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

Ubiquitin conjugating enzymes participate in the thioester cascade that leads to protein ubiquitination. Although Ubc9 is homologous to E2 ubiquitin conjugating enzymes we have shown that it is unable to form a thioester with ubiquitin, but can form a thioester with the small ubiquitin-like protein SUMO. Thus Ubc9 is a SUMO conjugating enzyme rather than a ubiquitin conjugating enzyme. Transacetylation of Ubc9 by SUMO is not mediated by the E1 ubiquitin activating enzyme, but by a distinct enzymatic activity. SUMO conjugation to target proteins is mediated by a different, but parallel pathway to ubiquitination.
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PMID:Ubch9 conjugates SUMO but not ubiquitin. 940 37

Ubiquitin conjugation is known to target protein substrates primarily to degradation by the proteasome or via the endocytic route. Here we describe a novel protein modification pathway in yeast which mediates the conjugation of RUB1, a ubiquitin-like protein displaying 53% amino acid identity to ubiquitin. We show that RUB1 conjugation requires at least three proteins in vivo. ULA1 and UBA3 are related to the N- and C-terminal domains of the E1 ubiquitin-activating enzyme, respectively, and together fulfil E1-like functions for RUB1 activation. RUB1 conjugation also requires UBC12, a protein related to E2 ubiquitin-conjugating enzymes, which functions analogously to E2 enzymes in RUB1-protein conjugate formation. Conjugation of RUB1 is not essential for normal cell growth and appears to be selective for a small set of substrates. Remarkably, CDC53/cullin, a common subunit of the multifunctional SCF ubiquitin ligase, was found to be a major substrate for RUB1 conjugation. This suggests that the RUB1 conjugation pathway is functionally affiliated to the ubiquitin-proteasome system and may play a regulatory role.
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PMID:A novel protein modification pathway related to the ubiquitin system. 954 34

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.
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PMID:The Arabidopsis cullin AtCUL1 is modified by the ubiquitin-related protein RUB1. 1061 86

Ubiquitin/26S proteasome-dependent degradation of topoisomerase I (TOP1) has been suggested to be a unique repair response to TOP1-mediated DNA damage. In the current study, we show that treatment of mammalian cells or yeast cells expressing human DNA TOP1 with camptothecin (CPT) induces covalent modification of the TOP1 by SUMO-1/Smt3p, a ubiquitin-like protein. This conclusion is based on the following observations: (i) Mammalian DNA TOP1 conjugates induced by CPT were cross-reactive with SUMO-1/Smt3p-specific antibodies both in yeast expressing human DNA TOP1 as well as mammalian cells. (ii) The formation of TOP1 conjugates was shown to be dependent on UBC9, the E2 enzyme for SUMO-1/Smt3p. (iii) TOP1 physically interacts with UBC9. (iv) Ubc9 mutant yeast cells expressing human DNA TOP1 was hypersensitive to CPT, suggesting that UBC9/SUMO-1 may be involved in the repair of TOP1-mediated DNA damage.
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PMID:SUMO-1 conjugation to topoisomerase I: A possible repair response to topoisomerase-mediated DNA damage. 1075 68

Selective protein degradation by the ubiquitin-proteosome pathway has recently emerged as a powerful regulatory mechanism in a wide variety of cellular processes. Ubiquitin conjugation requires the sequential activity of three enzymes or protein complexes called the ubiquitin-activating enzyme (E1), the ubiquitin-conjugating enzyme (E2), and the ubiquitin-protein ligase (E3). In most eukaryotes, there are a small number of similar E1 isoforms without apparent functional specificity. The specific selection of target proteins is accomplished by the E2 and E3 proteins. One of the best-characterized families of E3s are the SCF complexes. The SCF is composed of a cullin (Cdc53), SKP1, RBX1 and one member of a large family of proteins called F-box proteins. The function of the F-box protein is to interact with target proteins. In some cases, the stability of the F-box protein may regulate activity of the SCF complex. In addition, post-translational modification of the cullin subunit by the ubiquitin-like protein RUB/NEDD8 appears to regulate SCF function. In plants, the SCF has so far been implicated in floral development, circadian clock, and response to the plant growth regulators auxin and jasmonic acid.
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PMID:F-box proteins and protein degradation: an emerging theme in cellular regulation. 1111 56

Ubiquitin-like proteins Rad23 and Dsk2 have recently been shown to be capable of binding both polyubiquitin chains and the 26S proteasome. The ubiquitin-like domains (Ubls) of Rad23 and Dsk2 are indispensable for their interaction with the 26S proteasome, but the proteasome subunits capable of binding the Ubl have not been identified. Here, we report that the Ubls of both Rad23 and Dsk2 can bind with the 19S regulatory particle (RP) of the 26S proteasome in vivo and in vitro. A competition assay using the respective Ubls of Rad23 and Dsk2 revealed that they bind to the RP in a competitive manner. The base subcomplex of the RP was found to have the ability to bind the Ubl. By cross-linking experiments, Rpn1 and Rpn2 were identified as Ubl-binding subunits. Taken together, the results suggest that the Rpn1 and Rpn2 in the base subcomplex form the receptor for the ubiquitin-like protein.
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PMID:Identification of ubiquitin-like protein-binding subunits of the 26S proteasome. 1220 Jan 20

ISG15 is a ubiquitin-like protein that is induced by interferon and microbial challenge. Ubiquitin-like proteins are covalently conjugated to cellular proteins and may intersect the ubiquitin-proteasome system via common substrates or reciprocal regulation. To investigate the relationship between ISG15 conjugation and proteasome function, we treated interferon-induced cells with proteasome inhibitors. Surprisingly, inhibition of proteasomal, but not lysosomal, proteases dramatically enhanced the level of ISG15 conjugates. The stimulation of ISG15 conjugates occurred rapidly in the absence of protein synthesis and was most dramatic in the cytoskeletal protein fraction. Inhibition of ISG15 conjugation by ATP depletion abrogated the proteasome inhibitor-dependent increase in ISG15 conjugates, suggesting that the effect was mediated by de novo conjugation, rather than protection from proteasomal degradation or inhibition of ISG15 deconjugating activity. The increase in ISG15 conjugates did not occur through a stabilization of the ISG15 E1 enzyme, UBE1L. Furthermore, simultaneous modification of proteins by both ISG15 and ubiquitin did not account for the proteasome inhibitor-dependent increase in ISG15 conjugates. These findings provide the first evidence for a link between ISG15 conjugation and proteasome function and support a model in which proteins destined for ISG15 conjugation are proteasome-regulated.
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PMID:Proteasomes modulate conjugation to the ubiquitin-like protein, ISG15. 1242 15

Several ubiquitin-like proteins recently discovered have been confirmed to modify proteins akin to ubiquitinization for fine-regulation of intracellular proteins. In the present study, we report a novel ubiquitin-like protein from human dendritic cells (DC), named as dendritic cell-derived ubiquitin-like protein (DC-UbP). The full-length of DC-UbP cDNA is 565bp and encodes 106 amino acids. Ubiquitin domain (UBQ) in DC-UbP shares 28.6% identity and 55% similarity to ubiquitin, but does not possess the conserved C-terminus Gly-Gly of ubiquitin required for ubiquitinization. DC-UbP localized in cytoplasm, especially in mitochondrion, indicating that it may play a role in mitochondrial biology. DC-UbP mRNA was expressed in various tumor cells, but not in adult human normal tissues, suggesting that DC-UbP might be related to tumor genesis. In addition, DC-UbP mRNA expression decreased in the HL60 cells undergoing apoptosis after being stimulated with TRAIL and in the differentiated HL60 cells induced by ARTA. Taken together, DC-UbP might be downregulated during cellular differentiation and apoptosis.
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PMID:Cloning and identification of a novel human ubiquitin-like protein, DC-UbP, from dendritic cells. 1250 22

DNA topoisomerase I and II have been shown to be modified with a ubiquitin-like protein SUMO in response to their specific inhibitors called 'poisons'. These drugs also damage DNA by stabilizing the enzyme-DNA cleavable complex and induce a degradation of the enzymes through the 26S proteasome system. A plausible link between sumoylation and degradation has not yet been elucidated. We demonstrate here that topoisomerase IIbeta, but not its isoform IIalpha, is selectively degraded through proteasome by exposure to the catalytic inhibitor ICRF-193 which does not damage DNA. The beta isoform immunoprecipitated from ICRF-treated cells was modified by multiple modifiers, SUMO-2/3, SUMO-1, and polyubiquitin. When the SUMO conjugating enzyme Ubc9 was conditionally knocked out, the ICRF-induced degradation of topoisomerase IIbeta did not occur, suggesting that the SUMO modification pathway is essential for the degradation.
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PMID:The SUMO pathway is required for selective degradation of DNA topoisomerase IIbeta induced by a catalytic inhibitor ICRF-193(1). 1283 72

NEDD8 is a ubiquitin-like protein that controls vital biological events through its conjugation to target proteins. Previously, we identified a negative regulator of the NEDD8 conjugation system, NEDD8 ultimate buster-1 (NUB1), that recruits NEDD8 and its conjugates to the proteasome for degradation. Recently, we performed yeast two-hybrid screening with NUB1 as bait and isolated a ubiquitin precursor UbC1 that is composed of nine tandem repeats of a ubiquitin unit through alpha-peptide bonds. Interestingly, NUB1 interacted with UbC1 through its UBA domain. Further study revealed that the UBA domain interacted with alpha-peptide bond-linked polyubiquitin, but not with isopeptide bond-linked polyubiquitin, indicating that the UBA domain of NUB1 is a specific acceptor for the linear ubiquitin precursor. A functional study revealed that an unidentified protein that was immunoprecipitated with NUB1 served as a ubiquitin C-terminal hydrolase for UbC1. Thus, NUB1 seems to form a protein complex with the unidentified ubiquitin C-terminal hydrolase and recruit UbC1 to this complex. This might allow the ubiquitin C-terminal hydrolase to hydrolyze UbC1, in order to generate ubiquitin monomers. Northern blot analysis showed that the mRNAs of both NUB1 and UbC1 were enriched in the testis. Furthermore, in situ hybridization showed that both mRNAs were strongly expressed in seminiferous tubules of the testis. These results may imply that the UbC1 hydrolysis mediated by NUB1 is involved in cellular functions in the seminiferous tubules such as spermatogenesis.
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PMID:NUB1-mediated targeting of the ubiquitin precursor UbC1 for its C-terminal hydrolysis. 1500 9


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