the fate of Gal2p in cells overexpressing wild-type ubiquitin as well as its variants incompetent to form polyubiquitin chains showed that monoubiquitination of Gal2p is sufficient to signal internalization of the protein into the endocytic pathway.
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PMID:Glucose-induced monoubiquitination of the Saccharomyces cerevisiae galactose transporter is sufficient to signal its internalization. 1132 36

Of the many post-translational modifications of proteins, ubiquitination and N-glycosylation stand out because they are polymeric additions. In contrast to single-unit modifications, the fate of the modified protein is determined by the dynamic equilibrium of polymerization versus depolymerization, rather than by the initial addition itself. Notably, it is the trimming of sugar chains and elongation of polyubiquitin that target the protein to degradation. Recent research suggests that, for each process, special receptors recognize chains that reach an appropriate length and commit the conjugated substrate for proteasomal disposal. We propose that the 'magic numbers' are loss of at least three mannose residues from the initial chain, or extension to at least four ubiquitins. Although these processes are compartmentalized to either side of the endoplasmic reticulum (ER) membrane, some proteins are sequentially subjected to both because they transverse this membrane for ER-associated degradation.
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PMID:A window of opportunity: timing protein degradation by trimming of sugars and ubiquitins. 1595 Aug 73

Ascorbate, or vitamin C, is obtained by humans mostly from plant sources. Various approaches have been made to increase ascorbate in plants by transgenic means. Most of these attempts have involved leaf material from model plants, with little success reported using genes from the generally accepted l-galactose pathway of ascorbate biosynthesis. We focused on increasing ascorbate in commercially significant edible plant organs using a gene, GDP-l-galactose phosphorylase (GGP or VTC2), that we had previously shown to increase ascorbate concentration in tobacco and Arabidopsis thaliana. The coding sequence of Actinidia chinensis GGP, under the control of the 35S promoter, was expressed in tomato and strawberry. Potato was transformed with potato or Arabidopsis GGP genes under the control of the 35S promoter or a polyubiquitin promoter (potato only). Five lines of tomato, up to nine lines of potato, and eight lines of strawberry were regenerated for each construct. Three lines of tomato had a threefold to sixfold increase in fruit ascorbate, and all lines of strawberry showed a twofold increase. All but one line of each potato construct also showed an increase in tuber ascorbate of up to threefold. Interestingly, in tomato fruit, increased ascorbate was associated with loss of seed and the jelly of locular tissue surrounding the seed which was not seen in strawberry. In both strawberry and tomato, an increase in polyphenolic content was associated with increased ascorbate. These results show that GGP can be used to raise significantly ascorbate concentration in commercially significant edible crops.
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PMID:Enhancing ascorbate in fruits and tubers through over-expression of the L-galactose pathway gene GDP-L-galactose phosphorylase. 2212 55

Studies into the cell death program termed apoptosis have resulted in new information regarding how cells control and execute their own demise, including insights into the mechanism by which death-preventing factors can inhibit Bax-induced caspase activation. We investigated high temperature stress-induced cell death in Brassica rapa. Using a yeast functional screening from a Brassica rapa cDNA library, the BH5-127 EST clone encoding an apoptotic suppressor peptide was identified. However, a phylogenic tree showed that BH5-127 clusters within a clade containing SUMO-1 (Small Ubiquitin-like Modifier- 1). BH5-127 was confirmed similar to have function to SUMO-1 as Fas suppression. Expression of BH5-127 showed that substantial suppression of cell death survived on SD-galactose-Leu--Ura- medium. The results suggest that BrSE (Brassica rapa Sentrin EST, BH5-127) is one of the important regulatory proteins in programming cell death, especially in the seedling stage of Chinese cabbage.
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PMID:Identification of Chinese cabbage sentrin as a suppressor of Bax-induced cell death in yeast. 2256 52