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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In eukaryotes, the posttranslational conjugation of ubiquitin to various cellular proteins marks them for degradation. Interestingly, several proteins have been reported to contain ubiquitin-like (ub-like) domains that are in fact specified by the DNA coding sequences of the proteins. The biological role of the ub-like domain in these proteins is not known; however, it has been proposed that this domain functions as a degradation signal rendering the proteins unstable. Here, we report that the product of the Saccharomyces cerevisiae RAD23 gene, which is involved in excision repair of UV-damaged DNA, bears a ub-like domain at its amino terminus. This finding has presented an opportunity to define the functional significance of this domain. We show that deletion of the ub-like domain impairs the DNA repair function of RAD23 and that this domain can be functionally substituted by the authentic ubiquitin sequence. Surprisingly, RAD23 is highly stable, and the studies reported herein indicate that its ub-like domain does not mediate protein degradation. Thus, in RAD23 at least, the ub-like domain affects protein function in a nonproteolytic manner.
Mol Cell Biol 1993 Dec
PMID:The Saccharomyces cerevisiae DNA repair gene RAD23 encodes a nuclear protein containing a ubiquitin-like domain required for biological function. 824 91

All eukaryotic cells contain enzymes that are able to catalyze the transfer of Arg from tRNA to the N-terminus of naturally short lived or damaged cytosolic proteins. For certain test proteins, it has been shown that the addition of Arg to the N-terminus leads to their degradation via the ubiquitin proteolytic pathway. The mechanisms used by cells for identifying proteins for arginylation and regulating arginylation are not known. The present study reports the isolation of a peptide from rat brain that is able to inhibit the arginylation of proteins in brain extracts. We suggest that this peptide is the physiological regulator of arginylation in rat brain.
J Mol Neurosci 1993
PMID:Isolation of a peptide that inhibits the posttranslational arginylation of proteins in rat brain. 829 92

The pathology of the Alzheimer's disease (AD) brain, including amyloid plaques, neurofibrillary tangles and neuronal degeneration, indicates that neurons affected by AD exist under conditions of stress. In fact, the brains of AD patients undergo many changes classically associated with the heat shock response, which is one form of a stress response. These changes include reduced protein synthesis, disrupted cytoskeleton, increased number of proteins associated with ubiquitin, and the induction of heat shock proteins. To investigate the response of neurons to stress, we examined neuronal PC12 cells incubated at either 37 degrees C (control cells) or 45 degrees C (heat-shocked cells). After a 30 min exposure at 45 degrees C, the heat-shocked cells exhibited several features characteristic of the classical heat shock response including a 45% reduction in total protein synthesis, the induction of heat shock protein 72, and an increased phosphorylation of the protein synthesis initiation factor eIF-2 alpha. We used this cellular model system to study the neuronal response to stress specifically focusing on protein synthesis elongation factor 2 (EF-2) and the Alzheimer's amyloid precursor protein (APP), the precursor form of beta-amyloid peptide. Hyperphosphorylation of EF-2 has been observed in the neocortex and hippocampus of AD brain. However, in our system, we find no hyperphosphorylation of EF-2 in response to heat shock. Heat-shocked neuronal PC12 cells exhibited two additional APP-like polypeptides not present in controls. We also found a significant decrease in the phosphorylation state of APP in response to heat shock.(ABSTRACT TRUNCATED AT 250 WORDS)
Brain Res Mol Brain Res 1993 Jul
PMID:Altered expression and phosphorylation of amyloid precursor protein in heat shocked neuronal PC12 cells. 836 37

We report genomic linkage of a pair of tandem, identical ubiquitin-extension protein 52 (EP52) genes, a novel EF-hand superfamily member gene (EFH5), and the calmodulin gene cluster in Trypanosoma brucei. The intergenic regions of these four genes are short: about 108 bp between the calmodulin gene C and the EFH5 gene, about 111 bp between the EFH5 gene and the ubiquitin-EP52/1 gene, and about 116 bp between the ubiquitin-EP52/1 and -EP52/2 genes. RNA molecules that span these three intergenic regions have been detected by polymerase chain reaction, which suggests that the genes are transcribed in a polycistronic manner. Transcription of the calmodulin, EFH5, and ubiquitin-EP52 genes in isolated nuclei is rapidly inactivated by UV irradiation, which further strengthens the hypothesis that this cluster of three different genes is transcribed in a polycistronic manner and suggests that they are under the control of a single distant upstream promoter. These results suggest that polycistronic transcription is common in trypanosomes and will probably be found for most, if not all, protein-encoding genes. The presence of at least three housekeeping genes with different known or potential regulatory functions within a polycistronic unit suggests that regulation of transcription initiation plays an important role in the coordinated expression of housekeeping genes in trypanosomes.
Mol Cell Biol 1993 Jan
PMID:Genomic and transcriptional linkage of the genes for calmodulin, EF-hand 5 protein, and ubiquitin extension protein 52 in Trypanosoma brucei. 838 Feb 21

Clathrin-mediated vesicular transport is important for normal growth of the yeast Saccharomyces cerevisiae. Previously, we identified a genetic locus (SCD1) that influences the ability of clathrin heavy-chain-deficient (Chc-) yeast cells to survive. With the scd1-v allele, Chc- yeast cells are viable but grow poorly; with the scd1-i allele, Chc- cells are inviable. To identify the SCD1 locus and other genes that can rescue chc1 delta scd1-i cells to viability, a multicopy suppressor selection strategy was developed. A strain of scd1-i genotype carrying the clathrin heavy-chain gene under GAL1 control (GAL1:CHC1) was transformed with a YEp24 yeast genomic library, and colonies that could grow on glucose were selected. Plasmids from six distinct genetic loci, none of which encoded CHC1, were recovered. One of the suppressor loci was shown to be UBI4, the polyubiquitin gene. UBI4 rescues only in high copy number and is not allelic to SCD1. The conjugation of ubiquitin to intracellular proteins can mediate their selective degradation. Since UBI4 is required for survival of yeast cells under stress and is induced during starvation, ubiquitin expression in GAL1:CHC1 cells was examined. After a shift to growth on glucose to repress synthesis of clathrin heavy chains, UBI4 mRNA levels were elevated > 10-fold, whereas the quantity of free ubiquitin declined severalfold relative to that of Chc+ cells. In addition, novel higher-molecular-weight ubiquitin conjugates appeared in clathrin-deficient cells. We suggest that higher levels of ubiquitin are required for turnover of mislocalized or improperly processed proteins that accumulate in the absence of clathrin and that ubiquitin may play a general role in turnover of proteins in the secretory or endocytic pathway.
Mol Cell Biol 1993 Jan
PMID:Suppressors of clathrin deficiency: overexpression of ubiquitin rescues lethal strains of clathrin-deficient Saccharomyces cerevisiae. 838 Feb 27

The E6 oncoproteins of the cancer-associated or high-risk human papillomaviruses (HPVs) target the cellular p53 protein. The association of E6 with p53 leads to the specific ubiquitination and degradation of p53 in vitro, suggesting a model by which E6 deregulates cell growth control by the elimination of the p53 tumor suppressor protein. Complex formation between E6 and p53 requires an additional cellular factor, designated E6-AP (E6-associated protein), which has a native and subunit molecular mass of approximately 100 kDa. Here we report the purification of E6-AP and the cloning of its corresponding cDNA, which contains a novel open reading frame encoding 865 amino acids. E6-AP, translated in vitro, has the following properties: (i) it associates with wild-type p53 in the presence of the HPV16 E6 protein and simultaneously stimulates the association of E6 with p53, (ii) it associates with the high-risk HPV16 and HPV18 E6 proteins in the absence of p53, and (iii) it induces the E6- and ubiquitin-dependent degradation of p53 in vitro.
Mol Cell Biol 1993 Feb
PMID:Cloning and expression of the cDNA for E6-AP, a protein that mediates the interaction of the human papillomavirus E6 oncoprotein with p53. 838 Aug 95

We describe here the identification of the calmodulin-ubiquitin associated (CUB) genes of Trypanosoma cruzi. A single CUB gene resides in a 1.5-kb DNA sequence linking the calmodulin and ubiquitin genes in the 2.65 and 2.8 loci (CUB2.65 and CUB2.8 respectively). The CUB genes also share the same coding strand as the flanking calmodulin and ubiquitin genes. DNA sequence analysis reveals that each CUB gene contains an open reading frame which would encode a protein of 208 amino acids. The CUB protein shares homology with the recently identified calcium binding EFH5 protein of T. brucei. Transcription of the CUB genes results in the generation of a mRNA of approximately 1.0 kb. CUB cDNA sequence analysis following PCR amplification of the CUB mRNA population indicates that both genes are expressed and trans-spliced, but utilize different 3' acceptor sites for the trans-splicing reaction.
Mol Biochem Parasitol 1993 Jan
PMID:The calmodulin-ubiquitin associated genes of Trypanosoma cruzi: their identification and transcription. 838 Dec 4

Analysis of gene expression in Trypanosoma cruzi has been impeded by the lack of efficient, stable, DNA-mediated transfection systems. We describe here the establishment of such a system for T. cruzi. Stable transformants were isolated following integration of the circular transforming plasmid into the chromosome by homologous recombination. Mutants with a disrupted PUB12.5 polyubiquitin gene, resulting from targeted integration of the plasmid vector, have been isolated. A mutant harboring the disrupted PUB12.5 gene lacks the intact PUB12.5 mRNA as well as transcripts corresponding to the truncated gene. Genomic Southern-blot analysis indicates that the inserted plasmid is tandemly repeated in each of the clones analyzed. A secondary recombination event in one clone resulted in a deletion within the 2.65 calmodulin-ubiquitin locus, encompassing the sequence from the CalA2 calmodulin gene to the PUB12.5 polyubiquitin gene.
Mol Biochem Parasitol 1993 Jan
PMID:Stable transformation of Trypanosoma cruzi: inactivation of the PUB12.5 polyubiquitin gene by targeted gene disruption. 838 Dec 5

Despite considerable effort there is no consensus as to what interaction, or set of interactions, provides the dominant force that drives protein folding and specifies folded protein structures. A key thermodynamic observation is that a large drop in heat capacity (delta Cp) usually accompanies folding in water. Various factors may contribute to this effect, especially changes in the structure of the solvent upon exposure of both non-polar and polar groups in the unfolded state. The unfavourable Gibbs free energy of solvating non-polar groups, in particular, is thought to provide a central driving force for folding (the hydrophobic effect) but the role of solvent ordering in this remains a matter of controversy. We report here a series of experiments that show that a protein can fold into its native conformation under conditions where solvent ordering effects are demonstrably negligible. In methanol/water mixtures ubiquitin unfolds reversibly with a delta Cp value that falls close to zero above about 30% (v/v) methanol. We are able to reason, on the basis of these data, that the net contribution to the heat capacity change arising primarily from the protein structure itself is not significant and that contributions from changes in solvent ordering are rendered negligible by the change in composition. Nuclear magnetic resonance measurements, however, indicate that non-polar side-chains do still become exposed to solvent in the denatured state under these conditions. The combination of these results and model compound studies suggests that the elimination of ordering effects is an intrinsic property of the mixed solvent. We can, therefore, conclude that the solvent ordering component of the hydrophobic effect is not an obligatory factor in determining the three-dimensional structure into which the protein will fold.
J Mol Biol 1993 Jan 20
PMID:Protein folding in the absence of the solvent ordering contribution to the hydrophobic interaction. 838 93

Ubiquitin is an omnipresent protein found in all eukaryotes so far analysed. It is involved in several important processes, including protein turnover, chromosome structure and stress response. Parsley (Petroselinum crispum) contains at least two active polyubiquitin (ubi4) genes encoding hexameric precursor proteins. The deduced amino acid sequences of the ubiquitin monomers are identical to one another and to ubiquitin sequences from several other plant species. Analysis of the promoter region of one ubi4 gene revealed putative regulatory elements. In parsley plants, the ubi4 mRNAs were the predominant ubiquitin mRNAs and were present at comparable levels in all plant organs tested. In cultured parsley cells, high levels of ubiquitin gene expression remained unaffected by heat shock, elicitor or light treatment.
Plant Mol Biol 1993 Feb
PMID:Polyubiquitin gene expression and structural properties of the ubi4-2 gene in Petroselinum crispum. 838 52


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