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

Ubiquitin cross-reactive protein (UCRP), a 15-kDa interferon-induced protein, is a sequence homolog of ubiquitin that is covalently ligated to intracellular proteins in a parallel enzymatic reaction and is found at low levels within cultured cell lines and human tissues not exposed to interferon. Ubiquitin and UCRP ligation reactions apparently target distinct subsets of intracellular proteins, as judged from differences in the distributions of the respective adducts revealed on immunoblots. In this study, successive passages of the human lung carcinoma line A549 in the presence of neutralizing antibodies against alpha and beta interferons had no effect on the levels of either free or conjugated UCRP, indicating that these UCRP pools are constitutively present within uninduced cells and are thus not a consequence of autoinduction by low levels of secreted alpha/beta interferon. In an effort to identify potential targets for UCRP conjugation, the immunocytochemical distribution of UCRP was examined by using affinity-purified polyclonal antibodies against recombinant polypeptide. UCRP distributes in a punctate cytoskeletal pattern that is resistant to extraction by nonionic detergents (e.g., Triton X-100) in both uninduced and interferon-treated A549 cells. The cytoskeletal pattern colocalizes with the intermediate filament network of epithelial and mesothelial cell lines. Immunoblots of parallel Triton X-100-insoluble cell extracts suggest that the cytoskeletal association largely results from the noncovalent association of UCRP conjugates with the intermediate filaments rather than direct ligation of the polypeptide to structural components of the filaments. A significant increase in the sequestration of UCRP adducts on intermediate filaments accompanies interferon induction. These results suggest that UCRP may serve as a trans-acting binding factor directing the association of ligated target proteins to intermediate filaments.
Mol Cell Biol 1994 Dec
PMID:Conjugates of ubiquitin cross-reactive protein distribute in a cytoskeletal pattern. 752 57

Water oxygen-17 spin relaxation was used to study hydration and dynamics of the globular proteins bovine pancreatic trypsin inhibitor (BPTI) and ubiquitin in aqueous solution. The frequency dispersion of the longitudinal and transverse relaxation rates was measured over the Larmor frequency range 2.6 to 49 MHz in the pD range 2 to 11 at 27 degrees C. While the protein-induced relaxation enhancement was similar for the two proteins at high frequencies, it was an order of magnitude smaller for ubiquitin than for BPTI at low frequencies. This difference was ascribed to the absence, in ubiquitin, of highly ordered internal water molecules, which are known to be present in BPTI and in most other globular proteins. These observations demonstrate that the water relaxation dispersion in protein solutions is essentially due to a few structural water molecules buried within the protein matrix, but exchanging rapidly with the external water. The relaxation data indicate that the internal water molecules of BPTI exchange with bulk water on the time-scale 10(-8) to 10(-6) second thus lowering the recently reported upper bound on the residence time of these internal water molecules by four orders of magnitude, and implying that local unfolding occurs on the submicrosecond time-scale. The water molecules residing at the surface of the two proteins were found to be highly mobile, with an average rotational correlation time of approximately 20 picoseconds. For both proteins, the oxygen-17 relaxation depended only very weakly on pD, showing that ionic residues do not perturb hydration water dynamics more than other surface residues. We believe that the present results resolve the long-standing controversy regarding the mechanism behind the spin relaxation dispersion of water nuclei in protein solutions, thus establishing oxygen-17 relaxation as a powerful tool for studies of structurally and functionally important water molecules in proteins and other biomolecules.
J Mol Biol 1995 Feb 03
PMID:Protein hydration dynamics in aqueous solution: a comparison of bovine pancreatic trypsin inhibitor and ubiquitin by oxygen-17 spin relaxation dispersion. 753 Dec 48

Water deuteron (2H) spin relaxation was used to study hydrogen exchange, hydration, and protein dynamics in aqueous solutions of the globular proteins bovine pancreatic trypsin inhibitor (BPTI) and ubiquitin. The frequency dispersion of the longitudinal 2H relaxation rate was measured in the pD range 2 to 11 at 27 degrees C. In contrast to the previously reported water 17O relaxation dispersion from the same samples, the 2H dispersion depends strongly on pD. This pD dependence is due to labile protein deuterons in acidic side-chains and surface peptide groups, which exchange rapidly with water deuterons. The pD dependence of the 2H relaxation in BPTI solutions could be quantitatively accounted for in terms of known pK values and hydrogen exchange rate constants. For ubiquitin, labile protein deuterons contribute importantly to the 2H relaxation dispersion even in the neutral pD range. The 2H relaxation data also provided information about the orientational order and internal motion of OD and ND bonds in side-chains and surface peptides. A comparison of the water contribution to the 2H dispersion with the 17O dispersion indicates that one of the four internal water molecules of BPTI, presumably the deeply buried water molecule W122, exchanges more slowly (10(-6) to 10(-4) second) than the other three (10(-8) to 10(-6) second).
J Mol Biol 1995 Feb 03
PMID:Hydrogen exchange and protein hydration: the deuteron spin relaxation dispersions of bovine pancreatic trypsin inhibitor and ubiquitin. 753 Dec 49

Two new methods for the quantification and visualization of the flexibility of molecular surfaces are presented. Both methods rely on results of molecular dynamics (MD) simulations. Whereas method I is based on a simple but fast grid-counting algorithm, method II uses a mapping function that allows for a sharp and clear visualization of atomic RMS fluctuations on a molecular surface. To demonstrate the scope of the methods, MD simulations of two proteins, PTI and ubiquitin, were performed. The flexibility data are mapped onto the molecular surfaces of the proteins and visualized using texture mapping technology available on modern workstations.
J Mol Graph 1995 Apr
PMID:Quantification and visualization of molecular surface flexibility. 754 74

The 26S proteasome is the central protease of the ubiquitin-dependent pathway of protein degradation. The molecule has a molecular mass of approximately 2000 kD and has a highly conserved structure in eukaryotes. The 26S proteasome is formed by a barrel-shaped 20S core complex and two polar 19S complexes. The 20S complex has C2 symmetry and is formed by four seven-membered rings of which the outer rings (alpha-type subunits) are rotated by 25.7 degrees relative to the inner rings while the inner rings (beta-type subunits) are in register. From a comparison of the activity and regulation of the 26S and 20S particles it can be deduced that the 20S particle contains the protease activity while the 19S complex contains isopeptidase, ATPase and protein unfolding activities. In this article we describe the structures of various proteasome complexes as determined by electron microscopy and discuss structural implications of their subunit sequences.
Mol Biol Rep 1995
PMID:Structural features of archaebacterial and eukaryotic proteasomes. 756 58

Proteasomes are large multicatalytic protease complexes which fulfil central functions in major intracellular proteolytic pathways of the eukaryotic cell. 20S proteasomes are 700 kDa cylindrically shaped particles, found in the cytoplasm and the nucleus of all eukaryotes. They are composed of a pool of 14 different subunits (MW 22-25 kDa) arranged in a stack of 4 rings with 7-fold symmetry. In the yeast Saccharomyces cerevisiae a complete set of 14 genes coding for 20S proteasome subunits have been cloned and sequenced. 26S proteasomes are even larger proteinase complexes (about 1700 kDa) which degrade ubiquitinylated proteins in an ATP-dependent fashion in vitro. The 26S proteasome is build up from the 20S proteasome as core particle and two additional 19S complexes at both ends of the 20S cylinder. Recently existence of a 26S proteasome in yeast has been demonstrated. Several 26S proteasome specific genes have been cloned and sequenced. They share similarity with a novel defined family of ATPases. 20S and 26S proteasomes are essential for functioning of the eukaryotic cell. Chromosomal deletion of 20S and 26S proteasomal genes in the yeast S. cerevisiae caused lethality of the cell. The in vivo functions of proteasomes in major proteolytic pathways have been demonstrated by the use of 20S and 26S proteasomal mutants. Proteasomes are needed for stress dependent and ubiquitin mediated proteolysis. They are involved in the degradation of short-lived and regulatory proteins. Proteasomes are important for cell differentiation and adaptation to environmental changes. Proteasomes have also been shown to function in the control of the cell cycle.
Mol Biol Rep 1995
PMID:Proteasomes of the yeast S. cerevisiae: genes, structure and functions. 756 61

The proteasome (multicatalytic proteinase complex) is a large multimeric complex which is found in the nucleus and cytoplasm of eukaryotic cells. It plays a major role in both ubiquitin-dependent and ubiquitin-independent nonlysosomal pathways of protein degradation. Proteasome subunits are encoded by members of the same gene family and can be divided into two groups based on their similarity to the alpha and beta subunits of the simpler proteasome isolated from Thermoplasma acidophilum. Proteasomes have a cylindrical structure composed of four rings of seven subunits. The 26S form of the proteasome, which is responsible for ubiquitin-dependent proteolysis, contains additional regulatory complexes. Eukaryotic proteasomes have multiple catalytic activities which are catalysed at distinct sites. Since proteasomes are unrelated to other known proteases, there are no clues as to which are the catalytic components from sequence alignments. It has been assumed from studies with yeast mutants that beta-type subunits play a catalytic role. Using a radiolabelled peptidyl chloromethane inhibitor of rat liver proteasomes we have directly identified RC7 as a catalytic component. Interestingly, mutants in Pre1, the yeast homologue of RC7, have already been reported to have defective chymotrypsin-like activity. These results taken together confirm a direct catalytic role for these beta-type subunits. Proteasome activities are sensitive to conformational changes and there are several ways in which proteasome function may be modulated in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Biol Rep 1995
PMID:Catalytic components of proteasomes and the regulation of proteinase activity. 756 62

Proteasomes are large, unique protein complexes catalyzing energy- and ubiquitin-dependent proteolysis. Recent studies have revealed that these complexes are involved in two important cellular functions. One is to make antigen fragments for major histo-compatibility complex (MHC) class I-restricted antigen presentation and the other is to regulate the cell cycle by proteolysis. Here we review only the latter function of proteasomes. Proteasomes are widely distributed in eukaryotic cells, but their levels have been shown to be particularly high in various immature cells, such as cancerous, fetal and lymphoblastic cells, and agents including cell differentiation were found to suppress their expression. These conditions also regulate the expression of ubiquitin genes in a similar way, suggesting that proteasomes act ubiquitin-dependently in their 26S form in immature cells. High levels of proteasomes were found immunochemically in the nuclei of rapidly growing cells, indicating that proteasomes are important for eukaryotic cell growth. Indeed, gene disruptions of most subunits of proteasomes in yeast resulted in total suppression of cell growth and cell death. Short-lived regulatory factors of the cell cycle, such as Fos, p53, Mos, and cyclins are degraded by the proteasome-ubiquitin pathway under phosphorylated or dephosphorylated conditions. Ornithine decarboxylase, which is also a short-lived enzyme and is involved in the early phase of cell growth, is quickly degraded by proteasomes with antizyme, but without ubiquitination. Recently, we found that one of the regulatory factors of 26S proteasomes, p31, is a homologue of Nin1p, whose mutation caused inhibition of the cell cycle in yeast. These results indicate that proteasomes play important roles in regulation of the cell cycle in eukaryotes.
Mol Biol Rep 1995
PMID:Roles of proteasomes in cell growth. 756 64

The physiologic function of proteasome remains unclear. Evidence suggests a role in degradation of ubiquitin-protein conjugates, MHC antigen presentation, and some specificity of substrate within certain cell types. To explore further the properties of proteasome we have examined its effect on a well defined structure, the myofibril. We find that despite its large size (20S) proteasome is able to degrade myofibrils and intact, permeabilized muscle fibrils. The proteins degraded showed some specificity because actin, myosin and desmin were degraded faster than alpha-actinin, troponin T and tropomyosin. Changes in ultrastructure were slow and included a general loss of structure with Z and I bands effected before the M band and costameres.
Mol Biol Rep 1995
PMID:Proteolytic activity of proteasome on myofibrillar structures. 756 68

The proteolytic degradation of the inhibitory protein MAD3/I kappa B alpha in response to extracellular stimulation is a prerequisite step in the activation of the transcription factor NF-kappa B. Analysis of the expression of human I kappa B alpha protein in stable transfectants of mouse 70Z/3 cells shows that, as for the endogenous murine protein, exogenous I kappa B alpha is degraded in response to inducers of NF-kappa B activity, such as phorbol myristate acetate or lipopolysaccharide. In addition, pretreatment of the cells with the proteasome inhibitor N-Ac-Leu-Leu-norleucinal inhibits this ligand-induced degradation and, in agreement with previous studies, stabilizes a hyperphosphorylated form of the human I kappa B alpha protein. By expressing mutant forms of the human protein in this cell line, we have been able to delineate the sequences responsible for both the ligand-induced phosphorylation and the degradation of I kappa B alpha. Our results show that deletion of the C terminus of the I kappa B alpha molecule up to amino acid 279 abolishes constitutive but not ligand-inducible phosphorylation and inhibits ligand-inducible degradation. Further analysis reveals that the inducible phosphorylation of I kappa B alpha maps to two serines in the N terminus of the protein (residues 32 and 36) and that the mutation of either residue is sufficient to abolish ligand-induced degradation, whereas both residues must be mutated to abolish inducible phosphorylation of the protein. We propose that treatment of 70Z/3 cells with either phorbol myristate acetate or lipopolysaccharide induces a kinase activity which phosphorylates serines 32 and that these phosphorylations target the protein for rapid proteolytic degradation, possibly by the ubiquitin-26S proteasome pathway, thus allowing NF-kappa B to translocate to the nucleus and to activate gene expression.
Mol Cell Biol 1995 Oct
PMID:N- and C-terminal sequences control degradation of MAD3/I kappa B alpha in response to inducers of NF-kappa B activity. 756 83


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