Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.25.1 (proteasome)
 28,817 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human proteasomes consist of 14 major subunits which can be resolved by two-dimensional polyacrylamide gel electrophoresis. Tryptic peptides from the subunits were sequenced. This allowed identification of all proteins in two-dimensional electrophoresis gels with proteasome subunits whose sequences are known from cDNA. The results also precisely define the specificity of a panel of subunit-specific monoclonal antibodies. A new proteasome subunit (Z) was discovered. In contrast, the putative subunit MECL-1 could not be detected in human placenta proteasomes.
Biochem Biophys Res Commun 1994 Dec 30
PMID:Human proteasome subunits from 2-dimensional gels identified by partial sequencing. 786 93

Two high molecular mass proteinases, multicatalytic proteinase (MCP) and a new high molecular mass proteinase (HMP) with only chymotrypsin-like activity (Khan et al. (1994) J. Biol. Chem. 269, 10016-10021) from human erythrocyte membranes, have been compared. For this purpose, MCP was purified from human erythrocyte membranes in the active form towards synthetic peptide substrates; it also hydrolysed the protein substrates [14]methyl casein and [14C]oxidised insulin beta chain at 37 degrees C. MCP from plasma membranes exhibited hollow cylindrical structures also typical of cytosolic forms. Radiolabelled diisopropyl fluorophosphate, [3H]DFP, a serine proteinase inhibitor, labelled a band of Mr 23 000 in membrane MCP. By contrast, no labelling was obtained with HMP. Chymotrypsin-like activity of HMP was also found to be insensitive to DFP. On the other hand, DFP inhibited chymotrypsin-like and peptidylglutamyl peptide hydrolysing activities of membrane MCP, with no effect on its trypsin-like activity. The inhibition of MCP by DFP was concentration-dependent. These studies showed that MCP and HMP represent two distinct kinds of proteinases with chymotrypsin-like activities and can be distinguished by the serine proteinase inhibitor DFP.
Biochim Biophys Acta 1994 Dec 14
PMID:Membrane-bound high molecular mass proteinases from human erythrocytes. 781 93

Intracellular proteins ligated to ubiquitin are degraded by the 26 S proteasome which is composed of the 20 S proteasome and a regulatory subunit complex. We have reported that ATP-dependent activity of the proteasome is activated periodically during the ascidian mitotic division cycle. In the present study, we examined changes in the activities and in the amounts of proteasomes during progression of the ascidian meiotic division cycle. During the metaphase-anaphase transition triggered by treatment with calcium ionophore, the activity of 26 S proteasome was found to be enhanced transiently and then decreased. The change in proteasome activity was completely abolished by pretreatment with a cell-permeable calcium chelating agent, BAPTA-AM, which indicates that proteasome activity is regulated by intracellular calcium mobilization. By immunoblot analyses, it was demonstrated that the 26 S proteasome underwent a change in amount in a manner similar to the change in its activities. The immunoblot analyses also indicated an inverse relation between the level of the 26 S proteasome and that of the 20 S proteasome throughout the cycle. These results, together with the fact that total amounts of the 26 S and 20 S proteasomes remain constant throughout the cycle, suggest that 26 S proteasome activity is regulated through interconversion between the 26 S and 20 S proteasomes induced by intracellular calcium mobilization during the meiotic metaphase-anaphase transition.
Dev Biol 1994 Dec
PMID:Intracellular calcium mobilization regulates the activity of 26 S proteasome during the metaphase-anaphase transition in the ascidian meiotic cell cycle. 781 81

We have cloned an Aspergillus nidulans gene (prtA) encoding an alkaline protease (Alp) by probing an A. nidulans library with a fragment amplified from an Aspergillus oryzae Alp-encoding gene. The nucleotide (nt) sequence of prtA was determined. The structure of prtA is similar to that of the A. oryzae Alp-encoding gene. The prtA gene is composed of four exons which are separated by three introns of 59, 57 and 54 nt. The deduced amino acid sequence of the prtA product shows a high degree of similarity to proteases from A. oryzae, A. fumigatus and A. flavus. Southern blot analysis suggests that only one copy of this gene is found in the genome of A. nidulans. The extracellular proteases of A. nidulans are regulated by nitrogen, carbon and sulfur metabolite repression. The prtA RNA levels were analysed under different nutrient conditions. No prtA transcript was detected in mycelium grown in medium containing glucose, NH4+ and sulfate. However, prtA transcript levels were high in mycelia transferred to medium lacking a nitrogen, carbon or sulfur source.
Gene 1994 Dec 15
PMID:Isolation and characterization of an Aspergillus nidulans gene encoding an alkaline protease. 782 93

Prosomes [or proteasomes, Multi-Catalytic Proteinase (MCP) are multisubunit protein complexes, found from archaebacteria to man, the structure of which (a 4-layer cylinder) is remarkable conserved. They were first observed as subcomplexes of untranslated mRNP, and then as a multicatalytic proteinase with several proteolytic activities. A number of sequences from subunits of these complexes are now available. Analysis of the sequences shows that these subunits are evolutionarily related, and reveals three highly conserved amino acid stretches. Based on a phylogenic approach, we propose to classify the sequenced subunits into 14 families, which fall into two superfamilies, of the alpha- and beta-type. These data, together with several recently published observations, suggest that some subunits may be interchangeable within the complexes, which would thus constitute a population of heterogenous particles.
Mol Gen Genet 1994 Dec 15
PMID:Phylogenic relationships of the amino acid sequences of prosome (proteasome, MCP) subunits. 783 Jul 25

The monocyte chemotactic protein-1 (MCP-1) is a 76 amino acid protein that specifically attracts monocytes. The expression of MCP-1 gene can be induced by lipopolysaccharides (LPS), phorbol esters (TPA) and several cytokines. However, how they regulate MCP-1 gene expression is not known. We tested whether the two putative TPA-responsive elements (TREs) and one kappa B enhancer-like region found in the MCP-1 promoter region, are involved in this regulation of MCP-1 gene expression. The 5' untranslated region of MCP-1 gene was linked to chloramphenicol acetyl transferase (CAT) reporter gene and transfected into human glioblastoma cells in which endogenous MCP gene expression was found to be stimulated by TPA and tumor necrosis factor-alpha (TNF-alpha). The 128 bp 5'-flanking region containing one TRE was adequate for basal promoter activity but the presence of both TREs in the MCP-1 promoter region were needed to give TPA responsive enhancement (2.5 fold) of expression of the marker gene. Mutations in either of the TRE's could abolish the TPA induction of CAT expression. Replacement of the kappa B enhancer-like element with a TRE-like sequence caused a 10-fold enhancement of CAT expression by TPA treatment. Random mutation of kappa B enhancer-like element did not affect CAT expression or its TPA induction. None of the MCP promoter constructs showed significant increase in CAT expression by treatment with tumor necrosis factor-alpha (TNF-alpha). This result suggested that the TNF regulation of MCP-1 gene involves other parts of the gene besides the proximal 5' flanking region.
Mol Cell Biochem 1994 Dec 21
PMID:Functional role of the cis-acting elements in human monocyte chemotactic protein-1 gene in the regulation of its expression by phorbol ester in human glioblastoma cells. 789 69

Among the roles of mediators damaging the respiratory epithelium in patients with cystic fibrosis (CF) during the course of chronic, purulent bronchitis, that of neutrophil proteases is well established. The role of bacterial proteases is less well known. Among all pathogens colonizing the airways in CF, Pseudomonas aeruginosa is quantitatively the dominant pathogen; Staphylococcus aureus and Haemophilus influenzae are present in lower numbers. Anaerobic bacteria may be detected in numbers exceeding those of Staphylococcus aureus and Haemophilus influenzae. Among all enzymes secreted by these bacterial strains, Pseudomonas elastase and alkaline protease were shown to be secreted in vivo over prolonged periods in the airways. These enzymes, mainly elastase, have proteolytic activity on many proteins involved in host defense mechanisms, often the same as those hydrolyzed by neutrophil proteases. Pseudomonas elastase has damaging effects on the respiratory epithelium; it has recently also been shown to augment the permeability of the respiratory epithelium cultured in vitro by proteolytic attack of tight junctions. The potential role of proteases and other enzymes secreted by anaerobic bacteria has not been studied in this disease. In conclusion, bacterial proteases secreted in vivo may play a role in the pathogenesis of the airway disease in CF; their relative importance to the role of host proteases is, however, often difficult to determine.
Am J Respir Crit Care Med 1994 Dec
PMID:The role of bacterial proteases in the pathogenesis of cystic fibrosis. 795 46

To investigate the pathogenicity of Aspergillus fumigatus mutants lacking putative virulence factors, we have developed a new murine model of invasive pulmonary aspergillosis based on neutropenia, the major factor predisposing patients to this infection. Mice were treated with cyclophosphamide and inoculated by the intranasal route with 5 x 10(3) conidia, a significant reduction from inoculum levels used in previous models. Evidence for the production of the extracellular alkaline protease (Alp) in lung tissue was obtained by using a fungal transformant harboring an alp::lacZ reporter gene fusion. The pathogenicities of single mutant strains lacking either Alp or the ribotoxin restrictocin and of a double mutant strain lacking both proteins were assessed in this infection model. There were no significant differences between the mutant and the wild-type strains in terms of mortality or histological-features. Inoculations with mixtures of conidia showed that the double mutant strain is slightly less virulent than the wild-type strain. We conclude that Alp and restrictocin are not important virulence determinants in pulmonary infection.
Infect Immun 1994 Dec
PMID:Virulence of Aspergillus fumigatus double mutants lacking restriction and an alkaline protease in a low-dose model of invasive pulmonary aspergillosis. 796 Jan 1

PA28, one of a series of a positive allosteric regulators of the 20 S proteasome, stimulates the enzyme's peptidase activities in an ATP-independent manner by binding to the terminal rings of the 20 S complex. PA28 has a native molecular mass of 180,000 Da and contains at least six subunits of approximately 28,000 Da. In this study we show that PA28 prepared from bovine heart contains two different subunits separable by reverse phase high performance liquid chromatography and that these subunits occur in approximately equal abundance. The subunits display mass values of 27,290 +/- 3.7 and 28,606 +/- 2.8 Da by electrospray mass spectrometry, showing that they differ in covalent structure. Partial amino acid sequence analysis of the subunits indicates that the subunits are the products of two different but homologous genes. A pair of subunits has also been isolated from rabbit heart, and partial amino acid sequence analysis shows each to be homologous to the corresponding subunit in bovine tissues. This indicates that the genes encoding two different polypeptide components of PA28 have been conserved during evolution and suggests the possibility that the two subunits play functionally distinct roles. Isolation of complexes formed between purified PA28 and the 20 S proteasome using density gradient centrifugation reveals that both PA28 subunits bind to the proteasome, indicating that both are components of functional PA28 molecules. These results are consistent with two alternative models for the subunit structure of PA28. There may exist two different PA28 molecules that are homooligomers of the 27,290- and 28,606-Da subunits, respectively. Alternatively, PA28 oligomers may contain mixtures of the 27,290- and 28,606-Da subunits either of fixed or variable stoichiometry.
J Biol Chem 1994 Dec 16
PMID:PA28, an activator of the 20 S proteasome, is composed of two nonidentical but homologous subunits. 798 12

The proteasome is a multisubunit 20 S proteinase complex involved in ubiquitin-dependent and -independent intracellular protein metabolism. Individual subunits of the alpha- and beta-type share extensive sequence homology and are encoded as members of two related and evolutionarily conserved gene families. Due to the lack of viable deletion mutants of essential alpha-type proteasome subunits in higher eukaryotes, an identification and analysis of potentially homologous subunits of different species was so far not possible. It is shown here that the novel Drosophila alpha-type Dm25 subunit can be incorporated into mouse proteasomes of stably transfected NIH 3T3 cells. The Dm25 subunit is able to substitute the mouse MC3 alpha-type subunit in proteasomes, indicating a high structural and possibly also functional homology of the two subunits. In contrast and pointing at the importance of the slightly hydrophobic N-terminal region stabile expression of a Dm25 subunit, which is truncated at its N terminus and lacks PROS box I, results in a subunit which cannot be incorporated into mouse proteasomes. The ability to form hybrid proteasomes involving essential nondeletable subunits now opens the possibility for structural and also functional analysis of such subunits by mutagenesis in higher eukaryotes.
J Biol Chem 1993 Dec 05
PMID:Drosophila proteasome Dm25 subunit substitutes the mouse MC3 subunit in hybrid proteasomes. The N-terminal domain is essential for subunit incorporation. 824 93


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