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

The modification of cytosolic proteins with polyubiquitin chains targets them for recognition and degradation by the multisubunit proteolytic particle, the 26S proteasome. Membrane proteins are also substrates for ubiquitination. Integral membrane proteins of the endoplasmic reticulum are ubiquitinated and destroyed by the proteasome. However, it has been shown recently that the ubiquitination of Saccharomyces cerevisiae plasma membrane proteins signals their degradation by the proteolytic system in the lysosome-like vacuole. Ubiquitination of several different classes of cell surface proteins serves as a signal for their entry into the endocytic pathway; this leads to their transport to the vacuole, where they are permanently inactivated by degradation. In yeast, ubiquitin has been implicated as an internalization signal for most, if not all, endogenous plasma membrane proteins that are known to be endocytosed. Ubiquitin-dependent internalization has been best characterized for two proteins: the mating pheromone alpha-factor receptor and the uracil permease. Some mammalian cell surface receptors are also ubiquitinated at the plasma membrane. Ubiquitination machinery is required for ligand-induced endocytosis of the growth hormone receptor, suggesting that ubiquitin-dependent endocytosis and sorting is also an important regulatory process in mammalian cells. Mammalian receptors may also be down-regulated through the degradation of their cytosolic domains by a proteasome-dependent pathway.
FASEB J 1997 Dec
PMID:Ubiquitin-dependent internalization and down-regulation of plasma membrane proteins. 940 40

Ubiquitin ligases are generally assumed to play a major role in substrate recognition and thus provide specificity to a particular ubiquitin modification system. The multicopy maintenance protein (Mcm) 7 subunit of the replication licensing factor-M was identified as a substrate of the E3-ubiquitin ligase/E6-AP by its interaction with human papillomavirus-18E6. Mcm7 is ubiquitinated in vivo in both an E6-AP-dependent and -independent manner. E6-AP functions in these reactions independently of the viral oncogene E6. We show that recognition of Mcm7 by E6-AP is mediated by a homotypic interaction motif present in both proteins, called the L2G box. These findings served as the basis for the definition of substrate specificity for E6-AP. A small cluster of proteins whose function is intimately associated with the control of cell growth and/or proliferation contains the L2G box and is thereby implicated in an E6-AP and, by default, HPV-E6-dependent ubiquitination pathway.
J Biol Chem 1998 Dec 18
PMID:E3-ubiquitin ligase/E6-AP links multicopy maintenance protein 7 to the ubiquitination pathway by a novel motif, the L2G box. 985 95

The NEDD8/Rub1 class of ubiquitin-like proteins has been implicated in progression of the cell cycle from G1 into S phase. These molecules undergo a metabolism that parallels that of ubiquitin and involves specific interactions with many different proteins. We report here the crystal structure of recombinant human NEDD8 refined at 1.6-A resolution to an R factor of 21.9%. As expected from the high sequence similarity (57% identical), the NEDD8 structure closely resembles that reported previously for ubiquitin. We also show that recombinant human NEDD8 protein is activated, albeit inefficiently, by the ubiquitin-activating (E1) enzyme and that NEDD8 can be transferred from E1 to the ubiquitin conjugating enzyme E2-25K. E2-25K adds NEDD8 to a polyubiquitin chain with an efficiency similar to that of ubiquitin. A chimeric tetramer composed of three ubiquitins and one histidine-tagged NEDD8 binds to the 26 S proteasome with an affinity similar to that of tetraubiquitin. Seven residues that differ from the corresponding residues in ubiquitin, but are conserved between NEDD8 orthologs, are candidates for mediating interactions with NEDD8-specific partners. One such residue, Ala-72 (Arg in ubiquitin), is shown to perform a key role in selecting against reaction with the ubiquitin E1 enzyme, thereby acting to prevent the inappropriate diversion of NEDD8 into ubiquitin-specific pathways.
J Biol Chem 1998 Dec 25
PMID:Crystal structure of the human ubiquitin-like protein NEDD8 and interactions with ubiquitin pathway enzymes. 985 30

This study addresses the relationship of epitope-specific Ab responses and alternative autoantibody responses in a model system in which an antigenized self protein serves as the carrier for a defined heterologous B cell epitope. Ubiquitin, a nonimmunogenic self protein, was engineered to present heterologous B and T cell epitopes in the recombinant molecule. Fusion to the C terminus introduced a universal T cell epitope from a Mycobacterium tuberculosis Ag. The B cell epitope was created by inserting a 12-residue loop sequence of HIV-1 gp120 at a surface-exposed position of ubiquitin. These modifications preserved the ubiquitin fold, allowing a new conformational epitope to be presented among native self epitopes. Mice immunized with the hybrid protein bearing only the mycobacterial T cell epitope elicited a strong autoantibody response to native ubiquitin. In contrast, antisera elicited against hybrid ubiquitin presenting the HIV B cell epitope reacted specifically with the foreign epitope but not with native ubiquitin. Absence of autoantibody in the response was attributed to poor competition of autoreactive B cells for limiting T cell help. Both types of responses were associated with Th responses to defined epitopes of the ubiquitin hybrid protein. These results may have implications for a tolerance mechanism dependent on B-T cell cooperation.
J Immunol 1998 Dec 15
PMID:Epitope-specific antibody and suppression of autoantibody responses against a hybrid self protein. 986 76

We have identified 39 Arabidopsis thaliana ESTs encoding germin-like proteins (GLPs) and have completely sequenced 25 of these cDNAs. Our analysis demonstrates that the Arabidopsis genome contains a gene family with at least 12 GLP genes. Comparisons with other known germins and germin-like proteins indicate that these Arabidopsis GLP subfamilies are unique from wheat germin. All other known GLPs fall into one of these subfamilies. The translated GLPs show approximately 35% amino acid identity with other GLPs outside of their subfamily and significantly higher levels of identity within their respective subfamily. The 3' ends of many of the GLP cDNAs are heterogeneous and several sites of polyadenylation are used. Ten of the GLPs have N-terminal signal sequences and most appear to be exported from the cell. Structurally, the GLPs are predicted to have a high content of beta-pleated sheet. Seven conserved regions of beta-sheet were found in each of the GLP proteins along with alpha-helices located at both N- and C-termini. These same structural elements are also conserved in wheat germin. With one exception, all GLP family members contain at least one N-glycosylation site. All of these sites are conserved in an unstructured loop between beta-1 and beta-2. Genes for two of these GLPs were identified in genomic sequences previously deposited in the GenBank. The GLP3b gene is physically linked to the polyubiquitin 4 gene. The 3' end of the GLP3b mRNA is only 0.5 kb from the ubq4 start of transcription. Analysis of the GLP3b promoter shows the presence of a single putative auxin-response sequence located at -124 to -111 upstream from the 5' end of the GLP3b mRNA. The GLP9 gene was identified in an Arabidopsis contig from Chromosome 4.
Plant Mol Biol 1998 Dec
PMID:Arabidopsis thaliana contains a large family of germin-like proteins: characterization of cDNA and genomic sequences encoding 12 unique family members. 986

Gibberella pulicaris, a causal agent of potato dry rot, infects potato tubers via wounds, where it is exposed to the phytoalexins rishitin and lubimin. Incubation of mycelium on agar supplemented with phytoalexins transiently induced the transcription of a polyubiquitin gene consisting of four ubiquitin units arranged head to tail; the fourth unit contains a 54-bp intron and an additional glutamine at the C-terminus of the encoded protein. Southern analysis of the G. pulicaris genome revealed one copy of the isolated polyubiquitin gene and one or two copies of other ubiquitin genes. Increased transcription of the gene was detectable above a threshold of 100 microg/ml of rishitin and at elevated temperatures, which indicates that exposure to phytoalexins causes a stress reaction of hyphal cells similar to that after heat shock.
Curr Genet 1998 Dec
PMID:Induction of a polyubiquitin gene (ubi1) by potato phytoalexins and heat shock in Gibberella pulicaris. 987 Nov 24

We investigated the hippocampal pathology in diffuse Lewy body disease (DLBD) using alpha-synuclein immunohistochemistry. Ubiquitin-positive intrahippocampal structures caused by the degeneration of terminal axons of the perforant pathway were observed to be alpha-synuclein immunoreactive. These alpha-synuclein-positive degenerative terminals contained granulo-filamentous or vesiculo-tubular components similar to those of Lewy bodies (LB) immunoelectron microscopically, suggesting that alpha-synuclein may abnormally aggregate into filamentous or membranous cytoskeletal components including neurofilaments and synaptic vesicles in DLBD. A 'dying back' degenerating process due to a blockage of axonal transport may explain why the degenerative terminals and LB share similar alpha-synuclein-positive components, but the origin cells of the perforant pathway contain only a few LB.
Neurosci Lett 1998 Dec 18
PMID:Degenerative terminals of the perforant pathway are human alpha-synuclein-immunoreactive in the hippocampus of patients with diffuse Lewy body disease. 987 32

Ubiquitin-conjugating enzymes (E2 or Ubc) play a key role in the post-translational modification of proteins by ubiquitylation. They are encoded by a large family of genes that are closely related to each other. In this paper we present the first complete structural analysis, including the promoter and the chromosomal location, of a member of this family, the mouse Ubcm4 gene. At the genomic level the Ubcm4 gene spans approx. 50kb and is composed of four exons. Only about 1% of the total gene codes for amino acids. The four different Ubcm4 specific RNAs encode the same protein and differ only in the length of the 3' untranslated region. The polyadenylation signals used by the four different RNAs are all within the 3' terminal exon. At the 5' end of the gene, multiple transcriptional start sites were mapped within a region of 25bp. The region proximal to the initiation sites does not contain a TATA box and is not GC-rich. Transient chloramphenicol acetyltransferase assays, however, showed that this region can promote the expression of a reporter gene and that 15bp upstream of the first initiation site were sufficient for basal expression. The Ubcm4 gene was mapped by interspecific backcross analysis to the proximal region of mouse chromosome 16.
Gene 1998 Dec 11
PMID:Structure of the gene encoding the ubiquitin-conjugating enzyme Ubcm4, characterization of its promoter, and chromosomal location. 993 61

The ubiquitin-like protein RUB1 is conjugated to target proteins by a mechanism similar to that of ubiquitin conjugation. Genetic studies in Arabidopsis thaliana have implicated the RUB-conjugation pathway in auxin response. The first step in the pathway is RUB activation by a bipartite enzyme composed of the AXR1 and ECR1 proteins. Ubiquitin activation is an ATP-dependent process that involves the formation of an AMP-ubiquitin intermediate. Here we show that RUB activation by AXR1-ECR1 also involves formation of an AMP-RUB intermediate and that this reaction is catalyzed by the ECR1 subunit alone. In addition, we identified an Arabidopsis protein called RCE1 that is a likely RUB-conjugating enzyme. RCE1 works together with AXR1-ECR1 to promote formation of a stable RUB conjugate with the Arabidopsis cullin AtCUL1 in vitro. Using a tagged version of RUB1, we show that this modification occurs in vivo. Because AtCUL1 is a component of the ubiquitin protein ligase SCF(TIR1), a complex that also functions in auxin response, we propose that RUB modification of AtCUL1 is important for auxin response.
Proc Natl Acad Sci U S A 1999 Dec 21
PMID:The Arabidopsis cullin AtCUL1 is modified by the ubiquitin-related protein RUB1. 1061 86

Ubiquitin-dependent proteolysis of specific target proteins is required for several important steps during the cell cycle. Degradation of such proteins is strictly cell cycle-regulated and triggered by two large ubiquitin ligases, termed anaphase-promoting complex (APC) and Skp1/Cullin/F-box complex (SCF). Here we show that yeast Ran-binding protein 1 (Yrb1p), a predominantly cytoplasmic protein implicated in nucleocytoplasmic transport, is required for cell cycle regulated protein degradation. Depletion of Yrb1p results in the accumulation of unbudded G(1) cells and of cells arrested in mitosis implying a function of Yrb1p in the G(1)/S transition and in the progression through mitosis. Temperature-sensitive yrb1-51 mutants are defective in APC-mediated degradation of the anaphase inhibitor protein Pds1p and in degradation of the cyclin-dependent kinase inhibitor Sic1p, a target of SCF. Thus, Yrb1p is crucial for efficient APC- and SCF-mediated proteolysis of important cell cycle regulatory proteins. We have identified the UBS1 gene as a multicopy suppressor of yrb1-51 mutants. Ubs1p is a nuclear protein, and its deletion is synthetic lethal with a yrb1-51 mutation. Interestingly, UBS1 was previously identified as a multicopy suppressor of cdc34-2 mutants, which are defective in SCF activity. We suggest that Ubs1p may represent a link between nucleocytoplasmic transport and ubiquitin ligase activity.
J Biol Chem 2000 Dec 08
PMID:Yeast Ran-binding protein Yrb1p is required for efficient proteolysis of cell cycle regulatory proteins Pds1p and Sic1p. 1099 51


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