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

We previously presented evidence that a Z-Phe-Ser-argininal-susceptible protease which is involved in oocyte maturation of the starfish, Asterina pectinifera is the proteasome (Takagi Sawada et al, Dev. Biol. 150, 414-418 (1992)). In the present study, we investigated the timing of the function of and the role of the protease in oocyte maturation using Z-Phe-Ser-argininal. By adding the inhibitor in maturing oocytes at various times after 1-methyladenine treatment, the inhibitory ability was markedly reduced in half the time required for germinal vesicle breakdown. Furthermore, the inhibitor potently blocked the activation of histone H1 kinase and the dephosphorylation of cdc2 kinase during oocyte maturation. These results indicate that the Z-Phe-Ser-argininal-susceptible protease, probably the proteasome, plays a key role in the step of the signal transduction pathway that triggers the dephosphorylation of cdc2 kinase in response to the maturation-inducing hormone.
Biochem Mol Biol Int 1997 Apr
PMID:Protease triggers dephosphorylation of cdc2 kinase during starfish oocyte maturation. 913 20

The maturation of the eukaryotic 20 S proteasome complex occurs via 13 S and 16 S precursor complexes in a multistep assembly pathway. These precursor complexes contain alpha-subunits as well as unprocessed beta-subunit proproteins. We have purified and characterized the different proteasome assembly intermediates and analysed their ability to support beta-subunit proprotein processing in vitro. Our data show that 13 S and 16 S proteasome precursor complexes differ not only in size but also in their protein content and behaviour during hydrophobic chromatography. By establishing conditions which allowed us to analyse beta-prosubunit maturation in vitro we demonstrate that the processing of the homologous proproteins of the beta-subunits LMP2 and delta essentially takes place in 16 S precursor complexes. No proprotein processing activity was observed in 13 S precursor complexes. Furthermore, proprotein processing in vitro can be inhibited with a proteasome specific inhibitor, but with different efficiency for LMP2 and delta. A peptide, which represents the sequence of the proprotein processing site HGTT, exhibited no inhibitory effect on the processing of either subunit. These data provide further evidence that proprotein processing occurs via an autocatalytic mechanism. Our experiments also demonstrate that the chaperone protein hsc73 is associated with 16 S but not with 13 S precursor complexes. In support of the specificity of this interaction incubation with ATP leads to the dissociation of hsc73 from 16 S complexes and to the formation of high molecular weight aggregates. Prosubunit processing in isolated 16 S complexes does not, however, result in the formation of proteolytically active 20 S proteasomes which may be due to the fact that not all beta-subunits can be efficiently processed in vitro. In contrast to previous assumptions subunit processing and formation of proteolytic activity do not coincide and final 20 S complex assembly seems to represent in part a separate event which requires additional factors or proteins which are not present or active in the purified 16 S precursor complexes.
J Mol Biol 1997 Apr 25
PMID:Maturation of mammalian 20 S proteasome: purification and characterization of 13 S and 16 S proteasome precursor complexes. 914 44

Three kinds of cDNAs encoding 26S proteasome subunits have been cloned from spinach (Spinacia oleracea L.). These genes, designated as SOPSC8, SOPSC1 and SOPRS7, encode an alpha-type and a beta-type subunit of the 20S catalytic core, and an ATPase subunit of the 19/22S regulatory complex, respectively. The deduced protein sequences showed high sequence similarities to other proteasome alpha- and beta-type and ATPase subunit proteins. Southern blot analysis indicates that there are additional members of these dispersed proteasome families in the spinach genome. These three subunit genes are expressed simultaneously during germination and reach a maximum one day after sowing followed by a decline. The expression of these genes also increases during cotyledon senescence.
Plant Mol Biol 1997 May
PMID:Characterization of 26S proteasome alpha- and beta-type and ATPase subunits from spinach and their expression during early stages of seedling development. 920 46

The 26S proteasome is an eukaryotic ATP-dependent, dumbbell-shaped protease complex with a molecular mass of approximately 2000 kDa. It consists of a central 20S proteasome, functioning as a catalytic machine, and two large V-shaped terminal modules, having possible regulatory roles, composed of multiple subunits of 25-110 kDa attached to the central portion in opposite orientations. The primary structures of all the subunits of mammalian and yeast 20S proteasomes have been determined by recombinant DNA techniques, but structural analyses of the regulatory subunits of the 26S proteasome are still in progress. The regulatory subunits are classified into two subgroups, a subgroup of at least 6 ATPases that constitute a unique multi-gene family encoding homologous polypeptides conserved during evolution and a subgroup of approximately 15 non-ATPase subunits, most of which are structurally unrelated to each other.
Mol Biol Rep 1997 Mar
PMID:The 26S proteasome: subunits and functions. 922 74

We have investigated three aspects of nucleotide usage by the 26S proteasome and its regulatory complex (RC). Both particles hydrolyze the four major ribonucleotides, but ATP and CTP have substantially lower Kms for hydrolysis than do GTP and UTP. The Km for ATP hydrolysis is 15 microm for the 26S proteasome and 30 microm for the regulatory complex. Formation of the 26S proteasome from the RC and the 20S proteasome requires about 5 microm ATP. Although measurable degradation of Ubiquitin(Ub)-lysozyme conjugates occurs in the presence of CTP, GTP, and UTP, the best nucleotide for Ub-conjugate degradation by the 26S proteasome is ATP, with an estimated Km of 12 microm. In summary, our studies show that micromolar concentrations of ATP are sufficient for several 26S proteasome activities.
Mol Biol Rep 1997 Mar
PMID:Effects of nucleotides on assembly of the 26S proteasome and degradation of ubiquitin conjugates. 922 75

The 26S proteasome is a 2-Megadalton proteolytic complex with over 30 distinct subunits. The 19S particle, a subcomplex of the 26S proteasome, is thought to confer ATP-dependence and ubiquitin-dependence on the proteolytic core particle of the proteasome. Given the complexity of the 19S particle, genetic approaches are likely to play an important role in its analysis. We have initiated biochemical and genetic studies of the 19S particle in Saccharomyces cerevisiae. Here we describe the localization to the proteasome of several ATPases that were previously proposed to be involved in transcription. Independent studies indicate that the mammalian 26S proteasome contains closely related ATPases. We have also found that the multiubiquitin chain binding protein Mcb1, a homolog of the mammalian S5a protein, is a subunit of the yeast proteasome. However, contrary to expectation, MCB1 is not an essential gene in yeast. The mcb1 mutant grows at a nearly wild-type rate, and the breakdown of most ubiquitin-protein conjugates is unaffected in this strain. One substrate, Ub-Proline-beta gal, was found to require MCB1 for its breakdown, but it remains unclear whether Mcb1 serves as a ubiquitin receptor in this process. Our data suggest that the recognition of ubiquitin conjugates by the proteasome is a complex process which must involve proteins other than Mcb1.
Mol Biol Rep 1997 Mar
PMID:ATPase and ubiquitin-binding proteins of the yeast proteasome. 922 76

Degradation of a protein via the ubiquitin proteolytic pathway involves two successive steps. Covalent attachment of ubiquitin to the target protein and degradation of the tagged substrate by the 26S proteasome. Most native cellular proteins that are targeted by the ubiquitin system are short-lived transcriptional activators and growth and cell cycle regulators, as well as unstable membrane proteins. In the present study we demonstrate the involvement of the system in the degradation of tyrosine aminotransferase (TAT), a key enzyme in intermediary metabolism. In vitro, we have shown that the native enzyme is conjugated and degraded in a system that requires ATP and ubiquitin. Degradation was monitored by following the decrease of catalytic activity as well as disappearance of the protein molecule. The enzyme could be protected from degradation by association with its specific cofactor, pyridoxal phosphate (PLP). In vivo, we prepared cell extracts from livers of animals in which TAT was induced by starvation and corticosteroid administration. The dramatic increase in the level of the enzyme was accompanied by a concomitant increase in the level of specific TAT-ubiquitin adducts.
Mol Biol Rep 1997 Mar
PMID:Ubiquitin-mediated degradation of tyrosine aminotransferase (TAT) in vitro and in vivo. 922 77

There is extensive reprogramming of the ATPase regulators of the 26S proteasome before the programmed elimination of the abdominal intersegmental muscles (ISM) after eclosion in Manduca sexta [1]. This extensive ATPase reprogramming only occurs in ISM which are destined to die and not in flight muscle (FM). The MS73 ATPase also increases in the proleg retractor muscles which die at a developmentally different stage to ISM. The non-ATPase regulator S5a shows a similar increase to the ATPase regulators. We have cloned the Manduca SUG2 ATPase and shown that this ATPase is a component of the 26S proteasome. This ATPase shows a similar increase in concentration to the other ATPases in 26S proteasomes before muscle death. The SUG2 ATPase is also associated with other smaller complexes besides the 26S proteasome which act as activators of the 26S proteasome. Finally, in a yeast two-hybrid genetic screen we have identified a protein in human brain which interacts with the MS73 ATPase (and human S6). The interacting protein contains 6 ankyrin repeats and is co-immunoprecipitated with anti-MS73 antiserum after in vitro transcription/translation. The ankyrin repeat protein may interact with the MS73 ATPase as part of the substrate recognition process by the 26S proteasome. Many proteins degraded by the 26S proteasome contain ankyrin repeats, e.g. IkB and some cyclins: binding through ankyrin repeats to an ATPase regulator may complement protein ubiquitination and S5a binding as recognition signals by the 26S proteasome.
Mol Biol Rep 1997 Mar
PMID:The 26S-proteasome: regulation and substrate recognition. 922 79

Increases of oxidatively modified protein in the cell have been associated with the aging process. Such an accumulation of damaged protein may be the result of increase in the rate of protein oxidation and/or decrease in the rate of degradation of oxidized protein. The multicatalytic proteinase or proteasome is known to be the major proteolytic system involved in the removal of oxidized protein. We have reported that, after isolation of the 20S proteasome from the liver of young and old male Fischer 344 rat, out of the three peptidase activities (chymotrypsin-like, trypsin-like and peptidyl-glutamyl peptide hydrolase) we assayed with fluorogenic peptides, the peptidyl-glutamyl peptide hydrolase activity was declining with age to a value approximately 50% of that observed for protease purified from young rats. The proteasome was subjected to metal catalyzed oxidation to determine the susceptibility of the different peptidase activities to oxidative inactivation. Both trypsin-like and peptidyl-glutamyl peptide hydrolase activities were found sensitive to oxidation. Treatment of the proteasome with 4-hydroxy-2-nonenal, a major lipid peroxidation product, was also found to inactivate the trypsin-like activity. However, the trypsin-like activity was protected from inactivation by metal catalyzed oxidation in proteasome preparations contaminated with HSP 90, a protein that often copurifies with the proteasome. Upon addition of HSP 90 to pure 20S active proteasome, the trypsin-like activity was protected from inactivation by metal catalyzed oxidation and from inactivation by treatment with 4-hydroxy-2-nonenal. These results suggest a possible intervention of HSP 90 in response to oxidative stress in preventing the inactivation of the proteasome by oxidative damage.
Mol Biol Rep 1997 Mar
PMID:Proteasome inactivation upon aging and on oxidation-effect of HSP 90. 922 80

c-fos and c-jun proto-oncogenes have originally been found in mutated forms in murine and avian oncogenic retroviruses. They both define multigenic families of transcription factors. Both c-jun and c-fos proteins are metabolically unstable. In vivo and in vitro work by various groups suggests that multiple proteolytic machineries, including the lysosomes, the proteasome and the ubiquitous calpains, may participate in the destruction of c-fos and c-jun. The relative contribution of each pathway is far from being known and it cannot be excluded that it varies according to the cell context and/or the physiological conditions. It has been demonstrated that, in certain occurrences, the degradation of both c-fos and c-jun by the proteasome in vivo involves the ubiquitin pathway. However, the possibility that proteasomal degradation can also occur in a manner independent of the E1 enzyme of the ubiquitin cycle remains an open issue.
Mol Biol Rep 1997 Mar
PMID:Complex mechanisms for c-fos and c-jun degradation. 922 81


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