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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)

An analysis of the subunits of the high molecular weight proteinase, macropain (multicatalytic proteinase or proteasome) from human erythrocytes has been conducted using N-terminal amino acid sequencing, gel electrophoresis and reverse-phase peptide mapping. This analysis provided evidence for the existence of 13 subunits of different primary structure. Five subunits were susceptible to the Edman degradation and yielded unique N-terminal sequences. Similarities among these sequences, however, indicated that the subunits are homologous. Two-dimensional gel electrophoresis discriminated 10 major components, which included two of the subunits for which N-terminal sequences had been determined and eight N-terminally blocked subunits. Tryptic peptide mapping indicated that all 10 of these components have a different amino acid sequence. Tryptic peptides from some of the subunits were subjected to amino acid sequence analysis, and the data indicated that all the subunits tested in this way are related by common ancestry. The data suggest that at least nine of the total of 13 subunits are encoded by members of the same gene family; the remaining four subunits have not yet been investigated in sufficient detail to establish their relationships. No evidence for a close relationship with any previously investigated proteinase family has been found. Finally, through a comparison of the 'latent' and 'active' forms of macropain, the study established a close similarity in the subunit composition of these catalytically very different species, although proteolytic degradation of selected subunits appears in the active form of the enzyme.
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PMID:Relationships among the subunits of the high molecular weight proteinase, macropain (proteasome). 230 72

Rat liver proteasome (multicatalytic proteinase complex) is a 20S-ring shaped particle having a molecular mass of 750 kDa, and is composed of at least 13 non-identical components ranging from 21 to 31 kDa in size. We found here that the NH2-terminal residues of all the known 13 components, except for C5, are not reactive to phenylisothiocyanate. Among them, components C2, C3 and C8 are blocked in their NH2-termini with N alpha-acetyl-Met, N alpha-acetyl-Ala, and N alpha-acetyl-Ser, respectively. The NH2-terminal portions of C2, C3, and C8 exhibit sequence similarity to one another, but that of the non-blocked component C5 differs from those of C2, C3, and C8.
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PMID:The NH2-terminal residues of rat liver proteasome (multicatalytic proteinase complex) subunits, C2, C3 and C8, are N alpha-acetylated. 233 42

Proteasomes are multicatalytic proteinase complexes consisting of a set of non-identical polypeptide subunits. A cDNA for component C5 of rat proteasomes was isolated by screening a Reuber H4TG hepatoma cell cDNA library using synthetic oligodeoxynucleotide probes corresponding to partial amino acid sequences of the protein. The polypeptide deduced from the open reading frame consisted of 240 amino acid residues with a calculated molecular weight of 26,479. Computer analysis revealed little similarity of C5 to other proteins reported so far. The primary structure of C5 showed partial sequence homology to that of another component C3, but no regions of homology with the sequence of component C2. Thus C5 is concluded to be a new type of subunit of the proteasome complex.
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PMID:cDNA cloning and sequencing of component C5 of proteasomes from rat hepatoma cells. 233 47

Proteasome, a high molecular weight protease complex (HMP, approximately 600 kDa) was isolated from bovine eye lens epithelium tissue. In contrast with prior reports, lens proteasome degraded the major lens protein alpha-crystallin and S-carboxymethylated bovine serum albumin at 37 degrees C, mostly to trichloroacetic acid precipitable polypeptides. The proteasome, thus isolated, was labile at 55 degrees C. As indicated by the ability of p-chloromercuribenzoate and N-ethylmaleimide to block activity, a thiol group is required for activity. Alpha-crystallin was oxidized by exposure to 60Co-irradiation under an atmosphere of N2O (1-50 kilorads). This dose delivered 0.1-5.7 mol of hydroxyl radicals per mol of crystallin. Irradiation resulted in increased heterogeneity, aggregation, and fragmentation of the crystallin preparation. The proteolytic susceptibility of alpha-crystallin to the lens HMP was enhanced by the irradiation in a dose-dependent manner up to 20 kilorads (.OH concentration up to 2.3 mol per mol of alpha-crystallin). When 50 kilorads (5.7 mol .OH per mol of alpha-crystallin) was used, there was extensive aggregation and no enhancement in proteolysis over the unirradiated sample. The data indicate that the lens HMP can degrade mildly photooxidized lens proteins, but proteins which are extensively damaged are not degraded and may accumulate. This may be related to cataract formation.
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PMID:Lens proteasome shows enhanced rates of degradation of hydroxyl radical modified alpha-crystallin. 234 Oct 52

The nucleotide sequence of component C9 of rat proteasomes (multicatalytic proteinase complexes) has been determined from a recombinant cDNA clone isolated by screening a Reuber H4TG hepatoma cell cDNA library using synthetic oligodeoxynucleotide probes corresponding to partial amino acid sequences of the protein. The predicted sequence of C9 consists of 261 amino acid residues with a calculated molecular weight of 29,496. The C9 component is a novel protein, differing from known proteins, but its primary structure resembles those of other proteasome components, including C2, C3 and C5, although its similarity to C5 is relatively low, suggesting that proteasomes consist of a family of proteins that have evolved from a common ancestor.
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PMID:cDNA cloning and sequencing of component C9 of proteasomes from rat hepatoma cells. 235 75

The multicatalytic proteinase from human erythrocytes (macropain, proteasome) is a large enzyme composed of at least six distinct subunits ranging in molecular masses from 20 to 30 kDa. As its name implies, this proteinase appears to contain multiple catalytic sites with differing specificities toward peptide substrates. Several polycationic substances, including polylysines, polyarginine, protamine and histone H1 markedly stimulated caseinolytic activity of the proteinase. Activation was instantaneous, and involved increasing the Vmax of the proteinase for casein. Prolonged preincubation with polylysine at 37 degrees C resulted in autolytic inactivation of the proteinase. The polylysine concentrations required for half-maximal activation or autolytic inactivation were the same. A 23 kDa subunit of the proteinase disappeared at the same rate as loss of catalytic activity, and with the same pH dependence and polylysine concentration dependence. These results suggest that polylysine perturbs the structure of the multicatalytic proteinase, resulting in increased catalytic activity toward substrates; and, with prolonged exposure, allowing autoproteolytic inactivation to occur. The 23 kDa subunit appeared to be required for expression of caseinolytic activity, and may therefore be a catalytic subunit of the complex having activity against casein.
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PMID:Interaction of human erythrocyte multicatalytic proteinase with polycations. 237 99

The proteasome is a multicatalytic proteinase complex composed of nonidentical protein subunits. We have isolated a cDNA clone encoding the 35 kd proteasome subunit of Drosophila melanogaster and propose the designation PROS-35 for the corresponding gene. The deduced amino acid sequence reveals a region of striking homology to a tyrosine phosphorylation site of viral and cellular proteins suggesting a potential regulatory function for the 35 kd subunit within the proteinase complex. Immunocytochemical experiments reveal a tissue-dependent differential distribution of the proteasome between the nucleus and cytoplasm. In addition developmental analysis shows that the proteasome is highly expressed in the CNS of stage-16 embryos and in cardia, ventriculus and ovaries of adult flies. These data suggest a tissue- and development-dependent distribution of the proteasome in D. melanogaster.
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PMID:The PROS-35 gene encodes the 35 kd protein subunit of Drosophila melanogaster proteasome. 247 45

The two-dimensional electrophoretic protein subunit pattern of the proteasome, which is a mulifunctional non-lysosomal proteinase, was analyzed throughout the development of Drosophila melanogaster. The experiments show that the proteasome is already present in early embryos and its characteristic gross morphology as judged by the outer diameter of 12 nm and the inner depression of 3 nm remains unaltered. The electrophoretic analysis of the enzyme subunits demonstrates that the proteasome undergoes, dependent on development, alterations in its protein composition. The most simple subunit pattern is observed in Schneider's S-3 tissue culture cells and early embryos while with ongoing fly development the subunit pattern of the proteasome becomes increasingly complex. 32P-Labeling and immunoblotting experiments indicate that post-translational modification of the subunits must in part be responsible for the development-dependent diversification of the subunit pattern. Our data raise the possibility that the in vivo proteolytic activity and the in vivo substrate specificity of the proteasome may be regulated by modification of its subunit composition during fly development.
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PMID:The Drosophila proteasome undergoes changes in its subunit pattern during development. 249 14

In Drosophila melanogaster the population of proteasome particles consists of three distinct subclasses. By fractionation of a 40,000 x g supernatant of Drosophila homogenate on a DEAE-Sephacel column, proteasome particles which elute at salt concentrations of 200, 300, and 500 mM KAc can be separated. The proteasomes of all three subfractions sediment at 19 S in sucrose gradients and are shown by two-dimensional gel electrophoretic analysis to possess the same protein content. They differ, however, with respect to their specific proteolytic activity against the substrates benzoyl-Val-Gly-Arg-4-methylcoumaryl-7-amide, succinyl-Leu-Leu-Val-Tyr-4-methylcoumaryl-7-amide, and succinyl-Ala-Ala-Phe-4-methylcoumaryl-7-amide and the degree to which their hydrolytic activity can be enhanced by the addition of 30-110 microM sodium dodecyl sulfate (SDS). Our data show that the 200 mM proteasome fraction exhibits the lowest basal specific proteolytic activity but can be stimulated most by SDS. The 300 and 500 mM proteasome subfractions, on the other hand possess considerably higher but similar basal specific proteolytic activity. Of these only the proteolytic activity of the 300 mM subfraction against the substrates benzoyl-Val-Gly-Arg-4-methylcoumaryl-7-amide and succinyl-Leu-Leu-Val-Tyr-4-methylcoumaryl-7-amide can be enhanced by SDS. Our data raise the possibility that the different subpopulations reflect structural differences between the proteasome particles, which in turn may result in different in vivo substrate specificities of the proteasome subpopulations.
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PMID:Identification and characterization of three different subpopulations of the Drosophila multicatalytic proteinase (proteasome). 249 19

The proteasome (the multicatalytic endoproteinase complex) in mammalian tissues hydrolyzes proteins and several types of peptides. When this structure was isolated rapidly from rabbit skeletal muscle in the presence of glycerol, its various peptidase and protease activities showed a large reversible activation by physiological concentrations of ATP (Ka = 0.3-0.5 mM). Hydrolysis of succinyl-Leu-Leu-Val-Tyr-(4-methylcoumaryl-7-amide) was stimulated up to 12-fold by ATP, whereas degradation of casein and bovine serum albumin increased 4- to 7-fold. Neither ADP nor AMP had any effect. CTP, GTP, UTP, and the nonhydrolyzable analogs adenosine 5'-[beta,gamma-imino]triphosphate (AMPP[NH]P) and adenosine 5'-[alpha,beta-methylene]triphosphate (AMP[CH2]PP) increased peptide hydrolysis as well as ATP did. However, only ATP stimulated casein breakdown and only in the presence of Mg2+. Thus, nucleotide binding allows activation of the peptidase functions, but ATP hydrolysis seems necessary for enhanced degradation of proteins. The ATP effect on proteolysis was reversible and did not require ubiquitin. Sensitivity to ATP was labile, and with storage at 4 degrees C the enzyme became fully active in the absence of ATP or Mg2+. The ATP-activated form closely resembles the proteasome complex described previously, which did not show ATP dependence: both have molecular masses of 650 kDa, contain the same 8-10 subunits, and are precipitated by the same antibodies. A similar ATP-activated form was found in rabbit liver but not in rabbit reticulocytes. The proteasome seems to represent a ubiquitin-independent, ATP-stimulated proteolytic activity within nucleated mammalian cells.
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PMID:Skeletal muscle proteasome can degrade proteins in an ATP-dependent process that does not require ubiquitin. 253 33


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