Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

cDNA clone MS73 codes for an ATPase that is a regulatory subunit of the 26 S proteasome. Reverse transcriptase polymerase chain reaction analysis demonstrates that the expression of the gene dramatically increases in the pre-eclosion period. Western analyses show increases in other related. ATPases including MS73, MSS1, and mts2 but not TBP1. A similar increase in the 30-kDa subunit of the 20 S proteasome occurs. There are accompanying large changes in the peptidase activities of the 26 S proteasome. Relative to the 30-kDa subunit, there is no change in MSS1 and MS73, a 3-fold increase in mts2, and a 5-fold decline in TBP1. A large increase in the concentration of 26 S proteasomes together with extensive regulatory reprogramming may facilitate rapid muscular proteolysis.
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PMID:Developmental changes of the 26 S proteasome in abdominal intersegmental muscles of Manduca sexta during programmed cell death. 782 21

We have characterized a newly identified gene from Dictyostelium discoideum, DdTBP alpha, that encodes a member of the family of eukaryotic proteins. These proteins contain a conserved ATPase domain, include subunits of the 26S protease subunit, and are homologous to the mammalian human immunodeficiency virus Tat-binding protein TBP1. While information indicates that some family members are involved in the regulation of transcription in mammalian and yeast cells during growth, these proteins are also involved in other cellular functions, and nothing is known about their possible function in multicellular development. The Dictyostelium DdTBP alpha gene is developmentally regulated, with its expression at the highest levels occurring during growth and early development. The gene is present in two copies in the genome. Disruption of one copy by homologous recombination leads to aberrant morphogenesis, which lasts from the formation of the first finger until the onset of culmination. The gene appears to be essential for growth since we were unable to obtain a complete null phenotype and since expression of an inducible antisense construct in the partial null background resulted in cell death. Expression of the antisense construct during development accentuated the partial null phenotype and also resulted in very abnormal fruiting bodies. Overexpression of DdTBP alpha from its own promoter leads to very large multinucleated vegetative cells when the cells are grown in suspension culture. When the cells are plated onto petri dishes in growth medium, they rapidly split into multiple cells containing one to two nuclei, in a manner similar to that of wild-type cells. Overexpressing cells are significantly delayed in forming a multicellular aggregate, but development proceeds normally once the first finger stage is reached. The results indicate that DdTBP alpha plays an important role in regulating both growth and morphogenesis in D. discoideum.
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PMID:Growth and developmental functions of a human immunodeficiency virus Tat-binding protein/26S protease subunit homolog from Dictyostelium discoideum. 786 64

The 26 S proteasome complex catalyzing ATP-dependent breakdown of ubiquitin-ligated proteins was purified from spinach leaves to near homogeneity by chromatography on DEAE-cellulose, gel filtration on Biogel A-1.5, and glycerol density gradient centrifugation. The purified enzyme was shown to degrade multi-ubiquitinated, but not unmodified, lysozymes in an ATP-dependent fashion coupled with ATPase activity supplying energy for proteolysis and isopeptidase activity to generate free ubiquitin. By nondenaturing electrophoresis, the purified enzyme was separated into two distinct forms of the 26 S complex, named 26 S alpha and 26 S beta proteasomes, with different electrophoretic mobilities. The 26 S proteasome was found to consist of multiple polypeptides with molecular masses of 23-35 and 39-115 kDa, which were thought to be those of a 20 S proteasome with multicatalytic proteinase activity and an associated regulatory part with ATPase and deubiquitinating activities, respectively. The subunit multiplicity of the spinach 26 S proteasome closely resembled that of rat liver with minor differences in certain components. No sulfhydryl bond was involved in the assembly of this multicomponent polypeptide complex. Electron microscopy showed that the 26 S proteasome complex had a "caterpillar"-like shape, consisting of four central protein layers, assumed to be the 20 S proteasome, with asymmetric V-shaped layers at each end. These structural and functional characteristics of the spinach 26 S proteasome showed marked similarity to those of the mammalian 26 S proteasomes reported recently, suggesting that the 26 S proteasome is widely distributed in eukaryotic cells and is of general importance for catalyzing the soluble energy- and ubiquitin-dependent proteolytic pathway.
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PMID:Purification and characterization of the 26 S proteasome from spinach leaves. 792 95

PA700 is a 700,000-dalton multisubunit protein that activates multiple proteolytic activities of the 20 S proteasome by a mechanism dependent upon ATP hydrolysis (Ma, C.-P., Vu, J.H., Proske, R.J., Slaughter, C.A., and DeMartino, G.N. (1994) J. Biol. Chem. 269, 3539-3547). In order to determine the identities of and structural relationships among the subunits of PA700, individual PA700 subunits were isolated by a combination of reverse phase high performance liquid chromatography (HPLC) and SDS-polyacrylamide gel electrophoresis. Seven of the 16 subunits of PA700 so isolated were subjected to solid phase protease digestion followed by reverse phase HPLC. Selected peptides from each protein were sequenced by automated Edman degradation. Comparison of the resulting amino acid sequences with those in current data bases indicated that three of the subunits represented novel proteins, whereas four subunits were homologous to previously describe proteins. Three subunits of the latter group were, in turn, homologous to one another and are members of a large family of proteins containing a consensus sequence for ATP binding. Purified PA700 demonstrated ATPase activity. Treatment of PA700 with alkylating agents, such as N-ethylmaleimide, inhibited with similar kinetics both proteasome activation and ATPase activity, suggesting that these two activities are functionally linked. Thus, PA700 is composed of multiple members of a protein family that may function in the ATP-dependent regulation of proteasome activity.
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PMID:PA700, an ATP-dependent activator of the 20 S proteasome, is an ATPase containing multiple members of a nucleotide-binding protein family. 806 4

Plastid ORF2280 proteins from five species of land plant are shown to have limited amino-acid sequence similarity to a family of proteins that includes the yeast CDC48, SEC18, PAS1 and SUG1 proteins, three subunits of the mammalian 26S protease, and the Escherichia coli FtsH protein. These proteins all contain one or two ATPase domains and many are involved in cell division, transport of proteins across membranes, or proteolysis. Similarity with the ORF2280 proteins is restricted to a single region of about 130 amino acids that contains: (1) sequences resembling a nucleotide binding site but lacking two normally conserved residues, and (2) a downstream conserved motif with the consensus sequence VIX2TX2PX3DPALX2P. Most of the rest of ORF2280 is very poorly conserved among land plants, even though other family members such as CDC48 have slow rates of protein sequence evolution. In contrast, a protein encoded by plastid DNA of the rhodophyte alga Porphyra purpurea is very similar to E. coli FtsH. Phylogenetic analysis suggests that the red and green plastid genes are not true homologues (orthologues) but distinct members of an ancient gene family.
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PMID:Similarity between putative ATP-binding sites in land plant plastid ORF2280 proteins and the FtsH/CDC48 family of ATPases. 808 82

An ATP/ubiquitin-dependent proteasome complex with an apparent sedimentation coefficient of 26S was purified from rat liver to near homogeneity by an improved method based on procedures reported previously. Two electrophoretically distinct forms of the 26S complex, named 26S alpha and 26S beta, with very similar subunit compositions were found not only in purified preparations but also in crude extracts, indicating that the 26S proteasome is present as two isoforms. The 26S proteasome was shown to degrade multi-ubiquitinated, but not unmodified, lysozymes in an ATP-dependent fashion, to have ATPase activity supplying energy for proteolysis, and to contain isopeptidase activity to generate free ubiquitin Mg2+/ATP-dependently. The 26S proteasome also catalyzed the ATP-independent hydrolyses of three types of fluorogenic peptides with basic, neutral, and acidic amino acids at their cleavage sites, respectively. These peptides are also good substrates for the 20S proteasome, but their degradation by the free 20S proteasome and by its assembled form in the 26S complex differ markedly, suggesting a functional difference between the two forms of proteasomes. Electrophoretic and immunochemical analyses showed that the large 26S complex was composed grossly of two different structures: a core 20S proteasome with multicatalytic proteinase functions and an associated part possibly with a regulatory role. These two structures both consisted of multiple polypeptides with molecular masses of 21-31 and 35-110 kDa, respectively. The subunit multiplicity of the rat 26S proteasome closely resembled that of the human counterpart, showing only minor species-specific differences in certain components. The assembly of this multi-component complex was found not to involve a sulfhydryl bond. Electrophoretic peptide mapping with lysyl-endopeptidase indicated the non-identity of the multiple subunits of the 26S proteasome. From these structural and functional characteristics, the 26S proteasome, which is widely distributed in mammals, is suggested to be a new type of multi-molecular complex catalyzing the soluble energy- and ubiquitin-dependent proteolytic pathway.
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PMID:Purification and characterization of the 26S proteasome complex catalyzing ATP-dependent breakdown of ubiquitin-ligated proteins from rat liver. 839 72

A ubiquitin (Ub)/ATP-dependent proteolytic complex (26S proteasome) purified from rabbit skeletal muscle was dissociated into two subcomplexes, a 20S proteasome and a regulatory subunit complex, by preparative non-denaturing polyacrylamide gel electrophoresis (PAGE). The isolated regulatory subunit complex preparation gave a single broad band on analytical non-denaturing PAGE, and several bands ranging between 33 and 110 kDa on SDS-PAGE. This complex was found to consist of about 20 subunits on the basis of two-dimensional PAGE, the pattern of which appeared identical or very similar to that of the 33-110 kDa 26S proteasome subunits. The apparent molecular mass of the complex was estimated to be 1100 kDa by Ferguson plot analysis and also by Superose 6 gel filtration. Unlike the 26S proteasome, neither ATPase activity nor protease activities toward Suc-Leu-Leu-Val-Tyr-MCA, Boc-Phe-Ser-Arg-MCA, Z-Leu-Leu-Glu-beta NA, [14C]-casein, [125I]-lysozyme and Ub-[125I]-lysozyme were significantly detectable in the regulatory subunit complex. This complex was found to be capable of associating with itself in MgATP-dependent manner. These results suggest that a regulatory subunit complex dissociated from the 26S proteasome comprises all the higher molecular mass subunits of the 26S proteasome, and has no detectable ATPase and protease activities, although the homo-oligomerization occurs in an ATP-dependent fashion.
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PMID:Regulatory subunit complex dissociated from 26S proteasome: isolation and characterization. 854 9

The 26S proteasome complex plays a general role in turnover of both short and long lived proteins by specifically degrading ubiquitinated proteins. Recent evidence suggests that this large protease has more specific functions in a number of important cellular processes, ranging from activation of the transcription factor NFkB and antigen processing to transit through mitosis. We have identified a component of the 26S proteasome that interacts specifically with MB67, an orphan member of the nuclear hormone receptor superfamily. MIP224 (MB67 interacting protein) was isolated using the yeast two hybrid system and is apparently identical to the human 26S proteasome component TBP7. MIP224/TBP7 is one of several proteasomal proteins that share a strongly conserved ATPase domain (CAD) which is also present in a rapidly expanding superfamily of proteins with diverse functions. In yeast, MIP224 interacts specifically with MB67 and another closely related orphan receptor, but does not interact with several other receptor superfamily members tested. In mammalian cells, coexpression of MIP224 inhibits transactivation by MB67. MIP224 also interacts in yeast with other CAD proteins, including MSS1, which is proteasomal, and TRIP1, which is associated with transcriptional activation. This interaction of a proteasomal protein with a transcriptional protein suggests a previously unexpected link between the processes of protein degradation and transcriptional regulation.
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PMID:A component of the 26S proteasome binds on orphan member of the nuclear hormone receptor superfamily. 860 43

The activity of the intracellular protease, the proteasome, is modulated by a number of specific regulatory proteins. One such regulator, PA700, is a 700,000-Da multisubunit protein that activates hydrolytic activities of the proteasome via a mechanism that involves the ATP-dependent formation of a proteasome-PA700 complex. Four subunits of PA700 have been shown previously to be members of a protein family that contains a consensus sequence for ATP binding, and purified PA700 expresses ATPase activity. We report here the identification, purification, and initial characterization of a new modulator of the proteasome. The modulator has no direct effect on the activity of the proteasome, but enhances PA700 activation of the proteasome by up to 8-fold. This activation is associated with the formation of a proteasome/PA700-containing complex that is significantly larger than that formed in its absence. The modulator has a native Mr of approximately 300,000, as determined by gel filtration chromatography, and is composed of three electrophoretically distinct subunits with Mr values of 50,000, 42,000, and 27,000 (p50, p42, and p27, respectively). Amino acid sequence analysis of the subunits shows that p50 and p42 are members of the same ATP-binding protein family found in PA700. The p50 subunit is identical to TBP1, a protein previously reported to interact with human immunodeficiency virus Tat protein (Nelbock, P., Dillion, P. J., Perkins, A., and Rosen, C. A. (1990) Science 248, 1650-1653), while the p42 subunit seems to be a new member of the family. The p27 subunit has no significant sequence similarity to any previously described protein. Both p50 and p42, but not p27, were also identified as components of PA700, increasing the number of ATP-binding protein family members in this complex to six. Thus, p50 and p42 are subunits common to two protein complexes that regulate the proteasome. The PA700-dependent proteasome activator represents a new member of a growing list of proteins that regulate proteasome activity.
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PMID:Identification, purification, and characterization of a PA700-dependent activator of the proteasome. 862 9

We have isolated a new type of ATP-dependent protease from Escherichia coli. It is the product of the heat-shock locus hslVU that encodes two proteins: HslV, a 19-kDa protein similar to proteasome beta subunits, and HslU, a 50-kDa protein related to the ATPase ClpX. In the presence of ATP, the protease hydrolyzes rapidly the fluorogenic peptide Z-Gly-Gly-Leu-AMC and very slowly certain other chymotrypsin substrates. This activity increased 10-fold in E. coli expressing heat-shock proteins constitutively and 100-fold in cells expressing HslV and HslU from a high copy plasmid. Although HslV and HslU could be coimmunoprecipitated from cell extracts of both strains with an anti-HslV antibody, these two components were readily separated by various types of chromatography. ATP stimulated peptidase activity up to 150-fold, whereas other nucleoside triphosphates, a nonhydrolyzable ATP analog, ADP, or AMP had no effect. Peptidase activity was blocked by the anti-HslV antibody and by several types of inhibitors of the eukaryotic proteasome (a threonine protease) but not by inhibitors of other classes of proteases. Unlike eukaryotic proteasomes, the HslVU protease lacked tryptic-like and peptidyl-glutamyl-peptidase activities. Electron micrographs reveal ring-shaped particles similar to en face images of the 20S proteasome or the ClpAP protease. Thus, HslV and HslU appear to form a complex in which ATP hydrolysis by HslU is essential for peptide hydrolysis by the proteasome-like component HslV.
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PMID:HslV-HslU: A novel ATP-dependent protease complex in Escherichia coli related to the eukaryotic proteasome. 865 Jan 74


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