Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Livers of Wistar rats were stored between 0 and 36 hrs. in the University of Wisconsin preservation liquid in order to determine time-related biochemical and morphological hepatic changes. Ursodeoxycholate (100 microM) was also added in the medium to test the hepatoprotective properties of the bile salt. Biochemical assays were performed on hepatic microsomes, plasma and biliary canalicular membranes. Protein and lipid composition of the microsomal and baso-lateral plasma membranes remained stable. Protein and cholesterol content of the biliary canalicular membranes decreased, phospholipid/cholesterol ratio increased between 0 and 36 hrs.; it resulted in a leak of 5'-nucleotidase and leucine amino peptidase activity of these biliary canalicular membranes, especially up to 12 hrs. Between 0 and 36 hrs., the lipid and protein content remained stable in the plasma membranes, as well as both tested enzymatic activities. Observations under electron microscopy showed alterations and underlined fragility of the bile canaliculi, particularly after 24 hrs. preservation. Ultrastructure of sinusoidal membranes showed damaged microvilli. Endoplasmic reticulum remained unchanged, in relation to the stability of the microsomal lipidic, proteic content and hydroxymethylglutaryl-coenzyme A reductase activity, except the decreased protein content after preservation for 36 hrs without ursodeoxycholate. Ursodeoxycholate by itself did not protect against the described disturbances.
Cell Mol Biol (Noisy-le-grand) 1996 Jun
PMID:Time-related changes of cold-stored rat liver in University of Wisconsin solution. Effect of ursodeoxycholate. 882 4

The utilization of exogenous peptides was studied in mutants of Lactococcus lactis in which combinations of the peptidase genes pepN, pepC, pepO, pepX and pepT were deleted. Multiple mutants lacking PepN, PepC, PepT plus PepX could not grow on peptides such as Leu-Gly-Gly, Gly-Phe-Leu, Leu-Gly-Pro, Ala-Pro-Leu and Gly-Leu-Gly-Leu, respectively, indicating that no other peptidases are present to release the essential amino acid Leu. In these mutants, peptides accumulate intracellularly, demonstrating that peptides are translocated as whole entities prior to degradation. The mutant lacking all five peptidases could still grow on Gly-Leu and Tyr-Gly-Gly-Phe-Leu, which confirmed the presence of a dipeptidase and led to the identification of an unknown PepO-like endopeptidase. These studies have also shown that the general aminopeptidases PepN, PepC and PepT have overlapping but not identical specificities and differ in their overall activity towards individual peptides. In contrast, PepX has an unique specificity, because it is the only enzyme which can efficiently degrade Ala-Pro-Leu. The concerted action of peptidases in the breakdown of particular peptides revealed how these substrates are utilized as sources of nitrogen.
Mol Microbiol 1996 Jul
PMID:Fate of peptides in peptidase mutants of Lactococcus lactis. 884 39

IMP1 encodes a subunit of the mitochondrial inner membrane peptidase responsible for the proteolytic processing of cytochrome oxidase subunit 2 (Cox2) and cytochrome b2 (Cytb2). The molecular defect in an imp1 mutation and the characterisation of a high-copy-number suppressor is described. A deletion of the suppressor region causes respiration deficiency. The DNA sequence revealed three very small overlapping ORFs. Constructs which carried termination codons within the ORFs or lacked ATG initiation codons still retained complementing activity on a high-copy-number plasmid. Nevertheless, the possibility that the suppressor acts at DNA or RNA level could be excluded. Subcloning of the ORFs, complementation analysis in low-copy-number plasmids and transcript mapping identified the 222 bp ORF as the suppressor gene designated SOM1. The SOM1 gene is transcribed into a 375 bp polyadenylated RNA and the deduced amino acid sequence predicts a small protein of 8.4 kDa with no significant sequence similarity to known proteins. In the som1 deletion mutant, proteolytic processing of the Cox2 precursor is prevented and Cytb2 is strongly reduced. SOM1 represents a new small gene which encodes a novel factor that is essential for the correct function of the Imp1 peptidase and/or the protein sorting machinery.
Mol Gen Genet 1996 Sep 25
PMID:SOM 1, a small new gene required for mitochondrial inner membrane peptidase function in Saccharomyces cerevisiae. 887 45

Microcin B17 (MccB17) is a ribosomally encoded DNA-gyrase inhibitor. Ribosomally encoded antibiotics are derived from precursors containing an N-terminal leader, which is removed during maturation, and a C-terminal structural peptide. PreMccB17, the translational product of mcbA, is modified into proMccB17 by the action of three enzymes, McbB, McbC, and McbD. A chromosomally encoded peptidase then converts proMccB17 into MccB17. The role of McbB, McbC, and McbD is to convert glycine, cysteine, and serine residues present in preMccB17 into four thiazole and four oxazole rings. Using a modification-specific antibody rather than antimicrobial activity, we show that the 26-amino-acid N-terminal leader of preMccB17 is essential for the conversion of preMccB17 into proMccB17. Neither a preMccB17 peptide lacking the leader nor a preMccB17-beta-galactosidase fusion lacking the leader are post-translationally modified.
Mol Microbiol 1997 Jan
PMID:The leader peptide is essential for the post-translational modification of the DNA-gyrase inhibitor microcin B17. 900 29

Aminopeptidase-degradable leucine enkephalin (LE) was coupled with disaccharide (cellobiose or gentiobiose). Acetic acid writhing assay (for peripheral effect) showed that cellobiose-coupled LE (CcpLE) as well as LE had analgesic activity by subcutaneous (s.c.) administration to mice pretreated (s.c. administration) with peptidase inhibitors, whereas any analgesic effect was not observed after s.c. administration of CcpLE or LE without peptidase inhibitors. However, gentiobiose-coupled LE (EcpLE) did not have analgesic activity even with pretreatment of peptidase inhibitors. On the other hand, hot-plate assay (for central effect) did not indicate obvious analgesic effect after s.c. administration of CcpLE or EcpLE with pretreatment of peptidase inhibitors. Significant difference of stability against peptidase was not observed between CcpLE and EcpLE. Therefore, it was concluded that CcpLE is a peripherally active analgesic.
Res Commun Mol Pathol Pharmacol 1997 Jan
PMID:Peripherally active analgesia of aminopeptidase-resistant sugar-coupled leucine enkephalin. 905 51

Recently, we have reported the isolation and purification of 20S proteasomes from both the procyclic and bloodstream forms of Trypanosoma brucei, but no 26S proteasome was identified under those experimental conditions (Hua et al., Mol. Biochem. Parasitol. (1996) 78, 33-46). Subsequent attempts to identify a 26S proteasome in T. brucei led to the discovery of another form of the 20S proteasome designated the activated 20S proteasome because it exhibited much higher peptidase activities than the original 20S proteasome on all the fluorogenic peptides tested, and it crossreacted with the rabbit antisera against the 20S proteasomes purified from T. brucei. The activated 20S proteasome can be isolated from both procyclic and bloodstream forms of T. brucei and has a slightly higher molecular weight than the 20S proteasome. It is stable in the absence of ATP but susceptible to elution through a DE52 column. Analysis of the activated 20S proteasome in SDS-PAGE showed the presence of all the subunit proteins from the 20S proteasome plus an extra protein with an estimated molecular mass of 26 kDa. This protein, designated PA26, is not a degradation product of the 20S proteasomal subunit proteins. It could be a homolog of the bovine PA28 and human 11S regulator protein which form complexes with the 20S proteasomes resulting in activation of their peptidase activities. This likelihood was confirmed in a reconstitution experiment in which PA26 separated from the proteasome by a DE52 column chromatography was re-introduced into the purified 20S proteasome, and resulted in the emergence of a new protein band with the same mobility and peptidase activities as the activated 20S proteasome in native polyacrylamide gel electrophoresis. The presence of an activated 20S proteasome rather than a homolog of the 26S proteasome in T. brucei suggests that PA26 may play an important role in regulating the proteasome-mediated protein degradations in trypanosomes.
 ...
PMID:Identification and characterization of an activated 20S proteasome in Trypanosoma brucei. 911 74

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

The proteasome activator PA28 or 11S regulator is a protein complex composed of two different but homologous polypeptides, termed PA28alpha and PA28beta. The purified activator protein (approximately 200 kDa) is a ring-shaped heteromultimer containing the two polypeptides, possibly with an (alpha3beta3 stoichiometry. The activator, which by itself shows no hydrolytic activity elicits activation of the proteasome's multiple peptidase activities by binding to the terminal rings of the proteinase. In vitro, active PA28 can be reconstituted from isolated alpha and beta subunits, yielding two different oligomers: with the single alpha subunit, PA28alpha homomultimers with moderate stimulatory activity toward 20S proteasomes are obtained whereas isolated beta-subunits are unable to form oligomers and are devoid of stimulatory activity. However, in the presence of both subunits, alphabeta heteromultimers form, concomitant with restoration of full stimulatory activity. The recent finding that PA28 modulates the proteasome-catalyzed production of antigenic peptides presented to the immune system on MHC class I molecules indicates a cellular function of the activator in antigen processing.
Mol Biol Rep 1997 Mar
PMID:Structural and functional properties of proteasome activator PA28. 922 87

A precise knowledge of the role of subunits of the 19S complex and the PA28 regulator, which associate with the 20S proteasome and regulate its peptidase activities, may contribute to design new therapeutic approaches for preventing muscle wasting in human diseases. The proteasome is mainly responsible for the muscle wasting of tumor-bearing and unweighted rats. The expression of some ATPase (MSS1, P45) and non ATPase (P112-L, P31) subunits of the 19S complex, and of the two subunits of the PA28 regulator, was studied in such atrophying muscles. The mRNA levels for all studied subunits increased in unweighted rats, and analysis of MSS1 mRNA distribution profile in polyribosomes showed that this subunit entered active translation. By contrast, only the mRNA levels for MSS1 increased in the muscles from cancer rats. Thus, gene expression of the proteasome regulatory subunits depends on a given catabolic state. Torbafylline, a xanthine derivative which inhibits tumor necrosis factor production, prevented the activation of protein breakdown and the increased expression of 20S proteasome subunits in cancer rats, without reducing the elevated MSS1 mRNA levels. Thus, the increased expression of MSS1 is regulated independently of 20S proteasome subunits, and did not result in accelerated proteolysis.
Mol Biol Rep 1997 Mar
PMID:Expression of subunits of the 19S complex and of the PA28 activator in rat skeletal muscle. 922 88

Control and targeting of the proteolytic activity of the major intracellular protease, the proteasome, is accomplished by various regulatory protein complexes that may form higher-order assemblies with the proteasome. An activator of proteolytic activity, PA700, has been shown to have an ATP-dependent stimulatory effect on the peptidase activities of the proteasome, and another protein factor, the modulator, further enhances the effect of PA700. Here we show that the addition of PA700 endows the proteasome with the ability to cleave ubiquitinated proteins, a property associated with the previously isolated 26 S form of the proteasome. The modulator further stimulates this specific activity, without having any such effect on the proteasome alone. Using electron microscopy, we show that addition of PA700 causes the appearance of protein "caps" at one or both ends of proteasomes, forming structures that are indistinguishable from 26 S proteasomes. Quantitation of the numbers of uncapped, singly capped and doubly capped complexes indicates cooperativity in the association of PA700 with the two ends of the proteasome. Addition of modulator protein makes no further structural modification that is detectable by electron microscopy, but does cause an increase in the number of capped complexes visible at subsaturating concentrations of PA700. Hence PA700 converts the proteasome both functionally and structurally to the 26 S form, and the modulator promotes this transformation, apparently without stable association with the resulting complex.
J Mol Biol 1997 Oct 31
PMID:Structural and functional effects of PA700 and modulator protein on proteasomes. 935 53


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>