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

Ubiquitin ligases play an important regulatory role in the control of protein degradation processes via the ubiquitin/26S proteasome pathway in eukaryotes. These enzymes participate in substrate specification and mediate the transfer of ubiquitin to target proteins. A large number of ubiquitin ligases are predicted in the eukaryotes whose genomes have been sequenced; in Arabidopsis thaliana more than 1300 genes are thought to encode ubiquitin ligases. At least three classes of ubiquitin ligases are present in Arabidopsis, one of which comprises about 470 RING zinc-finger domain proteins. Within this class we have characterized the ATL family that encodes a RING-H2 finger. We identified 80 members of this family in A. thaliana and 121 in Oryza sativa. About 60% of the rice ATLs are clustered with A. thaliana ATLs, and in many cases the gene products showed sequence similarities beyond the ATL's conserved features, suggesting that they could be orthologous genes. Ninety percent of the ATLs are intronless genes, suggesting that the structure of the basic ATL protein may have evolved as a functional module. We carried out a survey of T-DNA insertions in 30% of the Arabidopsis ATL genes and screened for possible phenotypes. Four of these genes are likely to be essential for viability, since homozygous plants for the T-DNA insertion were not recovered. One of them, ATL8, is mainly expressed in young siliques, suggesting a role during embryogenesis. We also recovered a line carrying a T-DNA insertion in ATL43 that showed an ABA-insensitive phenotype, suggesting a role of this gene in the ABA response. The organization of ATLs in Arabidopsis and rice in this study will be a valuable comprehensive guide for this multigene family.
J Mol Evol 2006 Apr
PMID:The ATL gene family from Arabidopsis thaliana and Oryza sativa comprises a large number of putative ubiquitin ligases of the RING-H2 type. 1655 37

Nuclear Magnetic Resonance (NMR) spectroscopy is a key experimental technique used to study protein structure, dynamics, and interactions. NMR methods face the bottleneck of spectral analysis, in particular determining the resonance assignments, which help define the mapping between atoms in the protein and peaks in the spectra. A substantial amount of noise in spectral data, along with ambiguities in interpretation, make this analysis a daunting task, and there exists no generally accepted measure of uncertainty associated with the resulting solutions. This paper develops a model-based inference approach that addresses the problem of characterizing uncertainty in backbone resonance assignment. We argue that NMR spectra are subject to random variation, and ignoring this stochasticity can lead to false optimism and erroneous conclusions. We propose a Bayesian statistical model that accounts for various sources of uncertainty and provides an automatable framework for inference. While assignment has previously been viewed as a deterministic optimization problem, we demonstrate the importance of considering all solutions consistent with the data, and develop an algorithm to search this space within our statistical framework. Our approach is able to characterize the uncertainty associated with backbone resonance assignment in several ways: 1) it quantifies of uncertainty in the individually assigned resonances in terms of their posterior standard deviations; 2) it assesses the information content in the data with a posterior distribution of plausible assignments; and 3) it provides a measure of the overall plausibility of assignments. We demonstrate the value of our approach in a study of experimental data from two proteins, Human Ubiquitin and Cold-shock protein A from E. coli. In addition, we provide simulations showing the impact of experimental conditions on uncertainty in the assignments.
Stat Appl Genet Mol Biol 2004
PMID:Model-based assignment and inference of protein backbone Nuclear Magnetic Resonances. 1664 22

1. Ubiquitin immunohistochemistry was used for investigation of time dependent changes of ubiquitin in the nerve cells reacting to ischemic/reperfusion damage. In the rabbit spinal cord ischemia model a period of 30 min ischemia followed by 24 and 72 h of reperfusion caused neuronal degeneration selectively in the ventral horn motor neurons as well as interneurons of the intermediate zone. 2. Ubiquitin aggregates were accumulated in the neurons of lamina IX and the neurons of intermediate zone destined to die 72 h after 30 min of the spinal cord ischemia. 3. The activation of ubiquitin hydrolytic system is related to a defective homeostasis and could trigger different degenerative processes. Having in mind this, we used EGb 761 to rescue the motor neurons and interneurons against ischemia/reperfusion damage. Our results show that after 30 min of ischemia and 24 or 72 h of reperfusion with EGb 761 pre-treatment for 7 days the vulnerable neurons in the intermediate zone and lamina IX exhibit marked elevation of ubiquitin-positive granules in the cytoplasm, dendrites and nuclei. Abnormal protein aggregates have not been observed in these cells. 4. The rabbits were completely paraplegic after 30 min of ischemia and 24 or 72 h of reperfusion. However, after 7 days EGb 761 pre-treatment, 30 min of ischemia and 24 or 72 h of reperfusion the animals did not show paraplegia. 5. Evaluated ubiquitin-positive neurons of the L(5)-L(6) segments showed significant decrease in number and significant increase of density after 30 min of ischemia followed by 24 h and mainly 72 h of reperfusion. Ubiquitin immunohistochemistry confirmed the protective effect of EGb 761 against ischemia/reperfusion damage in the rabbit spinal cord.
Cell Mol Neurobiol
PMID:Extract EGb 761 pretreatment limits ubiquitin positive aggregates in rabbit spinal cord neurons after ischemia-reperfusion. 1667 Sep 48

The folding pathway of common-type acyl phosphatase (ctAcP) is characterized using psi-analysis, which identifies specific chain-chain contacts using bi-histidine (biHis) metal-ion binding sites. In the transition state ensemble (TSE), the majority of the protein is structured with a near-native topology, only lacking one beta-strand and an alpha-helix. psi-Values are zero or unity for all sites except one at the amino terminus of helix H2. This fractional psi-value remains unchanged when three metal ions of differing coordination geometries are used, indicating this end of the helix experiences microscopic heterogeneity through fraying in the TSE. Ubiquitin, the other globular protein characterized using psi-analysis, also exhibits a single consensus TSE structure. Hence, the TSE of both proteins have converged to a single configuration, albeit one that contains some fraying at the periphery. Models of the TSE of both proteins are created using all-atom Langevin dynamics simulations using distance constraints derived from the experimental psi-values. For both proteins, the relative contact order of the TS models is approximately 80% of the native value. This shared value viewed in the context of the known correlation between contact order and folding rates, suggests that other proteins will have a similarly high fraction of the native contact order. This constraint greatly limits the range of possible configurations at the rate-limiting step.
J Mol Biol 2006 Aug 25
PMID:Small proteins fold through transition states with native-like topologies. 1687 94

Ubiquitin-mediated degradation of the cyclin-dependent kinase inhibitor p27 provides a powerful route for enforcing normal progression through the mammalian cell cycle. According to a current model, the ubiquitination of p27 during S-phase progression is mediated by SCF(Skp2) E3 ligase that captures Thr187-phosphorylated p27 by means of the F-box protein Skp2, which in turn couples the bound substrate via Skp1 to a catalytic core complex composed of Cul1 and the Rbx/Roc RING finger protein. Here we identify Skp2 as a component of an Skp1-cullin-F-box complex that is based on a Cul1-Ro52 RING finger B-box coiled-coil motif family protein catalytic core. Ro52-containing complexes display E3 ligase activity and promote the ubiquitination of Thr187-phosphorylated p27 in a RING-dependent manner in vitro. The knockdown of Ro52 expression in human cells with small interfering RNAs causes the accumulation of p27 and the failure of cells to enter S phase. Importantly, these effects are abrogated by the simultaneous removal of p27. Taken together, these data suggest a key role for Ro52 RING finger protein in the regulation of p27 degradation and S-phase progression in mammalian cells and provide evidence for the existence of a Cul1-based catalytic core that utilizes Ro52 RING protein to promote ubiquitination.
Mol Cell Biol 2006 Aug
PMID:Regulation of p27 degradation and S-phase progression by Ro52 RING finger protein. 1688 May 11

Ubiquitination is a post-translational modification implicated in a variety of cellular functions, including transcriptional regulation, protein degradation and membrane protein trafficking. Ubiquitin and the enzymes that act on it, although conserved and essential in eukaryotes, have not been well studied in parasites, despite sequencing of several parasite genomes. Several putative ubiquitin hydrolases have been identified in Plasmodium falciparum based on sequence homology alone, with no evidence of expression or function. Here we identify the first deubiquitinating enzyme in P. falciparum, PfUCH54, by its activity. We show that PfUCH54 also has deNeddylating activity, as assayed by a mammalian Nedd8-based probe. This activity is absent from mammalian homologues of PfUCH54. Given the importance of parasitic membrane protein trafficking as well as protein degradation in the virulence of this parasite, this family of enzymes may represent a target for pharmacological intervention with this disease.
Mol Microbiol 2006 Sep
PMID:Identification by functional proteomics of a deubiquitinating/deNeddylating enzyme in Plasmodium falciparum. 1692 53

Ubiquitin conjugation of proteins is critical for cell homeostasis and contributes to both cell survival and death. Here we studied ubiquitination of proteins in pressure overloaded (PO) myocardium in the context of cardiomyocyte survival. Analysis using a feline right ventricular pressure overload (RVPO) model revealed a robust and transient increase in ubiquitination of proteins present in the Triton X-100-insoluble fraction in 24 to 48 h PO myocardium, and confocal micrographs indicate this increase in ubiquitination occurs subsarcolemmaly near the intercalated disc area of cardiomyocytes. The ubiquitination was accompanied by changes in E3 ligases including Cbl, E6AP, Mdm2 and cIAP in the same period of PO, although atrophy-related E3 ligases, MuRF1 and MuRF3 were unaltered. Furthermore, Cbl displayed a substantial increase in both levels of expression and tyrosine phosphorylation in 48 h PO myocardium. Confocal studies revealed enrichment of Cbl at the intercalated discs of 48 h PO cardiomyocytes, as evidenced by its colocalization with N-cadherin. Although apoptosis was observed in 48 h PO myocardium by TUNEL staining, cardiomyocytes showing ubiquitin staining were not positive for TUNEL staining. Furthermore, 48 h PO resulted in the phosphorylation of inhibitor of nuclear factor kappa B (IkappaB), suggesting its ubiquitin-mediated degradation and the nuclear localization of NFkappaB for the expression of specific cell survival factors such as cIAPs. Together these data indicate that increased levels of E3 ligases that regulate cell homeostasis and promote cell survival could ubiquitinate multiple cytoskeletal protein targets and that these events that occur during the early phase of PO may contribute to both cardiomyocyte survival and hypertrophy.
J Mol Cell Cardiol 2006 Oct
PMID:Enhanced ubiquitination of cytoskeletal proteins in pressure overloaded myocardium is accompanied by changes in specific E3 ligases. 1692 82

Retroviral aspartyl proteases are homodimeric, whereas eukaryotic aspartyl proteases tend to be large, monomeric enzymes with 2-fold internal symmetry. It has been proposed that contemporary monomeric aspartyl proteases evolved by gene duplication and fusion from a primordial homodimeric enzyme. Recent sequence analyses have suggested that such "fossil" dimeric aspartyl proteases are still encoded in the eukaryotic genome. We present evidence for retention of a dimeric aspartyl protease in eukaryotes. The X-ray crystal structure of a domain of the Saccharomyces cerevisiae protein Ddi1 shows that it is a dimer with a fold similar to that of the retroviral proteases. Furthermore, the double Asp-Thr-Gly-Ala amino acid sequence motif at the active site of HIV protease is found with identical geometry in the Ddi1 structure. However, the putative substrate binding groove is wider in Ddi1 than in the retroviral proteases, suggesting that Ddi1 accommodates bulkier substrates. Ddi1 belongs to a family of proteins known as the ubiquitin receptors, which have in common the ability to bind ubiquitinated substrates and the proteasome. Ubiquitin receptors contain an amino-terminal ubiquitin-like (UBL) domain and a carboxy-terminal ubiquitin-associated (UBA) domain, but Ddi1 is the only representative in which the UBL and UBA domains flank an aspartyl protease-like domain. The remarkable structural similarity between the central domain of Ddi1 and the retroviral proteases, in the global fold and in active-site detail, suggests that Ddi1 functions proteolytically during regulated protein turnover in the cell.
J Mol Biol 2006 Dec 01
PMID:Ddi1, a eukaryotic protein with the retroviral protease fold. 1701 Mar 77

Crustacean muscle growth is discontinuous due to molt cycle. To characterize molt-related gene expression patterns, we studied the mRNA levels of molecular chaperone-ubiquitin and heat shock protein 70 (Hsp 70) in comparison with muscle protein alpha-actin and beta-actin in marine shrimp Litopenaeus vannamei. Total RNA from abdominal muscle was isolated from 3-month-old animals in six different molt stages. The mRNA levels of target genes were detected by reverse-transcriptase-multiplex PCR and expressed as the ratio to elongation factor-1alpha. Ubiquitin mRNA levels were relatively steady over all stages of the molt cycle. Hsp70 levels were not detectable in early postmolt and late premolt stages, but showed a progressive increase from late postmolt to intermolt stages. Expression levels of alpha-actin gene were lower during postmolt, reached a plateau in intermolt and remained relatively high in premolt stage. Levels of beta-actin increased progressively from postmolt to intermolt, reaching a maximum value in premolt. Therefore, the mRNAs encoding for ubiquitin and Hsp 70 in abdominal muscle did not increase significantly in premolt stages, which is typically associated with claw muscle degradation. Muscle structural alpha-actin and cytoskeletal beta-actin were increased during intermolt and premolt stages, suggesting high muscle growth during these stages in the abdominal muscle of the L. vannamei.
Mol Reprod Dev 2007 May
PMID:Expression patterns of ubiquitin, heat shock protein 70, alpha-actin and beta-actin over the molt cycle in the abdominal muscle of marine shrimp Litopenaeus vannamei. 1703 5

Ubiquitin receptor proteins play an important role in delivering ubiquitylated protein substrates to the proteasome for degradation. HHR23a and hPLIC2 are two such ubiquitin receptors that contain ubiquitin-like (UBL) domains, which interact with the proteasome, and ubiquitin-associated (UBA) domains, which interact with ubiquitin. Depending on their abundance UBL/UBA family members can either promote or inhibit the degradation of other proteins, which suggests their participation in the delivery of substrates to the proteasome is highly regulated. In previous work, we determined UBL/UBA domain interactions to promote intramolecular interactions in hHR23a that are abrogated with the addition of either ubiquitin or the proteasome component S5a. In yeast, we determined the hHR23a ortholog (Rad23) to interact with another UBL/UBA family member (Ddi1) and to bind a common tetraubiquitin chain. Here, we use NMR spectroscopy to reveal that hHR23a interacts with hPLIC2 via UBL/UBA domain interactions and to map their binding surfaces. In addition, we demonstrate that these two proteins associate in mammalian cells. Intriguingly, inhibition of the proteasome mitigates hHR23a/hPLIC2 interaction.
J Mol Biol 2007 Jan 26
PMID:Ubiquitin receptor proteins hHR23a and hPLIC2 interact. 1709 53


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