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

Ubiquitination is used to target both normal proteins for specific regulated degradation and misfolded proteins for purposes of quality control destruction. Ubiquitin ligases, or E3 proteins, promote ubiquitination by effecting the specific transfer of ubiquitin from the correct ubiquitin-conjugating enzyme, or E2 protein, to the target substrate. Substrate specificity is usually determined by specific sequence determinants, or degrons, in the target substrate that are recognized by the ubiquitin ligase. In quality control, however, a potentially vast collection of proteins with characteristic hallmarks of misfolding or misassembly are targeted with high specificity despite the lack of any sequence similarity between substrates. In order to understand the mechanisms of quality control ubiquitination, we have focused our attention on the first characterized quality control ubiquitin ligase, the HRD complex, which is responsible for the endoplasmic reticulum (ER)-associated degradation (ERAD) of numerous ER-resident proteins. Using an in vivo cross-linking assay, we directly examined the association of the separate HRD complex components with various ERAD substrates. We have discovered that the HRD ubiquitin ligase complex associates with both ERAD substrates and stable proteins, but only mediates ubiquitin-conjugating enzyme association with ERAD substrates. Our studies with the sterol pathway-regulated ERAD substrate Hmg2p, an isozyme of the yeast cholesterol biosynthetic enzyme HMG-coenzyme A reductase (HMGR), indicated that the HRD complex discerns between a degradation-competent "misfolded" state and a stable, tightly folded state. Thus, it appears that the physiologically regulated, HRD-dependent degradation of HMGR is effected by a programmed structural transition from a stable protein to a quality control substrate.
Mol Cell Biol 2001 Jul
PMID:In vivo action of the HRD ubiquitin ligase complex: mechanisms of endoplasmic reticulum quality control and sterol regulation. 1139 Jun 56

We have previously shown by RNA gel blot analyses that the tobacco polyubiquitin-encoding gene Ubi.U4 is expressed in a complex pattern during plant development (Genschik et al., 1994). In order to study its tissue-specific expression, we cloned the fragment containing the -263 bp proximal promoter of the gene, the leader intron and the first ubiquitin monomer in front of the reporter GUS gene. Histochemical analyses for GUS activity during tobacco plant development revealed that the gene is expressed at variable amounts in many plant tissues with high levels in metabolically active and/or dividing cells and in the vascular tissues of the plant. We also analysed the expression pattern of constructs in which either the intron or the intron together with the first ubiquitin monomer were deleted. Our results indicate that the ubiquitin leader intron is not only a quantitative determinant of gene expression but may also influence the tissue-specific expression pattern.
Plant Mol Biol 2001 Apr
PMID:Effects of the polyubiquitin gene Ubi. U4 leader intron and first ubiquitin monomer on reporter gene expression in Nicotiana tabacum. 1143 Apr 28

In Galleria mellonella, the pupal-adult transformation of epidermal cells is initiated at day 1 after pupal ecdysis by downregulation of pupal syntheses and loss of juvenile hormone (JH) sensitivity, indicating the change from pupal to adult commitment. To trace regulatory events as close as possible to the early steps of this process, we have analyzed, by differential display, changes in epidermal mRNA populations during the first day after pupal ecdysis in normal development as well as after JH injection. We isolated and cloned 20 cDNA 3'-fragments that are differentially expressed with regard to their developmental profile either in normal development or after injection of JH. Four clones could be verified by Northern blot hybridization. Screening of corresponding cDNA libraries with digoxigenin-labeled anti-sense mRNA probes yielded two full-length cDNA clones (9/27 and 23/86). Both of them represent genes that could be involved in the regulatory events during initiation of pupal metamorphosis or in the action of JH, respectively. The 9/27 mRNA is inducible by JH. It contains, in the 3' untranslated region, a consensus sequence for deadenylation and specific degradation. The corresponding protein possesses two PKC phosphorylation sites and is with high probability a nuclear protein. The 23/86 clone represents polyubiquitin, differentially regulated in normal development and after JH application.
Insect Biochem Mol Biol 2002 Feb
PMID:Differentially expressed genes in metamorphosis and after juvenile hormone application in the pupa of Galleria. 1175 54

The ability to destroy a particular protein at a particular time is central to the regulation of many cellular processes. Selective proteolysis in eukaryotic cells is carried out primarily by the ubiquitin-proteasome pathway. Attachment of a ubiquitin polymer to an unwanted protein causes it to be degraded by the proteasome. Several classes of enzyme, known as E1s, E2s and E3s, control the stepwise formation of a ubiquitin-protein conjugate. The specificity of substrate selection lies with the E2s and E3s. Here we describe the cloning of a Drosophila E2 gene, UbcD4, which is only expressed in embryos. Its expression pattern in stage 10-11 embryos suggests a role in germ cell development. UbcD4 can interact with the polyubiquitin-binding subunit of the proteasome.
Mol Genet Genomics 2002 Feb
PMID:UbcD4, a ubiquitin-conjugating enzyme in Drosophila melanogaster expressed in pole cells. 1186 84

Ubiquitin-mediated degradation targets cell cycle regulators for proteolysis. Much of the ubiquitin pathway's substrate specificity is conferred by E3 ubiquitin ligases, and cullins are core components of some E3s. CUL-4A encodes one of six mammalian cullins and is amplified and/or overexpressed in breast cancer, which suggests a role in regulating cell cycle progression. To examine CUL-4A's physiologic function, we generated a CUL-4A deletion mutation in mice. No viable CUL-4A(-/-) pups and no homozygous mutant embryos as early as 7.5 days postcoitum (dpc) were recovered. However, CUL-4A(-/-) blastocysts are viable, hatch, form an inner cell mass and trophectoderm, and implant (roughly 4.5 dpc), indicating that CUL-4A(-/-) embryos die between 4.5 and 7.5 dpc. Despite 87% similarity between the Cul-4A and Cul-4B cullins, the CUL-4A(-/-) lethal phenotype indicates that CUL-4A has one or more distinct function(s). Surprisingly, 44% fewer heterozygous pups were recovered than expected by Mendelian genetics, indicating that many heterozygous embryos also die during gestation due to haploinsufficiency. Taken together, our findings indicate that appropriate CUL-4A expression is critical for early embryonic development.
Mol Cell Biol 2002 Jul
PMID:CUL-4A is critical for early embryonic development. 1207 29

The polymeric ubiquitin (poly-u) genes are composed of tandem 228-bp repeats with no spacer sequences between individual monomer units. Ubiquitin is one of the most conserved proteins known to date, and the individual units within a number of poly-u genes are significantly more similar to each other than would be expected if each unit evolved independently. It has been proposed that the rather striking similarity among poly-u monomers in some lineages is caused by a series of homogenization events. Here we report the sequences of the polyubiquitin-C (Ubc) genes in two mouse strains. Analysis of these sequences, as well as those of the previously reported Chinese hamster and rat poly-u genes, supports the assertion that the homogenization of the ubiquitin-C gene in rodents is due to unequal crossing-over events. The sequence divergence of noncoding DNA was used to estimate the frequency of unequal crossing-over events (6.3 x 10(-5) events per generation) in the Ubc gene, as well as to provide evidence of apparent selection in the poly-u gene.
J Mol Evol 2002 Aug
PMID:Evolution of the mouse polyubiquitin-C gene. 1210 96

Stable and efficient germ-line transformation was achieved in the South American malaria vector, Anopheles albimanus, using a piggyBac vector marked with an enhanced green fluorescent protein gene regulated by the Drosophila melanogaster polyubiquitin promoter. Transgenic mosquitoes were identified from four independent experiments at frequencies ranging from 20 to 43% per fertile G0. Fluorescence was observable throughout the body of larvae and pupae, and abdominal segments of adults. Transgenic lines analysed by Southern hybridization had one to six germ-line integrations, with most lines having three or more integrations. Hybridized transposon vector fragments and insertion site sequences were consistent with precise piggyBac-mediated integrations, although this was not verified for all lines. The piggyBac/PUbnlsEGFP vector appears to be a robust transformation system for this anopheline species, in contrast to the use of a piggyBac vector in An. gambiae. Further tests are needed to determine if differences in anopheline transformation efficiency are due to the marker systems or to organismal or cellular factors specific to the species.
Insect Mol Biol 2002 Aug
PMID:Germ-line transformation of the South American malaria vector, Anopheles albimanus, with a piggyBac/EGFP transposon vector is routine and highly efficient. 1214 93

The highly conserved Ubiquitin proteins are expressed from genes with strong, constitutively active promoters in many species, making these promoters attractive candidates for use in driving transgene expression. Here we report the cloning and characterization of the Tribolium castaneum Polyubiquitin (TcPUb) gene. We placed the TcPUb promoter upstream of the coding region of the T. castaneum eye-colour gene Tc vermilion (Tcv) and injected this construct into embryos from a Tcv-deficient strain. Transient expression of Tcv during embryogenesis resulted in complete rescue of the larval mutant phenotype. We then incorporated the TcPUb-Tcv chimera into a piggyBac donor. Resulting germline transformants were easily recognized by rescue of eye pigmentation, illustrating the potential of the TcPUb promoter for use in driving transgene expression.
Insect Mol Biol 2002 Oct
PMID:Transgene expression from the Tribolium castaneum Polyubiquitin promoter. 1223 May 39

Because polyubiquitin chain structure modulates Ub-mediated signaling, knowledge of the physiological conformations of chain signals should provide insights into specific recognition. Here, we characterized the solution conformations of K48-linked Ub(2) and Ub(4) using a combination of NMR techniques, including chemical shift mapping of the interdomain interface, domain orientation measurements on the basis of 15N relaxation and residual dipolar couplings, and the solvent accessibility studies. Our data indicate a switch in the conformation of Ub(2), from open to closed, with increasing pH. The closed conformation features a well-defined interface that is related to, but distinguishable from, that observed in the Ub(2) crystal structure. This interface is dynamic in solution, such that important hydrophobic residues (L8, I44, V70) that are sequestered at the interface in the closed conformation may be accessible for direct interactions with recognition factors. Our results suggest that the distal two units of Ub(4), which is the minimum signal for efficient proteasomal degradation, may adopt the closed Ub(2) conformation.
J Mol Biol 2002 Dec 06
PMID:Structural properties of polyubiquitin chains in solution. 1246 May 67

Ubiquitin is a 76 amino acid protein with a remarkable degree of evolutionary conservation. Ubiquitin plays an essential role in a large number of eukaryotic cellular processes by targeting proteins for proteasome-mediated degradation. Most ubiquitin genes are found as head-to-tail polymers whose products are posttranslationally processed to ubiquitin monomers. We have characterized polyubuiquitin genes from the photosynthetic amoeboflagellate Chlorarachnion sp. CCMP 621 (also known as Bigelowiella natans) and found that they deviate from the canonical polyubiquitin structure in having an amino acid insertion at the junction between each monomer, suggesting that polyubiquitin processing in this organism is unique among eukaryotes. The gene structure indicates that processing likely cleaves monomers at the amino terminus of the insertion. We examined the phylogenetic distribution of the insertion by sequencing polyubiquitin genes from several other eukaryotic groups and found it to be confined to Cercozoa (including Chlorarachnion, Lotharella, Cercomonas, and Euglypha) and Foraminifera (including Reticulomyxa and Haynesina). This character strongly suggests that Cercozoa and Foraminifera are close relatives and form a new "supergroup" of eukaryotes.
Mol Biol Evol 2003 Jan
PMID:A novel polyubiquitin structure in Cercozoa and Foraminifera: evidence for a new eukaryotic supergroup. 1251 7


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