AnatomyOrganismsDiseasesChemicals and DrugsAnalytical, Diagnostic and Therapeutic Techniques and EquipmentPhenomena and ProcessesInformation Science
Proteasome Endopeptidase ComplexProteasome InhibitorsEndopeptidasesNeprilysinCysteine EndopeptidasesSerine EndopeptidasesThiorphanProtease InhibitorsMultienzyme ComplexesLeupeptinsPHEX Phosphate Regulating Neutral EndopeptidaseBoronic AcidsCysteine Proteinase InhibitorsPyrazinesMetalloendopeptidasesAmino Acid SequenceMolecular Sequence DataSubstrate SpecificityUbiquitinsPeptide HydrolasesOligopeptidesGlycopeptidesHydrolysisSerine Proteinase InhibitorsNeurotensinLysostaphinProteolysisAspartic Acid EndopeptidasesAcetylcysteineDipeptidesUbiquitinationProtein Processing, Post-TranslationalKineticsAtrial Natriuretic FactorPeptidesPolyubiquitinThiazepinesCell LinePeptide FragmentsCathepsin BCarboxypeptidasesAminopeptidasesChromatography, High Pressure LiquidChymotrypsinBase SequenceUbiquitin-Protein LigasesUbiquitinated ProteinsRecombinant ProteinsProtein SubunitsSequence Homology, Amino AcidSubstance PElectrophoresis, Polyacrylamide GelExopeptidasesApoptosisProtein BindingEnkephalin, LeucineProteinsBlotting, WesternBradykininHypophosphatemiaBotulinum Toxins, Type ACell Line, TumorIndansFlavobacteriumCloning, MolecularBinding SitesThermoplasmaMutationCarboxypeptidases AThermolysinProtein Structure, TertiaryATP-Dependent EndopeptidasesPeptidoglycanProtein PrecursorsEnzyme InhibitorsEnzyme ActivationCells, CulturedKidneyDipeptidyl-Peptidases and Tripeptidyl-PeptidasesPropionatesSaccharomyces cerevisiae ProteinsSaccharomyces cerevisiaeMolecular WeightRNA, MessengerEnzyme StabilityDiazomethaneTransfectionHydrogen-Ion ConcentrationFamilial Hypophosphatemic RicketsAdenosine TriphosphatasesSequence AlignmentLactonesAngiotensin-Converting Enzyme InhibitorsImmunoblotting
Proteasome Endopeptidase Complex
A large multisubunit complex that plays an important role in the degradation of most of the cytosolic and nuclear proteins in eukaryotic cells. It contains a 700-kDa catalytic sub-complex and two 700-kDa regulatory sub-complexes. The complex digests ubiquitinated proteins and protein activated via ornithine decarboxylase antizyme.
Proteasome Inhibitors
Compounds that inhibit the function or proteolytic action of the PROTEASOME.
Endopeptidases
A subclass of PEPTIDE HYDROLASES that catalyze the internal cleavage of PEPTIDES or PROTEINS.
Neprilysin
Enzyme that is a major constituent of kidney brush-border membranes and is also present to a lesser degree in the brain and other tissues. It preferentially catalyzes cleavage at the amino group of hydrophobic residues of the B-chain of insulin as well as opioid peptides and other biologically active peptides. The enzyme is inhibited primarily by EDTA, phosphoramidon, and thiorphan and is reactivated by zinc. Neprilysin is identical to common acute lymphoblastic leukemia antigen (CALLA Antigen), an important marker in the diagnosis of human acute lymphocytic leukemia. There is no relationship with CALLA PLANT.
Cysteine Endopeptidases
ENDOPEPTIDASES which have a cysteine involved in the catalytic process. This group of enzymes is inactivated by CYSTEINE PROTEINASE INHIBITORS such as CYSTATINS and SULFHYDRYL REAGENTS.
Serine Endopeptidases
Any member of the group of ENDOPEPTIDASES containing at the active site a serine residue involved in catalysis.
Thiorphan
A potent inhibitor of membrane metalloendopeptidase (ENKEPHALINASE). Thiorphan potentiates morphine-induced ANALGESIA and attenuates naloxone-precipitated withdrawal symptoms.
Protease Inhibitors
Compounds which inhibit or antagonize biosynthesis or actions of proteases (ENDOPEPTIDASES).
Multienzyme Complexes
Systems of enzymes which function sequentially by catalyzing consecutive reactions linked by common metabolic intermediates. They may involve simply a transfer of water molecules or hydrogen atoms and may be associated with large supramolecular structures such as MITOCHONDRIA or RIBOSOMES.
Leupeptins
A group of acylated oligopeptides produced by Actinomycetes that function as protease inhibitors. They have been known to inhibit to varying degrees trypsin, plasmin, KALLIKREINS, papain and the cathepsins.
PHEX Phosphate Regulating Neutral Endopeptidase
A membrane-bound metalloendopeptidase that may play a role in the degradation or activation of a variety of PEPTIDE HORMONES and INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS. Genetic mutations that result in loss of function of this protein are a cause of HYPOPHOSPHATEMIC RICKETS, X-LINKED DOMINANT.
Boronic Acids
Inorganic or organic compounds that contain the basic structure RB(OH)2.
Cysteine Proteinase Inhibitors
Exogenous and endogenous compounds which inhibit CYSTEINE ENDOPEPTIDASES.
Pyrazines
Metalloendopeptidases
ENDOPEPTIDASES which use a metal such as ZINC in the catalytic mechanism.
Amino Acid Sequence
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
Molecular Sequence Data
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Substrate Specificity
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
Ubiquitins
A family of proteins that are structurally-related to Ubiquitin. Ubiquitins and ubiquitin-like proteins participate in diverse cellular functions, such as protein degradation and HEAT-SHOCK RESPONSE, by conjugation to other proteins.
Peptide Hydrolases
Hydrolases that specifically cleave the peptide bonds found in PROTEINS and PEPTIDES. Examples of sub-subclasses for this group include EXOPEPTIDASES and ENDOPEPTIDASES.
Oligopeptides
Peptides composed of between two and twelve amino acids.
Glycopeptides
Proteins which contain carbohydrate groups attached covalently to the polypeptide chain. The protein moiety is the predominant group with the carbohydrate making up only a small percentage of the total weight.
Hydrolysis
The process of cleaving a chemical compound by the addition of a molecule of water.
Serine Proteinase Inhibitors
Exogenous or endogenous compounds which inhibit SERINE ENDOPEPTIDASES.
Neurotensin
A biologically active tridecapeptide isolated from the hypothalamus. It has been shown to induce hypotension in the rat, to stimulate contraction of guinea pig ileum and rat uterus, and to cause relaxation of rat duodenum. There is also evidence that it acts as both a peripheral and a central nervous system neurotransmitter.
Lysostaphin
A 25-kDa peptidase produced by Staphylococcus simulans which cleaves a glycine-glcyine bond unique to an inter-peptide cross-bridge of the STAPHYLOCOCCUS AUREUS cell wall. EC 3.4.24.75.
Proteolysis
Cleavage of proteins into smaller peptides or amino acids either by PROTEASES or non-enzymatically (e.g., Hydrolysis). It does not include Protein Processing, Post-Translational.
Aspartic Acid Endopeptidases
A sub-subclass of endopeptidases that depend on an ASPARTIC ACID residue for their activity.
Acetylcysteine
The N-acetyl derivative of CYSTEINE. It is used as a mucolytic agent to reduce the viscosity of mucous secretions. It has also been shown to have antiviral effects in patients with HIV due to inhibition of viral stimulation by reactive oxygen intermediates.
Dipeptides
Peptides composed of two amino acid units.
Ubiquitination
The act of ligating UBIQUITINS to PROTEINS to form ubiquitin-protein ligase complexes to label proteins for transport to the PROTEASOME ENDOPEPTIDASE COMPLEX where proteolysis occurs.
Protein Processing, Post-Translational
Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.
Kinetics
The rate dynamics in chemical or physical systems.
Atrial Natriuretic Factor
A potent natriuretic and vasodilatory peptide or mixture of different-sized low molecular weight PEPTIDES derived from a common precursor and secreted mainly by the HEART ATRIUM. All these peptides share a sequence of about 20 AMINO ACIDS.
Peptides
Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.
Polyubiquitin
An oligomer formed from the repetitive linking of the C-terminal glycine of one UBIQUITIN molecule via an isopeptide bond to a lysine residue on a second ubiquitin molecule. It is structurally distinct from UBIQUITIN C, which is a single protein containing a tandemly arrayed ubiquitin peptide sequence.
Thiazepines
Cell Line
Established cell cultures that have the potential to propagate indefinitely.
Peptide Fragments
Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.
Cathepsin B
A lysosomal cysteine proteinase with a specificity similar to that of PAPAIN. The enzyme is present in a variety of tissues and is important in many physiological and pathological processes. In pathology, cathepsin B has been found to be involved in DEMYELINATION; EMPHYSEMA; RHEUMATOID ARTHRITIS, and NEOPLASM INVASIVENESS.
Carboxypeptidases
Enzymes that act at a free C-terminus of a polypeptide to liberate a single amino acid residue.
Aminopeptidases
A subclass of EXOPEPTIDASES that act on the free N terminus end of a polypeptide liberating a single amino acid residue. EC 3.4.11.
Chromatography, High Pressure Liquid
Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.
Chymotrypsin
A serine endopeptidase secreted by the pancreas as its zymogen, CHYMOTRYPSINOGEN and carried in the pancreatic juice to the duodenum where it is activated by TRYPSIN. It selectively cleaves aromatic amino acids on the carboxyl side.
Base Sequence
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
Ubiquitin-Protein Ligases
A diverse class of enzymes that interact with UBIQUITIN-CONJUGATING ENZYMES and ubiquitination-specific protein substrates. Each member of this enzyme group has its own distinct specificity for a substrate and ubiquitin-conjugating enzyme. Ubiquitin-protein ligases exist as both monomeric proteins multiprotein complexes.
Ubiquitinated Proteins
Proteins covalently modified with UBIQUITINS or UBIQUITIN-LIKE PROTEINS.
Recombinant Proteins
Proteins prepared by recombinant DNA technology.
Protein Subunits
Single chains of amino acids that are the units of multimeric PROTEINS. Multimeric proteins can be composed of identical or non-identical subunits. One or more monomeric subunits may compose a protomer which itself is a subunit structure of a larger assembly.
Sequence Homology, Amino Acid
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
Substance P
An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of PAIN, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses.
Electrophoresis, Polyacrylamide Gel
Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.
Exopeptidases
A sub-class of PEPTIDE HYDROLASES that act only near the ends of polypeptide chains.
Apoptosis
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
Protein Binding
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
Enkephalin, Leucine
One of the endogenous pentapeptides with morphine-like activity. It differs from MET-ENKEPHALIN in the LEUCINE at position 5. Its first four amino acid sequence is identical to the tetrapeptide sequence at the N-terminal of BETA-ENDORPHIN.
Proteins
Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.
Blotting, Western
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
Bradykinin
A nonapeptide messenger that is enzymatically produced from KALLIDIN in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from MAST CELLS during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter.
Hypophosphatemia
A condition of an abnormally low level of PHOSPHATES in the blood.
Botulinum Toxins, Type A
A serotype of botulinum toxins that has specificity for cleavage of SYNAPTOSOMAL-ASSOCIATED PROTEIN 25.
Cell Line, Tumor
A cell line derived from cultured tumor cells.
Indans
Aryl CYCLOPENTANES that are a reduced (protonated) form of INDENES.
Flavobacterium
A genus of gram-negative, aerobic, rod-shaped bacteria widely distributed in SOIL and WATER. Its organisms are also found in raw meats, MILK and other FOOD, hospital environments, and human clinical specimens. Some species are pathogenic in humans.
Cloning, Molecular
The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.
Binding Sites
The parts of a macromolecule that directly participate in its specific combination with another molecule.
Thermoplasma
A genus of facultatively anaerobic heterotrophic archaea, in the order THERMOPLASMALES, isolated from self-heating coal refuse piles and acid hot springs. They are thermophilic and can grow both with and without sulfur.
Mutation
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
Carboxypeptidases A
Carboxypeptidases that are primarily found the DIGESTIVE SYSTEM that catalyze the release of C-terminal amino acids. Carboxypeptidases A have little or no activity for hydrolysis of C-terminal ASPARTIC ACID; GLUTAMIC ACID; ARGININE; LYSINE; or PROLINE. This enzyme requires ZINC as a cofactor and was formerly listed as EC 3.4.2.1 and EC 3.4.12.2.
Thermolysin
A thermostable extracellular metalloendopeptidase containing four calcium ions. (Enzyme Nomenclature, 1992) 3.4.24.27.
Protein Structure, Tertiary
The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.
ATP-Dependent Endopeptidases
Endoproteases that contain proteolytic core domains and ATPase-containing regulatory domains.
Peptidoglycan
Protein Precursors
Enzyme Inhibitors
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
Enzyme Activation
Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.
Cells, Cultured
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
Kidney
Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.
Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
A subclass of exopeptidases that includes enzymes which cleave either two or three AMINO ACIDS from the end of a peptide chain.
Propionates
Derivatives of propionic acid. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the carboxyethane structure.
Saccharomyces cerevisiae Proteins
Proteins obtained from the species SACCHAROMYCES CEREVISIAE. The function of specific proteins from this organism are the subject of intense scientific interest and have been used to derive basic understanding of the functioning similar proteins in higher eukaryotes.
Saccharomyces cerevisiae
A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement.
Molecular Weight
The sum of the weight of all the atoms in a molecule.
RNA, Messenger
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
Enzyme Stability
The extent to which an enzyme retains its structural conformation or its activity when subjected to storage, isolation, and purification or various other physical or chemical manipulations, including proteolytic enzymes and heat.
Diazomethane
Transfection
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
Hydrogen-Ion Concentration
The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH = log 1/2[1/(H+)], where (H+) is the hydrogen ion concentration in gram equivalents per liter of solution. (McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)
Familial Hypophosphatemic Rickets
A hereditary disorder characterized by HYPOPHOSPHATEMIA; RICKETS; OSTEOMALACIA; renal defects in phosphate reabsorption and vitamin D metabolism; and growth retardation. Autosomal and X-linked dominant and recessive variants have been reported.
Adenosine Triphosphatases
A group of enzymes which catalyze the hydrolysis of ATP. The hydrolysis reaction is usually coupled with another function such as transporting Ca(2+) across a membrane. These enzymes may be dependent on Ca(2+), Mg(2+), anions, H+, or DNA.
Sequence Alignment
The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.
Lactones
Cyclic esters of hydroxy carboxylic acids, containing a 1-oxacycloalkan-2-one structure. Large cyclic lactones of over a dozen atoms are MACROLIDES.
Angiotensin-Converting Enzyme Inhibitors
A class of drugs whose main indications are the treatment of hypertension and heart failure. They exert their hemodynamic effect mainly by inhibiting the renin-angiotensin system. They also modulate sympathetic nervous system activity and increase prostaglandin synthesis. They cause mainly vasodilation and mild natriuresis without affecting heart rate and contractility.
Immunoblotting
Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.

Re-entering the translocon from the lumenal side of the endoplasmic reticulum. Studies on mutated carboxypeptidase yscY species. (1/7628)

Misfolded or unassembled secretory proteins are retained in the endoplasmic reticulum (ER) and subsequently degraded by the cytosolic ubiquitin-proteasome system. This requires their retrograde transport from the ER lumen into the cytosol, which is mediated by the Sec61 translocon. It had remained a mystery whether ER-localised soluble proteins are at all capable of re-entering the Sec61 channel de novo or whether a permanent contact of the imported protein with the translocon is a prerequisite for retrograde transport. In this study we analysed two new variants of the mutated yeast carboxypeptidase yscY, CPY*: a carboxy-terminal fusion protein of CPY* and pig liver esterase and a CPY* species carrying an additional glycosylation site at its carboxy-terminus. With these constructs it can be demonstrated that the newly synthesised CPY* chain is not retained in the translocation channel but reaches its ER lumenal side completely. Our data indicate that the Sec61 channel provides the essential pore for protein transport through the ER membrane in either direction; persistent contact with the translocon after import seems not to be required for retrograde transport.  (+info)

Oligosaccharide modification in the early secretory pathway directs the selection of a misfolded glycoprotein for degradation by the proteasome. (2/7628)

The role of conformation-based quality control in the early secretory pathway is to eliminate misfolded polypeptides and unassembled multimeric protein complexes from the endoplasmic reticulum, ensuring the deployment of only functional molecules to distal sites. The intracellular fate of terminally misfolded human alpha1-antitrypsin was examined in hepatoma cells to identify the functional role of asparagine-linked oligosaccharide modification in the selection of glycoproteins for degradation by the cytosolic proteasome. Proteasomal degradation required physical interaction with the molecular chaperone calnexin. Altered sedimentation of intracellular complexes following treatment with the specific proteasome inhibitor lactacystin, and in combination with mannosidase inhibition, revealed that the removal of mannose from attached oligosaccharides abrogates the release of misfolded alpha1-antitrypsin from calnexin prior to proteasomal degradation. Intracellular turnover was arrested with kifunensine, implicating the participation of endoplasmic reticulum mannosidase I in the disposal process. Accelerated degradation occurred in a mannosidase-independent manner and was arrested by lactacystin, in response to the posttranslational inhibition of glucosidase II, demonstrating that the attenuated removal of glucose from attached oligosaccharides functions as the underlying rate-limiting step in the proteasome-mediated pathway. A model is proposed in which the removal of mannose from multiple attached oligosaccharides directs calnexin in the selection of misfolded alpha1-antitrypsin for degradation by the proteasome.  (+info)

Possible involvement of proteasomes (prosomes) in AUUUA-mediated mRNA decay. (3/7628)

We have identified a cellular target for proteasomal endonuclease activity. Thus, 20 S proteasomes interact with the 3'-untranslated region of certain cytoplasmic mRNAs in vivo, and 20 S proteasomes isolated from Friend leukemia virus-infected mouse spleen cells were found to be associated with a mRNA fragment showing great homology to the 3'-untranslated region of tumor necrosis factor-beta mRNA that contains AUUUA sequences. We furthermore demonstrate that 20 S proteasomes destabilize oligoribonucleotides corresponding to the 3'-untranslated region of tumor necrosis factor-alpha, creating a specific cleavage pattern. The cleavage reaction is accelerated with increasing number of AUUUA motifs, and major cleavage sites are localized at the 5' side of the A residues. These results strongly suggest that 20 S proteasomes could be involved in the destabilization of cytokine mRNAs such as tumor necrosis factor mRNAs and other short-lived mRNAs containing AUUUA sequences.  (+info)

Mechanisms for generating the autonomous cAMP-dependent protein kinase required for long-term facilitation in Aplysia. (4/7628)

The formation of a persistently active cAMP-dependent protein kinase (PKA) is critical for establishing long-term synaptic facilitation (LTF) in Aplysia. The injection of bovine catalytic (C) subunits into sensory neurons is sufficient to produce protein synthesis-dependent LTF. Early in the LTF induced by serotonin (5-HT), an autonomous PKA is generated through the ubiquitin-proteasome-mediated proteolysis of regulatory (R) subunits. The degradation of R occurs during an early time window and appears to be a key function of proteasomes in LTF. Lactacystin, a specific proteasome inhibitor, blocks the facilitation induced by 5-HT, and this block is rescued by injecting C subunits. R is degraded through an allosteric mechanism requiring an elevation of cAMP coincident with the induction of a ubiquitin carboxy-terminal hydrolase.  (+info)

Constitutive degradation of PML/RARalpha through the proteasome pathway mediates retinoic acid resistance. (5/7628)

PML/RARalpha is the leukemogenetic protein of acute promyelocytic leukemia (APL). Treatment with retinoic acid (RA) induces degradation of PML/RARalpha, differentiation of leukaemic blasts, and disease remission. However, RA resistance arises during RA treatment of APL patients. To investigate the phenomenon of RA resistance in APL, we generated RA-resistant sublines from APL-derived NB4 cells. The NB4.007/6 RA-resistant subline does not express the PML/RARalpha protein, although its mRNA is detectable at levels comparable to those of the parental cell line. In vitro degradation assays showed that the half-life of PML/RARalpha is less than 30 minutes in NB4.007/6 and longer than 3 hours in NB4. Treatment of NB4.007/6 cells with the proteasome inhibitors LLnL and lactacystin partially restored PML/RARalpha protein expression and resulted in a partial release of the RA-resistant phenotype. Similarly, forced expression of PML/RARalpha, but not RARalpha, into the NB4/007.6 cells restored sensitivity to RA treatment to levels comparable to those of the NB4 cells. These results indicate that constitutive degradation of PML/RARalpha protein may lead to RA resistance and that PML/RARalpha expression is crucial to convey RA sensitivity to APL cells.  (+info)

Regulation of the hypoxia-inducible transcription factor 1alpha by the ubiquitin-proteasome pathway. (6/7628)

HIF-1alpha (hypoxia-inducible factor 1alpha) is a basic-helix-loop-helix PAS (Per/Arnt/Sim) transcription factor that, under hypoxic conditions, dimerizes with a partner factor, the basic-helix-loop-helix/PAS protein Arnt, to recognize hypoxia-responsive elements of target genes. It has recently been demonstrated that HIF-1alpha protein but not mRNA levels are dramatically up-regulated in response to hypoxia. Here we show that inhibitors of 26 S proteasome activity produced a dramatic accumulation of endogenous as well as transfected HIF-1alpha protein under normoxic conditions, whereas the levels of Arnt protein were not affected. HIF-1alpha was polyubiquitinated in vivo under normoxic conditions, indicating rapid degradation via the ubiquitin-proteasome pathway. This degradation process appeared to target a region within the C terminus of HIF-1alpha. Importantly, HIF-1alpha ubiquitination was drastically decreased under hypoxic conditions. Up-regulation of HIF-1alpha protein by proteasome inhibitors did not result in transcriptional activation of reporter genes, indicating either the requirement of additional regulatory steps to induce functional activity of HIF-1alpha or the inability of polyubiquitinated forms of HIF-1alpha to mediate hypoxic signal transduction. In support of both these notions, we demonstrate that HIF-1alpha showed hypoxia-dependent translocation from the cytoplasm to the nucleus and that this regulatory mechanism was severely impaired in the presence of proteasome inhibitors. Taken together, these data demonstrate that the mechanism of hypoxia-dependent activation of HIF-1alpha is a complex multistep process and that stabilization of HIF-1alpha protein levels is not sufficient to generate a functional form.  (+info)

Proteasome-dependent degradation of the human estrogen receptor. (7/7628)

In eukaryotic cells, the ubiquitin-proteasome pathway is the major mechanism for the targeted degradation of proteins with short half-lives. The covalent attachment of ubiquitin to lysine residues of targeted proteins is a signal for the recognition and rapid degradation by the proteasome, a large multi-subunit protease. In this report, we demonstrate that the human estrogen receptor (ER) protein is rapidly degraded in mammalian cells in an estradiol-dependent manner. The treatment of mammalian cells with the proteasome inhibitor MG132 inhibits activity of the proteasome and blocks ER degradation, suggesting that ER protein is turned over through the ubiquitin-proteasome pathway. In addition, we show that in vitro ER degradation depends on ubiquitin-activating E1 enzyme (UBA) and ubiquitin-conjugating E2 enzymes (UBCs), and the proteasome inhibitors MG132 and lactacystin block ER protein degradation in vitro. Furthermore, the UBA/UBCs and proteasome inhibitors promote the accumulation of higher molecular weight forms of ER. The UBA and UBCs, which promote ER degradation in vitro, have no significant effect on human progesterone receptor and human thyroid hormone receptor beta proteins.  (+info)

The conserved SOCS box motif in suppressors of cytokine signaling binds to elongins B and C and may couple bound proteins to proteasomal degradation. (8/7628)

The suppressors of cytokine signaling (SOCS) family of proteins act as intracellular inhibitors of several cytokine signal transduction pathways. Their expression is induced by cytokine activation of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway and they act as a negative feedback loop by subsequently inhibiting the JAK/STAT pathway either by direct interaction with activated JAKs or with the receptors. These interactions are mediated at least in part by the SH2 domain of SOCS proteins but these proteins also contain a highly conserved C-terminal homology domain termed the SOCS box. Here we show that the SOCS box mediates interactions with elongins B and C, which in turn may couple SOCS proteins and their substrates to the proteasomal protein degradation pathway. Analogous to the family of F-box-containing proteins, it appears that the SOCS proteins may act as adaptor molecules that target activated cell signaling proteins to the protein degradation pathway.  (+info)

Alterations in cytoskeletal proteins and microtubule stability following 26S proteasome dysfunction in mouse brain cortical...Alterations in cytoskeletal proteins and microtubule stability following 26S proteasome dysfunction in mouse brain cortical...
This thesis investigates the levels and localisation of cytoskeletal proteins in mouse cortical neurons following 26S proteasome dysfunction (Psmc1fl/fl;CaMKIIα-Cre). This study provides new insights into the role of the UPS in maintain cytoskeletal proteins that may be important in neurodegenerative disease. We found an early increase in neurofilaments following 26S proteasome dysfunction; before obvious changes in microtubule stability. An increased free/polymerised tubulin ratio was evident at later stages indicative of microtubule instability in Psmc1fl/fl;CaMKIIα-Cre mice. In addition, we found decreased levels of microtubule proteins, microtubule-associated proteins and detyrosinated-tubulin; with increased tyrosinated-tubulin following 26S proteasome dysfunction. These changes are contrary to decreased STMN expression observed in Psmc1fl/fl;CaMKIIα-Cre mice. We suggest that decreasing STMN may be part of a negative feedback loop to stabilize MT following 26S proteasome dysfunction. ...
http://eprints.nottingham.ac.uk/47188/
PSMD14 - WikipediaPSMD14 - Wikipedia
26S proteasome non-ATPase regulatory subunit 14, also known as 26S proteasome non-ATPase subunit Rpn11, is an enzyme that in humans is encoded by the PSMD14 gene. This protein is one of the 19 essential subunits of a complete assembled 19S proteasome complex. Nine subunits Rpn3, Rpn5, Rpn6, Rpn7, Rpn8, Rpn9, Rpn11, SEM1(Yeast analogue for human protein DSS1), and Rpn12 form the lid sub complex of 19S regulatory particle for proteasome complex. The gene PSMD14 encodes one of 26S proteasome non-ATPase subunit. The human gene PSMD14 has 12 Exons and locates at chromosome band 2q24.2. The human protein 26S proteasome non-ATPase regulatory subunit 14 is 34.6 kDa in size and composed of 310 amino acids. The calculated theoretical pI of this protein is 6.06. 26S proteasome complex is usually consisted of a 20S core particle (CP, or 20S proteasome) and one or two 19S regulatory particles (RP, or 19S proteasome) on either one side or both side of the barrel-shaped 20S. The CP and RPs pertain distinct ...
https://en.wikipedia.org/wiki/PSMD14
PSMD1 - WikipediaPSMD1 - Wikipedia
26S proteasome non-ATPase regulatory subunit 1, also as known as 26S Proteasome Regulatory Subunit Rpn2 (systematic nomenclature), is a protein that in humans is encoded by the PSMD1 gene. This protein is one of the 19 essential subunits that contributes to the complete assembly of 19S proteasome complex. The gene PSMD1 encodes the largest non-ATPase subunit of the 19S regulator base, which is responsible for substrate recognition and binding. The human PSMD1 gene has 25 exons and locates at chromosome band 2q37.1. The human protein 26S proteasome non-ATPase regulatory subunit 1 is 106 kDa in size and composed of 953 amino acids. The calculated theoretical pI of this protein is 5.25. An alternative splicing during gene expression generates an isoform of the protein in which the amino acid sequence from 797-827 is missing. 26S proteasome complex is usually consisted of a 20S core particle (CP, or 20S proteasome) and one or two 19S regulatory particles (RP, or 19S proteasome) on either one side or ...
https://en.wikipedia.org/wiki/PSMD1
Cytokinin Growth Responses in Arabidopsis Involve the 26S Proteasome Subunit RPN12 | Plant CellCytokinin Growth Responses in Arabidopsis Involve the 26S Proteasome Subunit RPN12 | Plant Cell
Recent studies have implicated the ubiquitin/26S proteasome proteolytic pathway in many environmental and developmental responses in higher plants (Callis and Vierstra, 2000). Here, we extend its importance to cytokinin regulation with the demonstration that an Arabidopsis mutation affecting the synthesis of the RPN12a subunit of the 26S proteasome alters development consistent with a reduction in cytokinin responses. Previous data implicated the ubiquitin/26S proteasome system in the response to hormones, auxins, jasmonate, and abscisic acid (Xie et al., 1998; Gray and Estelle, 2000; Lopez-Molina et al., 2001). Given the complexity of this pathway in plants (in Arabidopsis, it includes more than 1100 genes), it is likely that most if not all hormone responses in plants are regulated at some level by such proteolysis.. In agreement with data from other eukaryotes, RPN12a is a component of the Arabidopsis 26S proteasome. At present, its biochemical function is unknown. RPN12a does not have any ...
http://www.plantcell.org/content/14/1/17?ijkey=e78580606cbe4bae01afffca42b16c87bc5d3465&keytype2=tf_ipsecsha
26S proteasome non-ATPase regulatory subunit 526S proteasome non-ATPase regulatory subunit 5
The 26S proteasome is a multicatalytic proteinase complex with a highly ordered structure composed of 2 complexes, a 20S core and a 19S regulator. The 20S core is composed of 4 rings of 28 non-identical subunits; 2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta subunits. The 19S regulator is composed of a base, which contains 6 ATPase subunits and 2 non-ATPase subunits, and a lid, which contains up to 10 non-ATPase subunits. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. This gene encodes a non-ATPase subunit of the 19S regulator base that functions as a chaperone protein during 26S proteasome assembly. [provided by RefSeq, Jul 2012 ...
https://pharos.nih.gov/idg/targets/Q16401
Functional and biochemical characterization of the 20S proteasome in a yeast temperature-sensitive mutant, rpt6-1 | BMC...Functional and biochemical characterization of the 20S proteasome in a yeast temperature-sensitive mutant, rpt6-1 | BMC...
Rpt6-1 is a thermosensitive yeast mutant with a deletion of a gene encoding a regulatory subunit of the 26S proteasome, RPT6, which is able to grow at 25°C but not at 37°C. In this study, peptidase activities, activation profiles, and the subunit composition of the 20S proteasome purified from the rpt6-1 mutant was characterized. The 20S proteasome purified from rpt6-1 exhibited low levels of peptidase activities in the absence of activators, but nearly same activated activities in the presence of activators, suggesting a gating defect in the proteasome channel. Detailed analyses of the composition of the 20S proteasome through separation of all subunits by two-dimensional gel electrophoresis followed by identification of each subunit using MALDI-TOF-MS revealed that two subunits, α1 and α7, differed from those of wild-type cells in both electrophoretic mobility and pI values. The changes in these two α-subunits were apparent at the permissive temperature, but disappeared during stress response at
https://bmcbiochem.biomedcentral.com/articles/10.1186/1471-2091-9-20
Proteasome subunit beta type-9Proteasome subunit beta type-9
The proteasome is a multicatalytic proteinase complex with a highly ordered ring-shaped 20S core structure. The core structure is composed of 4 rings of 28 non-identical subunits; 2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta subunits. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. This gene encodes a member of the proteasome B-type family, also known as the T1B family, that is a 20S core beta subunit. This gene is located in the class II region of the MHC (major histocompatibility complex). Expression of this gene is induced by gamma interferon and this gene product replaces catalytic subunit 1 (proteasome beta 6 subunit) in the immunoproteasome. Proteolytic processing is required to generate a mature subunit. [provided by RefSeq, Mar ...
https://pharos.nih.gov/idg/targets/P28065
Frontiers | FoxO1 Is a Novel Regulator of 20S Proteasome Subunits Expression and Activity | Cell and Developmental BiologyFrontiers | FoxO1 Is a Novel Regulator of 20S Proteasome Subunits Expression and Activity | Cell and Developmental Biology
Proteostasis collapses during aging resulting, among other things, in the accumulation of damaged and aggregated proteins. The proteasome is the main cellular proteolytic system and plays a fundamental role in the maintenance of protein homeostasis. Our previous work has demonstrated that senescence and aging are related to a decline in proteasome content and activities, while its activation extends lifespan in vitro and in vivo in various species. However, the mechanisms underlying this age-related decline of proteasome function and the down-regulation in expression of its subunits remain largely unclear. Here, we demonstrate that the Forkhead box-O1 (FoxO1) transcription factor directly regulates the expression of a 20S proteasome catalytic subunit and, hence, proteasome activity. Specifically, we demonstrate that knockout of FoxO1, but not of FoxO3, in mice severely impairs proteasome activity in several tissues, while depletion of IRS1 enhances proteasome function. Importantly, we show that FoxO1
https://www.frontiersin.org/articles/10.3389/fcell.2021.625715/full
Proteasome beta 1 Research Products: Novus BiologicalsProteasome beta 1 Research Products: Novus Biologicals
Proteasome beta 1 products available through Novus Biologicals. Browse our Proteasome beta 1 product catalog backed by our Guarantee+.
https://www.novusbio.com/common-name/proteasome-beta-1
Recombinant Human Proteasome beta 1 protein (ab88152) ReferencesRecombinant Human Proteasome beta 1 protein (ab88152) References
References for Abcams Recombinant Human Proteasome beta 1 protein (ab88152). Please let us know if you have used this product in your publication
http://www.abcam.com/recombinant-human-proteasome-beta-1-protein-ab88152-references.html
Plus itPlus it
C.1 Purification and Proteomic Mapping of Murine Liver 19S Proteasome Complexes D. Wang, M.-C. Koag, C. Zong, X. Li, A. Gomes, and P. Ping Department of Physiology and Medicine, Division of Cardiology, University of California, Los Angeles, CA Proteasome complexes play an indispensable role in maintaining cell homeostasis. 19S proteasome complexes, also known as the regulatory particles, are critical components of the 26S proteasome system by governing substrates entry and tuning the catalytic activities of the 20S proteasomes. Multiple studies on proteasome functions reported accumulatively a total of 22 mammalian 19S subunits forming two sub-complexes, the base and the lid. Unfortunately, a comprehensive proteomic blueprint of mammalian 19S complexes remains scarce; which has made it difficult to advance our understanding of the dynamics of proteasome function and substrate specificity. A key limitation is the technology challenges encountered in order to obtain purified 19S proteasome ...
https://www.mcponline.org/content/6/8_suppl_1/S53
Proteasome dysfunction induces muscle growth defects and protein aggregation<...
TY - JOUR. T1 - Proteasome dysfunction induces muscle growth defects and protein aggregation. AU - Kitajima, Yasuo. AU - Tashiro, Yoshitaka. AU - Suzuki, Naoki. AU - Warita, Hitoshi. AU - Kato, Masaaki. AU - Tateyama, Maki. AU - Ando, Risa. AU - Izumi, Rumiko. AU - Yamazaki, Maya. AU - Abe, Manabu. AU - Sakimura, Kenji. AU - Ito, Hidefumi. AU - Urushitani, Makoto. AU - Nagatomi, Ryoichi. AU - Takahashi, Ryosuke. AU - Aoki, Masashi. N1 - Publisher Copyright: © 2014. Published by The Company of Biologists Ltd.. PY - 2014. Y1 - 2014. N2 - The ubiquitin-proteasome and autophagy-lysosome pathways are the two major routes of protein and organelle clearance. The role of the proteasome pathway in mammalian muscle has not been examined in vivo. In this study, we report that the muscle-specific deletion of a crucial proteasomal gene, Rpt3 (also known as Psmc4), resulted in profound muscle growth defects and a decrease in force production in mice. Specifically, developing muscles in conditional ...
https://tohoku.pure.elsevier.com/en/publications/proteasome-dysfunction-induces-muscle-growth-defects-and-protein-
ATP Binding and ATP Hydrolysis Play Distinct Roles in the Function of 26S Proteasome<...
TY - JOUR. T1 - ATP Binding and ATP Hydrolysis Play Distinct Roles in the Function of 26S Proteasome. AU - Liu, Chang Wei. AU - Li, Xiaohua. AU - Thompson, David. AU - Wooding, Kerry. AU - Chang, Tsui ling. AU - Tang, Zhanyun. AU - Yu, Hongtao. AU - Thomas, Philip J.. AU - DeMartino, George N.. PY - 2006/10/6. Y1 - 2006/10/6. N2 - The 26S proteasome degrades polyubiquitinated proteins by an energy-dependent mechanism. Here we define multiple roles for ATP in 26S proteasome function. ATP binding is necessary and sufficient for assembly of 26S proteasome from 20S proteasome and PA700/19S subcomplexes and for proteasome activation. Proteasome assembly and activation may require distinct ATP binding events. The 26S proteasome degrades nonubiquitylated, unstructured proteins without ATP hydrolysis, indicating that substrate translocation per se does not require the energy of hydrolysis. Nonubiquitylated folded proteins and certain polyubiquitylated folded proteins were refractory to proteolysis. The ...
https://utsouthwestern.pure.elsevier.com/en/publications/atp-binding-and-atp-hydrolysis-play-distinct-roles-in-the-functio
Degradation of an intramitochondrial protein by the cytosolic proteasome | Journal of Cell ScienceDegradation of an intramitochondrial protein by the cytosolic proteasome | Journal of Cell Science
Mitochondrial uncoupling protein 2 (UCP2 is implicated in a wide range of pathophysiological processes, including immunity and diabetes mellitus, but its rapid degradation remains uncharacterized. Using pharmacological proteasome inhibitors, immunoprecipitation, dominant negative ubiqbiquitiuitin mutants, cellular fractionation and siRNA techniques, we demonstrate the involvement of the ubiquitin-proteasome system in the rapid degradation of UCP2. Importantly, we resolve the issue of whether intramitochondrial proteins can be degraded by the cytosolic proteasome by reconstituting a cell-free system that shows rapid proteasome-inhibitor-sensitive UCP2 degradation in isolated, energised mitochondria presented with an ATP regenerating system, ubiquitin and 26S proteasome fractions. These observations provide the first demonstration that a mitochondrial inner membrane protein is degraded by the cytosolic ubiquitin-proteasome system. ...
http://jcs.biologists.org/content/early/2010/01/26/jcs.060004
Immunoproteasome subunit LMP2 expression is deregulated in Sjögrens syndrome but not in other autoimmune disordersImmunoproteasome subunit LMP2 expression is deregulated in Sjögrens syndrome but not in other autoimmune disorders
Background: The proteasome system has a pivotal role in the control of the immune response, which suggests that it might be involved in the pathogenesis of autoimmune disorders.Objective: To investigate the expression profile of selected proteasomal genes in human peripheral blood mononuclear cells in patients with a variety of autoimmune diseases compared with healthy subjects.Methods: Real time quantitative RT-PCR was used to analyse the mRNA expression pattern of the proteasome activator subunits PA28\textgreeka and PA28\textgreekb and of constitutive proteasome and interferon-\textgreekg-inducible immunoproteasome subunits in peripheral blood mononuclear cells. Simultaneously, protein expression of selected proteasome subunits was quantified by immunoblotting.Results: Under systemic inflammatory conditions the proteasome subunits LMP2 (\textgreekb1i), LMP7 (\textgreekb5i), MECL1 (\textgreekb2i), and PA28\textgreeka were expressed abundantly at the protein level in the vast majority of ...
https://epub.ub.uni-muenchen.de/15009/
Tat-Binding Protein-1 (TBP-1), an ATPase of 19S Regulatory Particles of the 26S Proteasome, Enhances Androgen Receptor Function...Tat-Binding Protein-1 (TBP-1), an ATPase of 19S Regulatory Particles of the 26S Proteasome, Enhances Androgen Receptor Function...
Abstract: The 26S proteasome, which degrades ubiquitinated proteins, appears to contribute to the cyclical loading of androgen receptor (AR) to androgen response elements of target gene promoters; however, the mechanism whereby the 26S proteasome modulates AR recruitment remains unknown. Using yeast two-hybrid screening, we previously identified Tat-binding protein-1 (TBP-1), an adenosine triphosphatase of 19S regulatory particles of the 26S proteasome, as a transcriptional coactivator of thyroid hormone receptor. Independently, TBP-1-interacting protein (TBPIP) was also identified as a coactivator of several nuclear receptors, including AR. Here, we investigated whether TBP-1 could interact with and modulate transcriptional activation by AR cooperatively with TBPIP. TBP-1 mRNA was ubiquitously expressed in human tissues, including the testis and prostate, as well as in LNCaP cells. TBP-1 directly bound TBPIP through the amino-terminal domain possessing the leucine zipper structure. AR is ...
https://scialert.net/asci/ascidetail.php?doi=endo.2009.3283.3290&kw=
KEGG PATHWAY: Proteasome - Streptomyces violaceusniger
The proteasome is a protein-destroying apparatus involved in many essential cellular functions, such as regulation of cell cycle, cell differentiation, signal transduction pathways, antigen processing for appropriate immune responses, stress signaling, inflammatory responses, and apoptosis. It is capable of degrading a variety of cellular proteins in a rapid and timely fashion and most substrate proteins are modified by ubiquitin before their degradation by the proteasome. The proteasome is a large protein complex consisting of a proteolytic core called the 20S particle and ancillary factors that regulate its activity in various ways. The most common form is the 26S proteasome containing one 20S core particle and two 19S regulatory particles that enable the proteasome to degrade ubiquitinated proteins by an ATP-dependent mechanism. Another form is the immunoproteasome containing two 11S regulatory particles, PA28 alpha and PA28 beta, which are induced by interferon gamma under the conditions of ...
http://www.genome.jp/kegg-bin/show_pathway?svl03050
KEGG PATHWAY: Proteasome - Streptomyces avermitilis
The proteasome is a protein-destroying apparatus involved in many essential cellular functions, such as regulation of cell cycle, cell differentiation, signal transduction pathways, antigen processing for appropriate immune responses, stress signaling, inflammatory responses, and apoptosis. It is capable of degrading a variety of cellular proteins in a rapid and timely fashion and most substrate proteins are modified by ubiquitin before their degradation by the proteasome. The proteasome is a large protein complex consisting of a proteolytic core called the 20S particle and ancillary factors that regulate its activity in various ways. The most common form is the 26S proteasome containing one 20S core particle and two 19S regulatory particles that enable the proteasome to degrade ubiquitinated proteins by an ATP-dependent mechanism. Another form is the immunoproteasome containing two 11S regulatory particles, PA28 alpha and PA28 beta, which are induced by interferon gamma under the conditions of ...
http://www.genome.jp/kegg-bin/show_pathway?sma03050
Proteasome dysfunction induces muscle growth defects and protein aggregation | Journal of Cell ScienceProteasome dysfunction induces muscle growth defects and protein aggregation | Journal of Cell Science
The ubiquitin-proteasome and autophagy-lysosome pathways are the two major routes of protein and organelle clearance. The role of the proteasome pathway in mammalian muscle has not been examined in vivo. In this study, we report that the muscle-specific deletion of a crucial proteasomal gene, Rpt3, resulted in profound muscle growth defects and a decrease in force production in mice. Specifically, developing muscles in conditional Rpt3-knockout animals showed dysregulated proteasomal activity. The autophagy pathway was upregulated, but the process of autophagosome formation was impaired. A microscopic analysis revealed the accumulation of basophilic inclusions and disorganization of the sarcomeres in young adult mice. Our results suggest that appropriate proteasomal activity is important for muscle growth and for maintaining myofiber integrity in collaboration with autophagy pathways. The deletion of a component of the proteasome complex contributed to myofiber degeneration and weakness in ...
http://jcs.biologists.org/content/early/2014/11/03/jcs.150961
RPN14 - 26S proteasome regulatory subunit RPN14 - Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Bakers yeast) - RPN14...RPN14 - 26S proteasome regulatory subunit RPN14 - Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Bakers yeast) - RPN14...
Acts as a regulatory subunit of the 26 proteasome which is involved in the ATP-dependent degradation of ubiquitinated proteins. Is not a genuine component of the 26S proteasome, but an auxiliary factor that interacts with the proteasomal ATPase of 19S regulatory particle (RP). Acts as a chaperone which regulates the highly structured assembly of the 19S regulatory particle. Involved in the substrate specificity of the 26S proteasome and is especially involved in the degradation of ubiquitinated GCN4. May contribute to the stability of the 26S proteasome in some stress conditions.
http://www.uniprot.org/uniprot/P53196
PSMC5 - Gemini GenomicsPSMC5 - Gemini Genomics
Description: The 26S proteasome is a multicatalytic proteinase complex with a highly ordered structure composed of 2 complexes, a 20S core and a 19S regulator. The 20S core is composed of 4 rings of 28 non-identical subunits; 2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta subunits. The 19S regulator is composed of a base, which contains 6 ATPase subunits and 2 non-ATPase subunits, and a lid, which contains up to 10 non-ATPase subunits. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. This gene encodes one of the ATPase subunits, a member of the triple-A family of ATPases which have a chaperone-like activity. In addition to participation in proteasome functions, this subunit may participate in transcriptional regulation since it has been ...
https://gemini-genomics.com/psmc5/
Age-dependent inhibition of proteasome chymotrypsin-like activity in the retina<...Age-dependent inhibition of proteasome chymotrypsin-like activity in the retina<...
TY - JOUR. T1 - Age-dependent inhibition of proteasome chymotrypsin-like activity in the retina. AU - Kapphahn, Rebecca J.. AU - Bigelow, Erin J.. AU - Ferrington, Deborah A.. PY - 2007/4/1. Y1 - 2007/4/1. N2 - The proteasome plays a fundamental role in processes essential for cell viability. A loss in proteasome function has been associated with aging, as well as a number of age-related diseases. Defining the mechanism(s) behind this loss in function will add important information regarding the molecular basis for aging. In the current study, we performed an age-based comparison of proteasome function and composition of subunits and regulatory proteins in the neural retina and retinal pigment epithelium (RPE) in Fischer 344 rats. In the RPE, there was no age-dependent difference in activity, subunit composition, or content of proteasome regulators, PA28 and PA700. In contrast, the aged neural retina demonstrated a significant reduction in the chymotrypsin-like activity and decreased degradation ...
https://experts.umn.edu/en/publications/age-dependent-inhibition-of-proteasome-chymotrypsin-like-activity
Psmb11 - Proteasome subunit beta type-11 precursor - Mus musculus (Mouse) - Psmb11 gene & proteinPsmb11 - Proteasome subunit beta type-11 precursor - Mus musculus (Mouse) - Psmb11 gene & protein
The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity. Incorporated instead of PSMB5 or PSMB8, this unit reduces the chymotrypsin-like activity of the proteasome. Plays a pivotal role in development of CD8-positive T-cells.
http://www.uniprot.org/uniprot/Q8BG41
A humanized yeast proteasome identifies unique binding modes of inhibitors for the immunosubunit β5i | The EMBO JournalA humanized yeast proteasome identifies unique binding modes of inhibitors for the immunosubunit β5i | The EMBO Journal
Protein breakdown by the ubiquitin‐proteasome system ensures cell survival and proliferation. The 20S proteasome core particle (CP) constitutes the heart of this non‐lysosomal protein degradation pathway. In mammals, three different CP types are known: the constitutive proteasome (cCP), the immunoproteasome (iCP), and the thymoproteasome (tCP) (Murata et al, 2007; Groettrup et al, 2010). All of them are built of seven different α‐ and seven different β‐subunits that are stacked in four heptameric rings around a central pore. Each type of CP incorporates a distinct set of catalytically active β1, β2 and β5 subunits (cCP: β1c, β2c and β5c; iCP: β1i, β2i and β5i; tCP: β1i, β2i and β5t) (Groll et al, 1997; Unno et al, 2002; Murata et al, 2007; Huber et al, 2012; Harshbarger et al, 2015). These subunits employ the same mechanism of peptide bond hydrolysis (Huber et al, 2012, 2016), but display different substrate specificities. Because of its pivotal biological role, the ...
http://emboj.embopress.org/content/35/23/2602
The ubiquitin-26S proteasome system at the nexus of plant biologyThe ubiquitin-26S proteasome system at the nexus of plant biology
Plants, like other eukaryotes, rely on proteolysis to control the abundance of key regulatory proteins and enzymes. Strikingly, genome-wide studies have revealed that the ubiquitin-26S proteasome system (UPS) in particular is an exceedingly large and complex route for protein removal, occupying near …
https://pubmed.ncbi.nlm.nih.gov/19424292/?dopt=Abstract
Base-CP proteasome can serve as a platform for stepwise lid formation<...
TY - JOUR. T1 - Base-CP proteasome can serve as a platform for stepwise lid formation. AU - Yu,Zanlin. AU - Livnat-Levanon,Nurit. AU - Kleifeld,Oded. AU - Mansour,Wissam. AU - Nakasone,Mark A.. AU - Castaneda,Carlos A.. AU - Dixon,Emma K.. AU - Fushman,David. AU - Reis,Noa. AU - Pick,Elah. AU - Glickman,Michael H.. PY - 2015. Y1 - 2015. N2 - 26S proteasome, a major regulatory protease in eukaryotes, consists of a 20S proteolytic core particle (CP) capped by a 19S regulatory particle (RP). The 19S RP is divisible into base and lid sub-complexes. Even within the lid, subunits have been demarcated into two modules: module 1 (Rpn5, Rpn6, Rpn8, Rpn9 and Rpn11), which interacts with both CP and base sub-complexes and module 2 (Rpn3, Rpn7, Rpn12 and Rpn15) that is attached mainly to module 1. We now show that suppression of RPN11 expression halted lid assembly yet enabled the base and 20S CP to pre-assemble and form a base-CP. A key role for Regulatory particle non-ATPase 11 (Rpn11) in bridging lid ...
https://experts.syr.edu/en/publications/base-cp-proteasome-can-serve-as-a-platform-for-stepwise-lid-forma
Crude and purified proteasome activity assays are affected by type of microplate<...
TY - JOUR. T1 - Crude and purified proteasome activity assays are affected by type of microplate. AU - Cui, Ziyou. AU - Gilda, Jennifer E.. AU - Gomes, Aldrin V. PY - 2014. Y1 - 2014. N2 - Measurement of proteasome activity is fast becoming a commonly used assay in many laboratories. The most common method to measure proteasome activity involves measuring the release of fluorescent tags from peptide substrates in black microplates. Comparisons of black plates used for measuring fluorescence with different properties show that the microplate properties significantly affect the measured activities of the proteasome. The microplate that gave the highest reading of trypsin-like activity of the purified 20S proteasome gave the lowest reading of chymotrypsin-like activity of the 20S proteasome. Plates with medium binding surfaces from two different companies showed an approximately 2-fold difference in caspase-like activity for purified 20S proteasomes. Even standard curves generated using free ...
https://ucdavis.pure.elsevier.com/en/publications/crude-and-purified-proteasome-activity-assays-are-affected-by-typ
Ubiquitin Proteasome Market Projected to Garner Significant Revenues by 2019 -end - The Global Health NewsUbiquitin Proteasome Market Projected to Garner Significant Revenues by 2019 -end - The Global Health News
Research in the field of ubiquitin proteasome is expanding exponentially. For instance, intensive research is going on in the field of applications of ubiquitin proteasome system in the treatment of cancer, as the pharmacological inhibition properties of proteasomes can be effective in cancer treatment. Potential sites of therapeutic interventions are also under research and the selective inhibition of disease specific components is also being studied for the purpose of developing treatments for diseases such as neurodegenerative disorders. This indicates a bright future market potential depending upon the time required for commercialization. Currently, there is only one approved ubiquitin proteasome system product available in the market named Velcade. In 2009, total sales of Velcade were estimated to be 1.4 billion and being the only approved drug, its sales are expected to achieve growth at a high compounded annual growth rate ...
https://theglobalhealthnews.com/ubiquitin-proteasome-market-projected-garner-significant-revenues-2019-end/
Targeting the Ubiquitin - Proteasome PathwayTargeting the Ubiquitin - Proteasome Pathway
Protein turnover is crucial in maintaining cellular homeostasis and this process is largely controlled by the Ubiquitin Proteasome Pathway (UPP). The pathway consists of an enzymatic cascade that links the polypeptide cofactor Ubiquitin to specific protein targets, which mark them for degradation by the proteasome. This cascade is highly regulated and impacts virtually all cellular processes including cell cycle progression, cell proliferation, cell differentiation and apoptosis. Malfunction of the UPP has been implicated in the development of diseases such as cancer, immune disorders and neurodegeneration. ...
https://www.soci.org/events/targeting-the-ubiquitin--proteasome-pathway
Regulation of ubiquitin-proteasome and autophagy pathways after acute LPS and epoxomicin administration in mice | BMC...Regulation of ubiquitin-proteasome and autophagy pathways after acute LPS and epoxomicin administration in mice | BMC...
The ubiquitin-proteasome pathway (UPP) is a major protein degradation pathway that is activated during sepsis and has been proposed as a therapeutic target for preventing skeletal muscle loss due to cachexia. Although several studies have investigated the modulation of proteasome activity in response to LPS administration, none have characterized the overall UPP response to LPS administration in the fate of proteasome inhibition. Here, we determined the modulation pattern of the main key components of the UPP in the gastrocnemius (GAS) of mice during the acute phase of lipopolysaccharide (LPS)-mediated endotoxemia (7.5 mg/kg - 8 h) by measuring all three β1, β2 and β5 activites of the 20S and 26S proteasomes, the levels of steady state polyubiquitinated proteins, mRNA levels of muscle ligases, as well as signaling pathways regulating the UPP. Another goal was to assess the effects of administration of a specific proteasome inhibitor (epoxomicin, 0.5 mg/kg) on UPP response to sepsis. The acute phase
https://bmcmusculoskeletdisord.biomedcentral.com/articles/10.1186/1471-2474-15-166
PDCD5 mediates ubiquitin-dependent proteasomal degradat | Open-iPDCD5 mediates ubiquitin-dependent proteasomal degradat | Open-i
PDCD5 mediates ubiquitin-dependent proteasomal degradation of HDAC3 via C-terminal cleavage of HDAC3.(a) MG132 treatment induces accumulation of cleaved HDAC3.
https://openi.nlm.nih.gov/detailedresult.php?img=PMC4490383_ncomms8390-f3&req=4
The C terminus of Rpt3, an ATPase subunit of PA700 (19 S) regulatory complex, is essential for 26 S proteasome assembly but not...
TY - JOUR. T1 - The C terminus of Rpt3, an ATPase subunit of PA700 (19 S) regulatory complex, is essential for 26 S proteasome assembly but not for activation. AU - Kumar, Brajesh. AU - Kim, Young Chan. AU - DeMartino, George N.. N1 - Copyright: Copyright 2011 Elsevier B.V., All rights reserved.. PY - 2010/12/10. Y1 - 2010/12/10. N2 - PA700, the 19 S regulatory subcomplex of the 26 S proteasome, contains a heterohexameric ring of AAA subunits (Rpt1 to -6) that forms the binding interface with a heteroheptameric ring of α subunits (α1 to -7) of the 20 S proteasome. Binding of these subcomplexes is mediated by interactions of C termini of certain Rpt subunits with cognate binding sites on the 20 S proteasome. Binding of two Rpt subunits (Rpt2 and Rpt5) depends on their last three residues, which share an HbYX motif (where Hb is a hydrophobic amino acid) and open substrate access gates in the center of the α ring. The relative roles of other Rpt subunits for proteasome binding and activation ...
https://utsouthwestern.pure.elsevier.com/en/publications/the-c-terminus-of-rpt3-an-atpase-subunit-of-pa700-19-s-regulatory
The novel β2-selective proteasome inhibitor LU-102 synergizes with bortezomib and carfilzomib to overcome proteasome inhibitor...The novel β2-selective proteasome inhibitor LU-102 synergizes with bortezomib and carfilzomib to overcome proteasome inhibitor...
Bortezomib-resistant myeloma cells contain increased proteolytic processing capacity, including upregulation of the β2 proteasome activity not targeted by bortezomib.20 We hypothesized that β2 proteasome activity contributes to bortezomib resistance and may, therefore, represent a rational target for the treatment of proteasome inhibitor-resistant myeloma.. We here describe the effect of LU-102, the first β2/β2i-selective proteasome inhibitor available for pre-clinical studies in myeloma, on bortezomib- and carfilzomib-resistant myeloma cells. Selective elimination of β2 proteasome activity alone was not sufficient to induce a meaningful cytotoxic effect in bortezomib- or carfilzomib-resistant myeloma cells. However, the combination of LU-102 with bortezomib or carfilzomib was highly potent to overcome bortezomib- or carfilzomib-resistance. This was observed not only in a proteasome inhibitor-adapted myeloma cell line model that mirrors several of the biological features of bortezomib ...
http://www.haematologica.org/content/100/10/1350
Effects of proteasome inhibition on cisplatin induced DNA damage responses in human cellsEffects of proteasome inhibition on cisplatin induced DNA damage responses in human cells
The proteasome is the main site of protein degradation in human cells, and plays a major role in the regulation of cellular processes including cell cycle progression, DNA repair and the DNA damage response. Proteasome inhibition is emerging as a new anti-cancer strategy, with the development of bortezomib for the treatment of patients with multiple myeloma. Proteasome inhibitors can be used either as single agents or in conjunction with other cancer treatments. Proteasome inhibitors can sensitise cancer cell lines to routinely-used cancer treatments including the platinum-based anti-cancer drug, cisplatin. The aim of this research was to investigate the effect of proteasome inhibition on cisplatininduced DNA damage responses in human cells, including cell viability, cell cycle arrest and the phosphorylation of DNA damage response proteins. The proteasome inhibitor MG132 sensitised the pol n-deficient human fibroblast cell line XP30RO to cisplatin. MG132 treatment induced strong cell cycle ...
https://aran.library.nuigalway.ie/xmlui/handle/10379/2671
HSP70 Inhibition Leads to the Activation of Proteasomal System under Mild Hyperthermia Conditions in Young and Senescent...
Aging has been characterized with the accumulation of oxidized proteins, as a consequence of progressive decline in proteostasis capacity. Among others, proteasomal system is an efficient protein turnover complex to avoid aggregation of oxidized proteins. Heat shock protein 70 (HSP70) is another critical player that is involved in some key processes including the correct folding of misfolded proteins and targeting aggregated proteins to the proteasome for rapid degradation. The aim of this study was to determine the role of proteasomal system and heat shock proteins to maintain proteome balance during replicative senescence in mild hyperthermia conditions. Our results demonstrated that HSP40/70 machinery is induced by mild hyperthermia conditions independent from senescence conditions. Since HSP70 is largely responsible for the rapidly inducible cell protection following hyperthermia, the activation of heat shock response resulted in the elevation of HSP40/70 expressions as well as the ...
https://avesis.acibadem.edu.tr/yayin/1f371e39-0b81-4e52-9f78-dcbed3cc1115/hsp70-inhibition-leads-to-the-activation-of-proteasomal-system-under-mild-hyperthermia-conditions-in-young-and-senescent-fibroblasts
Inhibition of proteasome activities and subunit-specific amino-terminal threonine modification by lactacystin | ScienceInhibition of proteasome activities and subunit-specific amino-terminal threonine modification by lactacystin | Science
Lactacystin is a Streptomyces metabolite that inhibits cell cycle progression and induces neurite outgrowth in a murine neuroblastoma cell line. Tritium-labeled lactacystin was used to identify the 20S proteasome as its specific cellular target. Three distinct peptidase activities of this enzyme complex (trypsin-like, chymotrypsin-like, and peptidylglutamyl-peptide hydrolyzing activities) were inhibited by lactacystin, the first two irreversibly and all at different rates. None of five other proteases were inhibited, and the ability of lactacystin analogs to inhibit cell cycle progression and induce neurite outgrowth correlated with their ability to inhibit the proteasome. Lactacystin appears to modify covalently the highly conserved amino-terminal threonine of the mammalian proteasome subunit X (also called MB1), a close homolog of the LMP7 proteasome subunit encoded by the major histocompatibility complex. This threonine residue may therefore have a catalytic role, and subunit X/MB1 may be a ...
https://science.sciencemag.org/content/268/5211/726?ijkey=c134a72fc1d439a03687b24494783b111c0a78cf&keytype2=tf_ipsecsha
Degradation and beyond: Control of androgen receptor activity by the proteasome system | Cellular & Molecular Biology Letters |...Degradation and beyond: Control of androgen receptor activity by the proteasome system | Cellular & Molecular Biology Letters |...
The androgen receptor (AR) is a transcription factor belonging to the family of nuclear receptors which mediates the action of androgens in the development of urogenital structures. AR expression is regulated post-translationally by the ubiquitin/proteasome system. This regulation involves more complex mechanisms than typical degradation. The ubiquitin/proteasome system may regulate AR via mechanisms that do not engage in receptor turnover. Given the critical role of AR in sexual development, this complex regulation is especially important. Deregulation of AR signalling may be a causal factor in prostate cancer development. AR is the main target in prostate cancer therapies. Due to the critical role of the ubiquitin/proteasome system in AR regulation, current research suggests that targeting AR degradation is a promising approach.
https://cmbl.biomedcentral.com/articles/10.2478/s11658-006-0011-9
Dissecting a role of a charge and conformation of Tat2 peptide in allosteric regulation of 20S proteasome<...Dissecting a role of a charge and conformation of Tat2 peptide in allosteric regulation of 20S proteasome<...
TY - JOUR. T1 - Dissecting a role of a charge and conformation of Tat2 peptide in allosteric regulation of 20S proteasome. AU - Witkowska, Julia. AU - Karpowicz, Przemysław. AU - Gaczynska, Maria. AU - Osmulski, Pawel A.. AU - Jankowska, Elzbieta. PY - 2014/8. Y1 - 2014/8. N2 - Proteasome is a proteolytic factory that constitutes an essential part of the ubiquitin-proteasome pathway. The involvement of proteasome in regulation of all major aspects of cellular physiology makes it an attractive drug target. So far, only inhibitors of the proteasome entered the clinic as anti-cancer drugs. However, proteasome regulators may also be useful for treatment of inflammatory and neurodegenerative diseases. We established in our previous studies that the peptide Tat2, comprising the basic domain of HIV-1 Tat protein: R49KKRRQRR56, supplemented with Q66DPI 69 fragment, inhibits the 20S proteasome in a noncompetitive manner. Mechanism of Tat2 likely involves allosteric regulation because it competes with ...
https://scholars.uthscsa.edu/en/publications/dissecting-a-role-of-a-charge-and-conformation-of-tat2-peptide-in
Endoplasmic reticulum stress caused by aggregate-prone proteins containing homopolymeric amino acids. | PubFactsEndoplasmic reticulum stress caused by aggregate-prone proteins containing homopolymeric amino acids. | PubFacts
Many human proteins have homopolymeric amino acid (HPAA) tracts, but their physiological functions or cellular effects are not well understood. Previously, we expressed 20 HPAAs in mammalian cells and showed characteristic intracellular localization, in that hydrophobic HPAAs aggregated strongly and caused high cytotoxicity in proportion to their hydrophobicity. In the present study, we investigated the cytotoxicity of these aggregate-prone hydrophobic HPAAs, assuming that the ubiquitin proteasome system is impaired in the same manner as other well-known aggregate-prone polyglutamine-containing proteins. Some highly hydrophobic HPAAs caused a deficiency in the ubiquitin proteasome system and excess endoplasmic reticulum stress, leading to apoptosis. These results indicate that the property of causing excess endoplasmic reticulum stress by proteasome impairment may contribute to the strong cytotoxicity of highly hydrophobic HPAAs, and proteasome impairment and the resulting excess endoplasmic ...
https://www.pubfacts.com/detail/17922840/Endoplasmic-reticulum-stress-caused-by-aggregate-prone-proteins-containing-homopolymeric-amino-acids
26S Proteasome regulatory subunit p55 - NBP1-56983 | acris-antibodies.com
26S Proteasome regulatory subunit p55, 50 µg. The 26S proteasome is a multicatalytic proteinase complex with a highly ordered structure composed of 2 complexes, a 20S core and a 19S regulator.
https://www.acris-antibodies.com/antibodies/primary-antibodies/26s-proteasome-regulatory-subunit-p55-nbp1-56983.htm
26S Proteasome regulatory subunit p55 - NBP1-56980 | acris-antibodies.com
26S Proteasome regulatory subunit p55, 50 µg. The 26S proteasome is a multicatalytic proteinase complex with a highly ordered structure composed of 2 complexes, a 20S core and a 19S regulator.
https://www.acris-antibodies.com/antibodies/primary-antibodies/26s-proteasome-regulatory-subunit-p55-nbp1-56980.htm
Proteasome-dependent degradation of the human estrogen receptor<...
TY - JOUR. T1 - Proteasome-dependent degradation of the human estrogen receptor. AU - Nawaz, Zafar. AU - Lonard, David M.. AU - Dennis, Andrew P.. AU - Smith, Carolyn L.. AU - OMalley, Bert W.. PY - 1999/3/2. Y1 - 1999/3/2. N2 - In eukaryotic cells, the ubiquitin-proteasome pathway is the major mechanism for the targeted degradation of proteins with short half-lives. The covalent attachment of ubiquitin to lysine residues of targeted proteins is a signal for the recognition and rapid degradation by the proteasome, a large multi-subunit protease. In this report, we demonstrate that the human estrogen receptor (ER) protein is rapidly degraded in mammalian cells in an estradiol-dependent manner. The treatment of mammalian cells with the proteasome inhibitor MG132 inhibits activity of the proteasome and blocks ER degradation, suggesting that ER protein is turned over through the ubiquitin- proteasome pathway. In addition, we show that in vitro ER degradation depends on ubiquitin-activating E1 ...
https://miami.pure.elsevier.com/en/publications/proteasome-dependent-degradation-of-the-human-estrogen-receptor
Resveratrol protects leukemic cells against cytotoxicity induced by proteasome inhibitors via induction of FOXO1 and p27Kip1 |...Resveratrol protects leukemic cells against cytotoxicity induced by proteasome inhibitors via induction of FOXO1 and p27Kip1 |...
Single agent of proteasome inhibitor resulted in significant responses in leukemic cells and the combination of proteasome inhibitors and other chemotherapeutic drugs enhanced its antitumoral efficacy [3, 33-37]. Initially, the experiments were planned to test whether resveratrol could sensitized K562 cells to the anticancer actions of proteasome inhibitors. To our surprise, resveratrol did not promote, but rather attenuated the apoptotic effects of MG132 in cultured K562 cells. We further extended our investigation using a panel of leukemic cells and found that resveratrol also attenuated the cytotoxic actions of MG132 in NB4, U937, Raji and Daudi cells. Furthermore, resveratrol also compromised the apoptotic effects of other three structurally different proteasome inhibitors, PSI, epoxomicin and lactacystin. This was consistent with the previous study that resveratrol exerted its protective effects against proteasome inhibitor-induced cellular damages in human skeletal myotubes [38]. ...
https://bmccancer.biomedcentral.com/articles/10.1186/1471-2407-11-99
A Proteasome Cap Subunit Required for Spindle Pole Body Duplication in Yeast | JCBA Proteasome Cap Subunit Required for Spindle Pole Body Duplication in Yeast | JCB
We have described the identification and characterization of PCS1, an essential yeast gene whose predicted product shows a high level of sequence identity with a family of ATPases that are components of the 19S proteasome cap. The 67% identity between Pcs1p and p42, a known human 26S proteasome regulatory subunit (25), provides strong evidence that Pcs1p is itself a proteasome subunit. This idea has recently been confirmed biochemically (83). The p42 subunit has been identified not only as a component of the proteasome cap (also known as PA700) but also of the proteasome modulator, a second complex that enhances cap activation of proteolytic activity (18). Whether a modulator of this sort also exists in S. cerevisiae is unknown.. It has been suggested that different ATPases within the 19S cap might serve to recognize distinct degradation substrates; a structural model for how this recognition specificity might be mediated has been proposed by Rechsteiner et al. (78). These authors note that ...
http://jcb.rupress.org/content/137/3/539
Struktur und Funktion der 20S Proteasomen aus Organen Listeria monocytogenes infizierter MäuseStruktur und Funktion der 20S Proteasomen aus Organen Listeria monocytogenes infizierter Mäuse
The proteasome system of the cell is responsible for the degradation of proteins and plays a central role in the generation of epitopes which are presented to cytotoxic T-lymphocytes (CTLs) on MHC-class-I molecules. The stimulation of cells by interferon-gamma (IFNgamma) leads to the formation of immunoproteasomes that show an improved generation of many MHC-class-I epitopes compared to constitutive proteasomes. In healthy mice, immunoproteasomes are mainly expressed in the lymphatic tissues, whereas the non-lymphatic organs predominantly contain constitutive proteasomes. In this project the effect of Listeria monocytogenes infection on murine 20S proteasomes derived from the liver, spleen, small intestine and colon were investigated. The structure of the isolated proteasomes was analyzed by two-dimensional gel electrophoresis and western blots while the function was studied by in vitro processing of three oligomeric peptide substrates. Identification and quantification of the processing ...
https://edoc.hu-berlin.de/handle/18452/15928
Martina Bazzaro, PhD | Department of Obstetrics, Gynecology and Womens Health - University of MinnesotaMartina Bazzaro, PhD | Department of Obstetrics, Gynecology and Womens Health - University of Minnesota
Study of the mechanisms underlying breast and ovarian cancer development and progression. Dr. Bazzaros laboratory is interested in studying abnormalities of protein degradation pathways in breast and ovarian cancer. The Ubiquitin-Proteasome-System (UPS) is responsible for degradation of over 90% of short-lived intracellular proteins. Protein degradation through Ubiquitin-Proteasome-System is a multistep process that begins with de-ubiquitination of ubiquitin-tagged target molecules by de-ubiquitinating enzymes following their entrance in the 20S catalytic chamber of the proteasomes were the actual degradation occurs. The polypeptide targets of the proteasome include proteins involved in cell cycle progression, survival and inflammation and while the ubiquitin-dependent proteasomal degradation is crucial for both normal and malignant cells the higher demand for metabolic/catabolic activity associated with the malignant phenotype renders the ubiquitin-proteasome pathway a suitable tool for cancer ...
https://www.obgyn.umn.edu/bio/obgyn-faculty/martina-bazzaro
Ubiquitin-proteasome dependent mitochondrial protein quality control - edocUbiquitin-proteasome dependent mitochondrial protein quality control - edoc
Dysfunctional mitochondria cause many neurodegenerative disorders and with aging in general, mechanisms of mitochondrial quality control are essential for cellular function. Keeping mitochondria in a healthy state is a complex process, which is tightly regulated by several mitochondrial quality control systems. An ubiquitin-mediated proteasome-dependent protein degradation pathway, termed outer mitochondrial-associated degradation (OMMAD), was recently described. OMMAD provides mitochondrial protein quality control to prevent mitochondrial damage. Up until now, four outer mitochondrial membrane-anchored RING finger ubiquitin ligases as well as the AAA-ATPase p97 were described as OMMAD components. Here, we further characterize the mitochondrial RING finger protein MARCH9. We found that MARCH9 is an unstable protein degraded in a proteasomal-dependent manner. Furthermore MARCH9 interacts physically with both mitofusins, Mfn1 and Mfn2, both involved in the mitochondrial fusion. The ...
http://edoc.unibas.ch/32504/
The proteasome regulates the UV-induced activation of the AP-1-like transcription factor Gcn4<...
TY - JOUR. T1 - The proteasome regulates the UV-induced activation of the AP-1-like transcription factor Gcn4. AU - Stitzel, M. L.. AU - Durso, R.. AU - Reese, J. C.. PY - 2001/1/15. Y1 - 2001/1/15. N2 - The proteasome is well known for its regulation of the cell cycle and degradation of mis-folded proteins, yet many of its functions are still unknown. We show that RPN11, a gene encoding a subunit of the regulatory cap of the proteasome, is required for UV-stimulated activation of Gcn4p target genes, but is dispensable for their activation by the general control pathway. We provide evidence that RPN11 functions downstream of RAS2, and show that mutation of two additional proteasome subunits results in identical phenotypes. Our analysis defines a novel function of the proteasome: regulation of the RAS- and AP-1 transcription factor-dependent UV resistance pathway.. AB - The proteasome is well known for its regulation of the cell cycle and degradation of mis-folded proteins, yet many of its ...
https://pennstate.pure.elsevier.com/en/publications/the-proteasome-regulates-the-uv-induced-activation-of-the-ap-1-li
SMART: UIM domain annotationSMART: UIM domain annotation
The Ubiquitin Interacting Motif (UIM), or LALAL-motif, is a stretch of about 20 amino acid residues, which was first described in the 26S proteasome subunit PSD4/RPN-10 that is known to recognise ubiquitin [(PUBMED:9488668),(PUBMED:11406394)]. In addition, the UIM is found, often in tandem or triplet arrays, in a variety of proteins either involved in ubiquitination and ubiquitin metabolism, or known to interact with ubiquitin-like modifiers. Among the UIM proteins are two different subgroups of the UBP (ubiquitin carboxy-terminal hydrolase) family of deubiquitinating enzymes, one F-box protein, one family of HECT-containing ubiquitin-ligases (E3s) from plants, and several proteins containing ubiquitin-associated UBA and/or UBX domains [(PUBMED:12062168)]. In most of these proteins, the UIM occurs in multiple copies and in association with other domains such as UBA (IPR015940), UBX (IPR001012), ENTH, EH (IPR000261), VHS (IPR002014), SH3 (IPR001452), HECT (IPR000569), VWFA (IPR002035), EF-hand ...
http://smart.embl.de/smart/do_annotation.pl?DOMAIN=UIM&START=888&END=907&E_VALUE=3.32e0&TYPE=SMART&BLAST=SEEDMIEWAKRESEREEEQR
Plus itPlus it
2879 The ubiquitin-proteasome pathway controls the turnover of many oncoproteins and tumor suppressors, thus playing a major role in cancer development. This pathway also regulates the stability of Smads. Recent studies have shown that R-Smads are post-translationally modified by ubiquitin and can be irreversibly removed from the cell by the proteasome-mediated degradation system. Ubiquitination, the covalent attachment of ubiquitin to proteins, predominantly serves to target proteins for their degradation by 26S proteasomes. Conjugation of ubiquitin is accomplished by an enzymatic cascade involving E1, E2 and E3 enzymes. Ubiquitin E3 ligases play the most significant role in substrate specificity. Smad4/DPC4 is a common signal transducer in TGF-β signaling. Contrary to R-Smads, our knowledge on the regulation of Smad4 by ubiquitin/proteasome pathway is rather limited. Although the ubiquitin-proteasome pathway has been established as one mechanism of regulating Smad4 stability, the specific ...
http://cancerres.aacrjournals.org/content/65/9_Supplement/676.3
The 26S proteasome is required for estrogen receptor-alpha and coactivator turnover and for efficient estrogen receptor-alpha...The 26S proteasome is required for estrogen receptor-alpha and coactivator turnover and for efficient estrogen receptor-alpha...
Estrogen receptor-alpha (ER alpha) is downregulated in the presence of its cognate ligand, estradiol (E2), through the ubiquitin proteasome pathway. Here, we show that ubiquitin proteasome function is required for ER alpha to serve as a transcriptional activator. Deletion of the last 61 amino acids …
https://pubmed.ncbi.nlm.nih.gov/10911988/?dopt=Abstract
Sakata-CV | Max Planck Institute of BiochemistrySakata-CV | Max Planck Institute of Biochemistry
Pack CG, Yukii H, Toh-e A, Kudo T, Tsuchiya H, Kaiho A, Sakata E, Murata S, Yokosawa H, Sako Y, Baumeister W, Tanaka K, Saeki Y, Quantitative live-cell imaging reveals spatio-temporal dynamics and cytoplasmic assembly of the 26S proteasome. Nat Commun. 5:3396 (2014). Bohn S, Sakata E, Beck F, Pathare GR, Schnitger J, Nágy I, Baumeister W, Förster F. Localization of the regulatory particle subunit Sem1 in the 26S proteasome. Biochem Biophys Res Commun. 435(2):250-354 (2013). Fernández-Busnadiego R, Asano S, Oprisoreanu AM, Sakata E, Doengi M, Kochovski Z, Zürner M, Stein V, Schoch S, Baumeister W, Lucić V. Cryo-electron tomography reveals a critical role of RIM1a in synaptic vesicle tethering. J Cell Biol. 201(5):725-740, (2013). Sugiyama M, Sahashi H, Kurimoto E, Takata S, Yagi H, Kanai K, Sakata E, Minami Y, Tanaka K, Kato K. Spatial arrangement and functional role of α subunits of proteasome activator PA28 in hetero-oligomeric form. Biochem Biophys Res Commun. 432(1):141-145, ...
http://www.biochem.mpg.de/4863875/Sakata-CV
Share it: Plastidäre Vorläuferproteine im Cytosol : Import vs. DegradationShare it: Plastidäre Vorläuferproteine im Cytosol : Import vs. Degradation
The majority of Arabidopsis thaliana plastid proteins is nuclear encoded and has to be synthesized in the cytosol as preproteins. Plastid preproteins are modified in the cytosol and subject to quality control prior to their organellar translocation. We show here that the second amino acid of plastid preproteins determines N-terminal modifications and influences import efficiency or stability in transiently transformed protoplasts. Further inhibition of the 26S proteasome leads to accumulation of preproteins, supporting a connection between the ubiquitin-proteasome system (UPS) and preprotein degradation. The mutation of the regulatory proteasome subunit Rpn8A in the plastid protein import mutant 2 (ppi2) background leads to partial rescue of the ppi2 plastid phenotype. A proteome-wide comparison of ppi2 with the rpn8a ppi2 double mutant showed among other things increased abundance of photosynthetic proteins. These results refer to regulatory effects of the proteasome on the plastid biogenesis. ...
https://opendata.uni-halle.de/handle/123456789/1/simple-search?query=&sort_by=score&order=desc&rpp=10&filter_field_1=subject&filter_type_1=equals&filter_value_1=572&filter_field_2=subject&filter_type_2=equals&filter_value_2=Ackerschmalwand&etal=0&filtername=author&filterquery=gnd%2F1184404968&filtertype=authority
IFN-gamma exposes a cryptic cytotoxic T lymphocyte epitope in HIV-1 reverse transcriptase. - Radcliffe Department of MedicineIFN-gamma exposes a cryptic cytotoxic T lymphocyte epitope in HIV-1 reverse transcriptase. - Radcliffe Department of Medicine
The proteasome, an essential component of the ATP-dependent proteolytic pathway in eukaryotic cells, is responsible for the degradation of most cellular proteins and is believed to be the main source of MHC class I-restricted antigenic peptides for presentation to CTL. Inhibition of the proteasome by lactacystin or various peptide aldehydes can result in defective Ag presentation, and the pivotal role of the proteasome in Ag processing has become generally accepted. However, recent reports have challenged this observation. Here we examine the processing requirements of two HLA A*0201-restricted epitopes from HIV-1 reverse transcriptase and find that they are produced by different degradation pathways. Presentation of the C-terminal ILKEPVHGV epitope is impaired in ME275 melanoma cells by treatment with lactacystin, and is independent of expression of the IFN-gamma-inducible proteasome beta subunits LMP2 and LMP7. In contrast, both lactacystin treatment and expression of LMP7 induce the presentation of
https://www.rdm.ox.ac.uk/publications/10404
Bortezomib Followed by the Addition of Doxorubicin at Disease Progression in Treating Patients With Locally Advanced, Recurrent...Bortezomib Followed by the Addition of Doxorubicin at Disease Progression in Treating Patients With Locally Advanced, Recurrent...
OBJECTIVES: Primary I. Determine the objective tumor response in patients with locally advanced, recurrent, or metastatic adenoid cystic carcinoma of the head and neck treated with bortezomib.. Secondary I. Determine the time to progression in patients treated with this drug. II. Determine the overall survival of patients treated with this drug. III. Determine the toxic effects of this drug in these patients. IV. Determine the objective tumor response, time to progression, and overall survival of patients who progress on single-agent bortezomib and are then treated with doxorubicin and bortezomib.. V. Determine the toxic effects of this regimen in these patients. VI. Determine the profile and concentration of inflammatory and angiogenic cytokines in serum of patients before and in response to this regimen.. VII. Correlate the expression of biomarkers which may be affected by the ubiquitin-proteasome degradation pathway (NF-kB, p53, p27, cyclin D1, cyclin E, vascular endothelial growth factor ...
https://clinicaltrials.gov/ct2/show/NCT00077428?cond=%22Adenoid+cystic+carcinoma%22&rank=19
Untersuchungen zur strukturellen und funktionellen Plastizität des 20S-Proteasoms der Maus und seiner Modulierung durch den...Untersuchungen zur strukturellen und funktionellen Plastizität des 20S-Proteasoms der Maus und seiner Modulierung durch den...
The 20S proteasome is the proteolytic core complex of the main cytoplasmic and nuclear protein degradation system. One of the numerous functions assigned to the 20S proteasome is the generation of antigenic peptides from intracellular proteins. MHC class I surface presentation of antigenic peptides is one key event of the cellular immune response. The presented study was aimed on the biochemical and molecular-biological analysis of the 20S proteasome and its activation by regulatory proteins of the PA28 family. In the brain, microglial cells are the major antigen presenting cells and they respond sensitive to pathologic events. Cultured mouse microglia was used as a model to study the correlation between microglial activation parameters and structural plasticity of the 20S/26S proteasome. In response to interferon-g , constitutive active site subunits were replaced by inducible subunits as described for other cellular systems. These replacements result in altered proteolytic cleavage ...
https://edoc.hu-berlin.de/handle/18452/14370
Age-related decrease in proteasome expression contributes to defective nuclear factor-κB activation during hepatic ischemia...Age-related decrease in proteasome expression contributes to defective nuclear factor-κB activation during hepatic ischemia...
Huber, N., Sakai, N., Eismann, T., Shin, T., Kuboki, S., Blanchard, J., Schuster, R., Edwards, M. J., Wong, H. R. and Lentsch, A. B. (2009), Age-related decrease in proteasome expression contributes to defective nuclear factor-κB activation during hepatic ischemia/reperfusion. Hepatology, 49: 1718-1728. doi: 10.1002/hep.22840 ...
http://onlinelibrary.wiley.com/doi/10.1002/hep.22840/references
Julia KelliherJulia Kelliher
Julia is the research technician/lab manager of the Laboratory of Addiction Genetics. She obtained her Bachelor of Arts degree in neurobiology at Boston University and minored in visual arts. At Boston University, Julia worked in Dr. Heng-ye Mans laboratory studying the trafficking and degradation of AMPA receptors to help elucidate the mechanism of the ubiquitin-proteasome degradation pathway. Since joining Dr. Bryants lab, Julia has been researching the genetic basis of binge eating and drug addiction using a systems genetic approach. Specifically, Julia has been working on fine-mapping a region of distal chromosome 1 implicated in sensitivity to oxycodone in a reduced complexity cross in order to identify candidate genes underlying this behavioral addiction trait. Additionally, Julia has been using inbred mouse strains to characterize genetic differences in the behavioral organization of binge eating, conditioned food reward, and compulsive-like eating. Outside of the lab, Julia enjoys ...
http://sites.bu.edu/bryantlab/people/research-technician/julia-kelliher/
Negative feedback loop in the Bim-caspase-3 axis regulating apoptosis and activity of osteoclasts<...
TY - JOUR. T1 - Negative feedback loop in the Bim-caspase-3 axis regulating apoptosis and activity of osteoclasts. AU - Wakeyama, Hidetoshi. AU - Akiyama, Toru. AU - Takahashi, Katsuhiko. AU - Amano, Hitoshi. AU - Kadono, Yuho. AU - Nakamura, Masaki. AU - Oshima, Yasushi. AU - Itabe, Hiroyuki. AU - Nakayama, Keiichi I.. AU - Nakayama, Keiko. AU - Nakamura, Kozo. AU - Tanaka, Sakae. PY - 2007/10. Y1 - 2007/10. N2 - Proapoptotic Bcl-2 family member Bim plays an essential role in the osteoclast apoptosis and is degraded through ubiquitin/proteasome pathways in a caspase-3-dependent manner. This negative feedback loop in the Bim-caspase-3 axis is important for regulating the survival and activity of osteoclasts. Introduction: Bim is a member of the proapoptotic Bcl-2 family and regulates the mitochondrial apoptosis pathway. Bim expression is post-translationally regulated in osteoclasts (OCs) through ubiquitin/proteasome pathways, and Bim is critical for their survival and activity. Materials and ...
https://kyushu-u.pure.elsevier.com/en/publications/negative-feedback-loop-in-the-bim-caspase-3-axis-regulating-apopt
Structural basis for dynamic regulation of the human 26S proteasome | PNASStructural basis for dynamic regulation of the human 26S proteasome | PNAS
The coexistence of four conformational states, one of which is open in its CP gate under common solution conditions, provides insights into the dynamic regulation of the proteasome holoenzyme (Fig. 5H). We may assume SA, the most populated state, to represent a ground state, whereas SD, the state most distinct from SA, to represent the translocating or fully engaged state of the proteasome, in accordance with prior studies of the yeast proteasome (7, 25⇓⇓-28) (SI Appendix, Fig. S8 E and F). By structural criteria (SI Appendix, Table S3), the SB and SC states may represent intermediates between SA and SD, and may describe a progression of conformational transitions that is temporally ordered: SA is converted to SB, then to SC and SD (Fig. 5H). These transitions, although apparently inherent to the proteasome, are expected to be guided by interactions with substrate, particularly the engagement of substrate by the AAA pore loops. The transition from SA to SB involves local dissociation of the ...
https://www.pnas.org/content/113/46/12991?ijkey=1abfcc3f7f4ad9fd4482634662a37147fd5947c5&keytype2=tf_ipsecsha
BSc2118 | CAS#863924-64-5 | Proteasome inhibitor | MedKoo BiosciencesBSc2118 | CAS#863924-64-5 | Proteasome inhibitor | MedKoo Biosciences
BSc2118 is a potent proteasome inhibitor. BSc2118 shows significant antimyeloma activity and may be considered as a promising agent in cancer drug development. BSc2118 is also a promising new candidate for stroke therapy, which may in addition alleviate recombinant tissue-plasminogen activator-induced brain toxicity.
http://www.medkoo.com/products/6063
Proteasome subunits differentially control myeloma cell viability and proteasome inhibitor sensitivity - Fingerprint -...
Fingerprint Dive into the research topics of Proteasome subunits differentially control myeloma cell viability and proteasome inhibitor sensitivity. Together they form a unique fingerprint. ...
https://mayoclinic.pure.elsevier.com/en/publications/proteasome-subunits-differentially-control-myeloma-cell-viability/fingerprints/
Proteases in MHC Class I Presentation and Cross-Presentation | The Journal of ImmunologyProteases in MHC Class I Presentation and Cross-Presentation | The Journal of Immunology
The strongest evidence that the proteasome plays a major role in the generation of most presented peptides comes from studies using highly specific inhibitors of the proteasomes threonine-active sites. In living cells, these agents block completely the presentation of peptides from Ags that require proteolysis, but have no effect on ones that do not need cleavage (e.g., when epitopes are expressed directly from minigenes) and markedly limit the overall supply of peptides to MHC class I molecules (6).. Whereas the immune system has used this phylogentically older pathway for a source of peptides, it also evolved modifications that are thought to play a special role in Ag presentation. One modification is an alternate set of active site subunits (B1i/MHC-linked low molecular weight protein 2, B2i/multicatalytic endopeptidase complex-like 1, B5i/MHC-linked low molecular weight protein 7) that, when expressed preferentially, incorporate into newly assembling proteasomes in place of the standard ...
http://www.jimmunol.org/content/184/1/9
IJMS | Free Full-Text | Chaperones and the Proteasome System: Regulating the Construction and Demolition of Striated MuscleIJMS | Free Full-Text | Chaperones and the Proteasome System: Regulating the Construction and Demolition of Striated Muscle
Protein folding factors (chaperones) are required for many diverse cellular functions. In striated muscle, chaperones are required for contractile protein function, as well as the larger scale assembly of the basic unit of muscle, the sarcomere. The sarcomere is complex and composed of hundreds of proteins and the number of proteins and processes recognized to be regulated by chaperones has increased dramatically over the past decade. Research in the past ten years has begun to discover and characterize the chaperones involved in the assembly of the sarcomere at a rapid rate. Because of the dynamic nature of muscle, wear and tear damage is inevitable. Several systems, including chaperones and the ubiquitin proteasome system (UPS), have evolved to regulate protein turnover. Much of our knowledge of muscle development focuses on the formation of the sarcomere but recent work has begun to elucidate the requirement and role of chaperones and the UPS in sarcomere maintenance and disease. This review will
https://www.mdpi.com/1422-0067/19/1/32
Proteasome Inhibitors: A Novel Class of Potent and Effective Antitumor Agents | Cancer ResearchProteasome Inhibitors: A Novel Class of Potent and Effective Antitumor Agents | Cancer Research
The fundamental goal of many chemotherapeutic agents currently used to treat neoplastic disease is to interfere with tumor cell metabolism and the mitotic process by blocking protein and DNA synthesis. This report describes a novel series of very selective inhibitors of the proteasome that serve to block cellular protein degradation. Although protein turnover is required for normal cell function, there is much data linking protein turnover to cell cycle regulation (3) . As such, these data support a causal relationship between inhibition of the proteasome and inhibition of cell growth in human tumor cell lines in vitro. The structure-activity relationship determined here correlates very well to tumor cell growth inhibition and provided strong support that the inhibition of the biochemical target, the proteasome, was directly related to the biological effect of the compounds. Moreover, the in vitro data suggest that the proteasome has a significant role in maintaining cell viability and ...
https://cancerres.aacrjournals.org/content/59/11/2615?ijkey=d0d9ea568bb115718bb98a9851afa4af64f7a396&keytype2=tf_ipsecsha
A d-Amino Acid at the N-Terminus of a Protein Abrogates Its Degradation by the N-End Rule PathwayA d-Amino Acid at the N-Terminus of a Protein Abrogates Its Degradation by the N-End Rule Pathway
Eukaryotes have evolved the ubiquitin (Ub)/proteasome system to degrade polypeptides. The Ub/proteasome system is one way that cells regulate cytosolic protein and amino acids levels through the recognition and ubiquitination of a proteins N-terminus via E1, E2, and E3 enzymes. The process by which the N-terminus stimulates intracellular protein degradation is referred to as the N-end rule. Characterization of the N-end rule has been limited to only the natural l-amino acids. Using a cytosolic delivery platform derived from anthrax lethal toxin, we probed the stability of mixed chirality proteins, containing one d-amino acid on the N-terminus of otherwise all l-proteins. In all cases, we observed that one N-terminal d-amino acid stabilized the cargo protein to proteasomal degradation with respect to the N-end rule. We found that since the mixed chirality proteins were not polyubiquitinated, they evaded N-end-mediated proteasomal degradation. Evidently, a subtle change on the N-terminus of a ...
http://dspace.mit.edu/handle/1721.1/110605
Abstract WP394: The Proteasome Subunit α Type 6 Rs1048990 Contributes To The Risk Of Ischemic Stroke And Its Subtypes: New Data...Abstract WP394: The Proteasome Subunit α Type 6 Rs1048990 Contributes To The Risk Of Ischemic Stroke And Its Subtypes: New Data...
Background and purpose: The proteasome subunit α type 6 (PSMA6) is an important proteolytic protein regulating the expression of genes involved in inflammation. Recently, a functional polymorphism rs1048990, located in PSMA6, has been reported with the susceptibility to ischemic stroke (IS) in several ethnic cohorts, but the results were inconsistent. Moreover, it still lacks the data in Asian. The purpose of the present study was to determine whether this polymorphism confers significant risk to IS in a Chinese population.. Methods: A total of 1102 IS cases and 975 healthy controls were analyzed in our study. We genotyped rs1048990 with ligation detection reaction (LDR) method and then performed a meta-analysis.. Results: Significant association between rs1048990 in PSMA6 and ischemic stroke was observed in all comparison models (genotype, p=0.016; allele, p=0.004; CG+GG vs. CC, adjusted p=0.006; GG vs. CG+CC, adjusted p=0.038). Further stratification for stroke subtype, similar differences ...
http://stroke.ahajournals.org/content/47/Suppl_1/AWP394
Tripterin (Celastrol) | Proteasome Inhibitor | MedChemExpressTripterin (Celastrol) | Proteasome Inhibitor | MedChemExpress
Tripterin (Celastrol) is a proteasome inhibitor which potently and preferentially inhibits the chymotrypsin-like activity of a purified 20S proteasome with IC50 of 2.5 μM. - Mechanism of Action & Protocol.
https://www.medchemexpress.com/Celastrol.html
The Use of RNA Polymerase II Antibodies In Proteasome Regulation Studies | Antibody News: Novus BiologicalsThe Use of RNA Polymerase II Antibodies In Proteasome Regulation Studies | Antibody News: Novus Biologicals
At Novus Biologicals, we recently added a new RNA Polymerase II antibody (clone 4H8) to our antibody catalog. RNAPII is an essential transcription enzyme,
https://www.novusbio.com/antibody-news/antibodies/the-use-of-rna-polymerase-ii-antibodies-in-proteasome-regulation-studies
PYR-41 | ≥99%(HPLC) | Selleck | E1 Activating inhibitor ...PYR-41 | ≥99%(HPLC) | Selleck | E1 Activating inhibitor ...
PYR-41 (50 μM) inhibits activity of ubiquitin-activating enzyme E1 by over 90%. PYR-41 could be a target for nucleophilic attack and potentially reacts with the active site cysteine of E1. PYR-41 efficiently blocks cyclin E degradation. PYR-41 decreases the level of E1fUb thioesters in cells with a IC50 of between 10 and 25 μM, and prevents proteasome inhibitor-induced accumulation of ubiquitylated proteins. PYR-41 increases total sumoylation in cells and in cell harboring temperature-sensitive E1. PYR-41 is able to inhibit both proteasome-dependent and proteasome-independent activities of ubiquitylation. PYR-41 (50 μM) attenuates 1 ng/mL IL-1α-mediated nuclear factor-κB activation by >60% through preventing the downstream ubiquitylation and proteasomal degradation of IκBα. PYR-41 inhibits degradation of p53 and activates the transcriptional activity of p53, which enable its differentially killing transformed p53-expressing cells. [1] PYR-41 blocks ubiquitination reactions but ...
https://www.selleckchem.com/products/pyr-41.html
Proteasome endopeptidase complexProteasome endopeptidase complex
... (EC 3.4.25.1, ingensin, macropain, multicatalytic endopeptidase complex, prosome, ... Proteasome+endopeptidase+complex at the US National Library of Medicine Medical Subject Headings (MeSH) Portal: Biology ( ... multicatalytic proteinase (complex), MCP, proteasome, large multicatalytic protease, proteasome organelle, alkaline protease, ... Groll M, Ditzel L, Löwe J, Stock D, Bochtler M, Bartunik HD, Huber R (April 1997). "Structure of 20S proteasome from yeast at ...
https://en.wikipedia.org/wiki/Proteasome_endopeptidase_complex
ProteasomeProteasome
"Evidence that pituitary cation-sensitive neutral endopeptidase is a multicatalytic protease complex". Journal of Neurochemistry ... The assembly of the proteasome is a complex process due to the number of subunits that must associate to form an active complex ... Proteasome subunit nomenclature guide 3D proteasome structures in the EM Data Bank(EMDB) Key points of proteasome function ( ... "The 1.9 A structure of a proteasome-11S activator complex and implications for proteasome-PAN/PA700 interactions". Molecular ...
https://en.wikipedia.org/wiki/Proteasome
List of EC numbers (EC 3)List of EC numbers (EC 3)
ADAM 17 endopeptidase EC 3.4.24.87: ADAMTS13 endopeptidase EC 3.4.25.1: proteasome endopeptidase complex EC 3.4.25.2: HslU-HslV ... ADAM 17 endopeptidase EC 3.4.24.87: ADAMTS13 endopeptidase EC 3.4.25.1: proteasome endopeptidase complex EC 3.4.25.2: HslU-HslV ... multicatalytic endopeptidase complex. Now EC 3.4.25.1, proteasome endopeptidase complex EC 3.5.1.1: asparaginase EC 3.5.1.2: ... multicatalytic endopeptidase complex. Now EC 3.4.25.1, proteasome endopeptidase complex EC 3.5.1.1: asparaginase EC 3.5.1.2: ...
https://en.wikipedia.org/wiki/List_of_EC_numbers_(EC_3)
MCPMCP
... a form of pectin Proteasome endopeptidase complex, an enzyme Metoclopramide, a medication to treat nausea and other problems ...
https://en.wikipedia.org/wiki/MCP
PSMAPSMA
... a human enzyme Proteasome endopeptidase complex subunits: PSMA1 PSMA2 PSMA3 PSMA4 PSMA5 PSMA6 PSMA7 PSMA8 This disambiguation ...
https://en.wikipedia.org/wiki/PSMA
List of MeSH codes (D05)List of MeSH codes (D05)
... photosystem ii protein complex MeSH D05.500.562.500 - proteasome endopeptidase complex MeSH D05.500.562.625 - pyruvate ... electron transport complex i MeSH D05.500.562.374 - electron transport complex iv MeSH D05.500.562.437 - fatty acid synthetase ... electron transport complex iii MeSH D05.500.562.875 - sucrase-isomaltase complex MeSH D05.750.078.139 - chitin MeSH D05.750. ... MeSH D05.500.249.600 - phycobilisomes MeSH D05.500.562.124 - cytochrome b6f complex MeSH D05.500.562.124.500 - plastoquinol- ...
https://en.wikipedia.org/wiki/List_of_MeSH_codes_(D05)
List of MeSH codes (D08)List of MeSH codes (D08)
... proteasome endopeptidase complex MeSH D08.811.600.741 - pyruvate dehydrogenase complex MeSH D08.811.600.741.525 - ... proteasome endopeptidase complex MeSH D08.811.277.913.292 - arginase MeSH D08.811.399.325.500 - peptidylprolyl isomerase MeSH ... electron transport complex i MeSH D08.811.600.250.500.750 - electron transport complex ii MeSH D08.811.600.250.500.750.500 - ... endopeptidase clp MeSH D08.811.277.656.149.500 - protease la MeSH D08.811.277.656.300 - endopeptidases MeSH D08.811.277.656. ...
https://en.wikipedia.org/wiki/List_of_MeSH_codes_(D08)
Endopeptidase ClpEndopeptidase Clp
... a heat shock protein complex thought to resemble the hypothetical ancestor of the proteasome. The Hsp100 family of eukaryotic ... Endopeptidase Clp (EC 3.4.21.92, endopeptidase Ti, caseinolytic protease, protease Ti, ATP-dependent Clp protease, ClpP, Clp ... Endopeptidase+Clp at the US National Library of Medicine Medical Subject Headings (MeSH) Portal: Biology (Protein pages needing ... Endopeptidase CLP protease family ATP-dependent Clp protease proteolytic subunit Gottesman S, Clark WP, Maurizi MR (May 1990 ...
https://en.wikipedia.org/wiki/Endopeptidase_Clp
PSMB10PSMB10
"Constitutive and interferon-gamma-induced expression of the human proteasome subunit multicatalytic endopeptidase complex-like ... These regulatory particles include 19S proteasome complexes, 11S proteasome complex, etc. Following the CP-RP association, the ... The resulting proteasome complex becomes the so-called immunoproteasome. An essential function of the modified proteasome ... that contributes to the complete assembly of 20S proteasome complex. In particular, proteasome subunit beta-2i, along with ...
https://en.wikipedia.org/wiki/PSMB10
OligopeptidaseOligopeptidase
... proteasomes, cathepsins among many others. The prolyl-oligopeptidase or prolyl endopeptidase (POP) is a good example of how an ... proteolysis of intracellular or extracellular protein precursors performed by several processing enzymes or protease complexes ... Oligopeptidase is a term coined in 1979 to designate a sub-group of the endopeptidases, which are not involved in the digestion ... 1997). "Targeting of endopeptidase 24.16 to different subcellular compartments by alternative promoter usage". J Biol Chem. 272 ...
https://en.wikipedia.org/wiki/Oligopeptidase
THOP1THOP1
1997). "Human endopeptidase (THOP1) is localized on chromosome 19 within the linkage region for the late-onset alzheimer ... 2001). "Major histocompatibility complex class I-presented antigenic peptides are degraded in cytosolic extracts primarily by ... Saric T, Graef CI, Goldberg AL (2004). "Pathway for degradation of peptides generated by proteasomes: a key role for thimet ... 2003). "The cytosolic endopeptidase, thimet oligopeptidase, destroys antigenic peptides and limits the extent of MHC class I ...
https://en.wikipedia.org/wiki/THOP1
Thimet oligopeptidaseThimet oligopeptidase
... a review of a thiol dependent metallo-endopeptidase also known as Pz-peptidase endopeptidase 24.15 and endo-oligopeptidase". ... In plants, specifically in A. thaliana, the enzymes were more recently discovered as part of the 20S proteasome and SA-binding ... The enzyme substrate complex is maintained by several non-covalent interactions: hydrophobic and polar interactions. The ... and endopeptidase 24.15. In 1992 the name "thimet oligopeptidases" was proposed by the International Union of Biochemistry and ...
https://en.wikipedia.org/wiki/Thimet_oligopeptidase
ProteaseProtease
... the membrane associated LonB protease and a soluble 20S proteosome complex . The field of protease research is enormous. Since ... endopeptidases, such as trypsin, chymotrypsin, pepsin, papain, elastase). Catalysis is achieved by one of two mechanisms: ... By a complex cooperative action, proteases can catalyze cascade reactions, which result in rapid and efficient amplification of ... Bacteria contain proteases responsible for general protein quality control (e.g. the AAA+ proteasome) by degrading unfolded or ...
https://en.wikipedia.org/wiki/Protease
RicinRicin
The propolypeptide is cleaved within protein bodies by an endopeptidase to produce the mature ricin protein that is composed of ... ERAD normally removes misfolded ER proteins to the cytosol for their destruction by cytosolic proteasomes. Dislocation of RTA ... Ricin B chain binds complex carbohydrates on the surface of eukaryotic cells containing either terminal N-acetylgalactosamine ... of the proteasome itself, that results in its folding to a catalytic conformation, which de-purinates ribosomes, thus halting ...
https://en.wikipedia.org/wiki/Ricin
PBDC1PBDC1
Pepsin (pH 1.3), Asp-N endopeptidase, N-terminal Glutamate and Proteinase K all had 50 or more cleavage sites within the ... CLDN1 is a major component in forming tight junction complexes between cells, which foster cell-cell adhesion of cell membranes ... For example, ubiquitiation and subsequent degradation of the 26S proteasome serves an important function in regulating ... March 2006). "Global landscape of protein complexes in the yeast Saccharomyces cerevisiae". Nature. 440 (7084): 637-43. Bibcode ...
https://en.wikipedia.org/wiki/PBDC1
3C-like protease3C-like protease
The X-ray structures of the unliganded SARS-CoV-2 protease 3CLpro and its complex with an α-ketoamide inhibitor provides a ... The 3C-like protease (3CLpro) or main protease (Mpro), formally known as C30 endopeptidase or 3-chymotrypsin-like protease, is ... July 2019). "Synthesis and Biological Activity of Peptide α-Ketoamide Derivatives as Proteasome Inhibitors". ACS Medicinal ... is essential for the activity of the SARS-coronavirus replication-transcription complex". Virology. 484: 313-22. doi:10.1016/j. ...
https://en.wikipedia.org/wiki/3C-like_protease
Death regulator Nedd2-like caspaseDeath regulator Nedd2-like caspase
This complex is called the apoptosome. Dark, just as Apaf-1, has an N-terminal CARD domain that interacts with caspase Dronc, ... The main function of this kind of endopeptidases is to catalyze the hydrolysis of peptide bonds in order to cleave proteins ... "The initiator caspase Dronc is subject of enhanced autophagy upon proteasome impairment in Drosophila". Cell Death and ... In humans, initiator caspases such as Caspase-2 and Caspase-9 have a prodomain that cleaves caspases to a holoenzyme complex in ...
https://en.wikipedia.org/wiki/Death_regulator_Nedd2-like_caspase
Research Profile Listing | Yale School of MedicineResearch Profile Listing | Yale School of Medicine
Proteasome Endopeptidase Complex. *. Craig Crews, PhD. John C. Malone Professor of Molecular, Cellular, and Developmental ...
https://medicine.yale.edu/research-profiles/?orgId=113592&meshId=22423
The proteasome is an integral part of solar ultraviolet a radiation-induced gene expressionThe proteasome is an integral part of solar ultraviolet a radiation-induced gene expression
Proteasome Endopeptidase Complex / genetics* * Signal Transduction * Skin / cytology * Skin / radiation effects * Stress, ... The proteasome is an integral part of solar ultraviolet a radiation-induced gene expression J Biol Chem. 2009 Oct 30;284(44): ... In the present study we identify the proteasome as an integral part of the UVA-induced, intracellular signaling cascade in ... Increased transcription factor activation was also observed if the proteasome was inhibited by cross-linked proteins or ...
https://pubmed.ncbi.nlm.nih.gov/19690165/
Biblio | Page 3 | Linus Pauling Institute | Oregon State UniversityBiblio | Page 3 | Linus Pauling Institute | Oregon State University
Proteasome Endopeptidase Complex. Pride H, Yu Z, Sunchu B, Mochnick J, Coles A, Zhang Y, Buffenstein R, Hornsby PJ, Austad SN, ...
https://lpi.oregonstate.edu/biblio?f%5Bauthor%5D=4206&o=desc&page=2&s=keyword
PSMB8 gene: MedlinePlus GeneticsPSMB8 gene: MedlinePlus Genetics
multicatalytic endopeptidase complex subunit C13. *NKJO. *protease component C13. *proteasome (prosome, macropain) subunit, ... Immunoproteasomes are specialized versions of proteasomes, which are large complexes that recognize and break down (degrade) ... Proteasome assembly defect due to a proteasome subunit beta type 8 (PSMB8) mutation causes the autoinflammatory disorder, ... While proteasomes are found in many types of cells, immunoproteasomes are located primarily in immune system cells. These ...
https://medlineplus.gov/genetics/gene/psmb8/
Dendritic cell maturation enhances CD8+ T-cell responses to exogenous antigen via a proteasome-independent mechanism of major...
... enhances CD8+ T-cell responses to exogenous antigen via a proteasome-independent mechanism of major histocompatibility complex ... enhances CD8+ T-cell responses to exogenous antigen via a proteasome-independent mechanism of major histocompatibility complex ... Major Histocompatibility Complex 97% * Ovalbumin 45% * Proteasome Endopeptidase Complex 100% * Quil A 24% ...
https://www.research.ed.ac.uk/en/publications/dendritic-cell-maturation-enhances-cd8-t-cell-responses-to-exogen/fingerprints/?sortBy=alphabetically
Tomoyoshi Kondos Research | CureHunterTomoyoshi Kondo's Research | CureHunter
Proteasome Endopeptidase Complex (Proteasome)IBA 05/2005. 1. Heme Oxygenase-1IBA 05/2005. ...
https://www.curehunter.com/public/authorSummary-Kondo,%20Tomoyoshi.do
CN103524509B - The salt of Zhan Nasi kinase inhibitor (R)-3-(4-(7H-pyrrolo-[2,3-d] pyrimidine-4-yl)-1H-pyrazol-1-yl)-3...
102000004245 Proteasome Endopeptidase Complex Human genes 0.000 description 1 * 108090000708 Proteasome Endopeptidase Complex ...
https://patents.google.com/patent/CN103524509B/en
Keith L Knutson - Research output - Mayo Clinic
Proteasome Endopeptidase Complex 76% * Breast Neoplasms 58% * T-Lymphocytes 56% 10 Scopus citations ... Analysis of complex biomarkers for human immune-mediated disorders based on cytokine responsiveness of peripheral blood cells. ... D3-induced myeloid cell differentiation is regulated by a vitamin D receptor-phosphatidylinositol 3-kinase signaling complex. ...
https://mayoclinic.pure.elsevier.com/en/persons/keith-l-knutson/publications/?type=%2Fdk%2Fatira%2Fpure%2Fresearchoutput%2Fresearchoutputtypes%2Fcontributiontojournal%2Farticle&ordering=type&descending=false
Targeting Ca2 + Signals in intact native smooth muscle cells - University of StrathclydeTargeting Ca2 + Signals in intact native smooth muscle cells - University of Strathclyde
RPGR protein complex regulates proteasome activity and mediates store-operated calcium entry. Patnaik, S. R., Zhang, X., Biswas ...
https://pureportal.strath.ac.uk/en/projects/targeting-ca2-signals-in-intact-native-smooth-muscle-cells
proteasome 20S subunit beta 1 | T1: Proteasome | IUPHAR/BPS Guide to PHARMACOLOGYproteasome 20S subunit beta 1 | T1: Proteasome | IUPHAR/BPS Guide to PHARMACOLOGY
Proteasome. Detailed annotation on the structure, function, physiology, pharmacology and clinical relevance of drug targets. ... proteasome gamma chain , proteasome subunit C5 , multicatalytic endopeptidase complex subunit C5 , proteasome (prosome, ... macropain) subunit, beta type 1 , proteasome (prosome, macropain) subunit, beta type, 1 , proteasome (prosome , proteasome ... T1: Proteasome: proteasome 20S subunit beta 1. Last modified on 12/09/2019. Accessed on 09/12/2022. IUPHAR/BPS Guide to ...
https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2404&familyId=752&familyType=ENZYME
A partnership with the proteasome: the destructive nature of GSK3 - Projects - Discovery - the University of Dundee...
Proteasome Endopeptidase Complex 38% * Carrier Proteins 31% Powered by Pure, Scopus & Elsevier Fingerprint Engine™ © 2022 ... A partnership with the proteasome: the destructive nature of GSK3. Holly Robertson, John D. Hayes, Calum Sutherland (Lead / ...
https://discovery.dundee.ac.uk/en/publications/a-partnership-with-the-proteasome-the-destructive-nature-of-gsk3/projects/?ordering=endDate&descending=true
Muscle atrophy, ubiquitin-proteasome, and autophagic pathways in dysferlinopathy<...
Proteasome Endopeptidase Complex Medicine & Life Sciences 60% * Ubiquitin Medicine & Life Sciences 58% ... Muscle atrophy, ubiquitin-proteasome, and autophagic pathways in dysferlinopathy. In: Muscle and Nerve. 2014 ; Vol. 50, No. 3. ... Muscle atrophy, ubiquitin-proteasome, and autophagic pathways in dysferlinopathy. Marina Fanin, Anna C. Nascimbeni, Corrado ... Muscle atrophy, ubiquitin-proteasome, and autophagic pathways in dysferlinopathy. / Fanin, Marina; Nascimbeni, Anna C.; ...
https://moh-it.pure.elsevier.com/en/publications/muscle-atrophy-ubiquitin-proteasome-and-autophagic-pathways-in-dy
NEW (2008) DeCS DESCRIPTORS WITH SCOPE NOTES (UNIT RECORD FORMAT; 21/02/2008NEW (2008) DeCS DESCRIPTORS WITH SCOPE NOTES (UNIT RECORD FORMAT; 21/02/2008
... ligase complexes to label proteins for transport to the PROTEASOME ENDOPEPTIDASE COMPLEX where proteolysis occurs. HN - 2008 MH ... Many of the proteins in this class are recruited to specific cellular targets such as a cell surface receptor complexes via ... HN - 2008 MH - Fatty Acid Synthetase Complex, Type II UI - D054889 MN - D05.500.562.437.500 MN - D08.811.600.317.500 MS - The ... HN - 2008; use BETA-N-ACETYLHEXOSAMINIDASES 1987-2007 BX - Hex B MH - Fatty Acid Synthetase Complex, Type I UI - D054890 MN - ...
https://decs.bvs.br/I/dcsnew2008.txt
Human T-cell leukemia virus type 1 Tax protein binds to assembled nuclear proteasomes and enhances their proteolytic activity. ...
Tax mutants revealed that both the Tax N and C termini play a role in proteasome binding. We also found that proteasomes from ... This effect was not due to the induction of the LMP2 and LMP7 proteasome subunits. Furthermore, Tax appeared to be a long-lived ... We found that Tax bound to assembled nuclear proteasomes, but Tax could not be detected in the cytoplasm. Confocal microscopy ... this process probably takes place prior to and independent of proteasome association. ...
https://www.ndph.ox.ac.uk/publications/31965
Metabolism and mis-metabolism of the neuropathological signature protein TDP-43 - Fingerprint - Taipei Medical University
Proteasome Endopeptidase Complex 19% * Ubiquitin 19% * Neurodegenerative Diseases 16% * Cultured Cells 16% ...
https://tmu.pure.elsevier.com/en/publications/metabolism-and-mis-metabolism-of-the-neuropathological-signature-/fingerprints/
Biomedicina, Neuroscienze e Diagnostica avanzata - Research output - Università degli Studi di Palermo - Research Portal
Widespread, but non-identical, association of proteasomal 19 and 20 S proteins with yeast chromatin<...
Proteasome Endopeptidase Complex Medicine & Life Sciences 62% * Pharmacological Metabolism Chemical Compounds 61% ... Although the data support the presence of the intact 26 S proteasome on most genes, several hundred yeast genes were cross- ... Although the data support the presence of the intact 26 S proteasome on most genes, several hundred yeast genes were cross- ... Although the data support the presence of the intact 26 S proteasome on most genes, several hundred yeast genes were cross- ...
https://asu.pure.elsevier.com/en/publications/widespread-but-non-identical-association-of-proteasomal-19-and-20
Overweight condition and waist circumference and a candidate gene within the 12q24 locus<...
Proteasome Endopeptidase Complex Medicine & Life Sciences 59% * Noninsulin-Dependent Diabetes Mellitus 2 Medicine & Life ... The gene of proteasome modulator 9 (PSMD9) lies in the NIDDM2 region and is linked to type 2 diabetes (T2D), microvascular and ... The gene of proteasome modulator 9 (PSMD9) lies in the NIDDM2 region and is linked to type 2 diabetes (T2D), microvascular and ... The gene of proteasome modulator 9 (PSMD9) lies in the NIDDM2 region and is linked to type 2 diabetes (T2D), microvascular and ...
https://creighton.pure.elsevier.com/en/publications/overweight-condition-and-waist-circumference-and-a-candidate-gene
Plasmodium falciparum: The fungal metabolite gliotoxin inhibits proteasome proteolytic activity and exerts a plasmodicidal...
proteasome endopeptidase complex 69% * metabolites 39% * chloroquine 22% * antimalarials 20% * hepatocytes 15% ... Dive into the research topics of Plasmodium falciparum: The fungal metabolite gliotoxin inhibits proteasome proteolytic ... Plasmodium falciparum: The fungal metabolite gliotoxin inhibits proteasome proteolytic activity and exerts a plasmodicidal ...
https://okayama.pure.elsevier.com/en/publications/plasmodium-falciparum-the-fungal-metabolite-gliotoxin-inhibits-pr/fingerprints/
FBXO15 regulates P-glycoprotein/ABCB1 expression through the ubiquitin-proteasome pathway in cancer cells - Fingerprint -...
Proteasome Endopeptidase Complex 95% * Ubiquitin 91% * Ubiquitination 36% * Neoplasms 29% * Drug Resistance 10% ... Dive into the research topics of FBXO15 regulates P-glycoprotein/ABCB1 expression through the ubiquitin-proteasome pathway in ... FBXO15 regulates P-glycoprotein/ABCB1 expression through the ubiquitin-proteasome pathway in cancer cells. ...
https://keio.pure.elsevier.com/en/publications/fbxo15-regulates-p-glycoproteinabcb1-expression-through-the-ubiqu/fingerprints/
Internal Medicine - Projects - Research Nebraska
Proteasome Endopeptidase Complex 61% * Liver 51% * Wounds and Injuries 47% * Proteins 39% ... Effects of Ethanol on Proteasome-HCV Core Protein Interactions. Osna, N. A. ...
https://experts.nebraska.edu/en/organisations/internal-medicine/projects/?status=FINISHED
Dennis Koop - Grants - Oregon Health & Science UniversityDennis Koop - Grants - Oregon Health & Science University
proteasome endopeptidase complex 100% * ethanol 80% * toxicity 78% * Ethanol 72% * Alcohols 61% ...
https://ohsu.pure.elsevier.com/en/persons/dennis-koop/projects/
Douglas Mann - Research output - Research Profiles at Washington University School of MedicineDouglas Mann - Research output - Research Profiles at Washington University School of Medicine
Proteasome Endopeptidase Complex 52% * Autophagy 48% 11 Scopus citations * Improvement of ejection fraction and mortality in ...
https://profiles.wustl.edu/en/persons/douglas-mann/publications/?page=2&ordering=type&descending=false
Pharmaceutical Biotechnology and Molecular Biology<...Pharmaceutical Biotechnology and Molecular Biology<...
Proteasome Endopeptidase Complex 100% * Lipopolysaccharides 82% * Substantia Nigra 81% * Inflammation 56% * Parkinson Disease ... C054 - Peripheral LPS-induced inflammation increases the susceptibility for proteasome inhibition-induced degeneration of the ...
https://researchportal.vub.be/en/organisations/pharmaceutical-biotechnology-and-molecular-biology
Time-resolved multi-omics analysis reveals the role of nutrient stress-induced resource reallocation for TAG accumulation in...Time-resolved multi-omics analysis reveals the role of nutrient stress-induced resource reallocation for TAG accumulation in...
Proteases involved in the UPS, such as proteasome complexes and endopeptidase complexes, are also ATP-dependent and are ... 20S proteasome subunit alpha, PSMB, 20S proteasome subunit beta, ltaE, threonine aldolase, BLMH, bleomycin hydrolase, GAD, ... 2e). The 26S proteasome regulatory subunits (RPN; RPN5, RPN7, RPN9, RPN10, RPN11, RPN12, RPN13, PSMA5, PSMB5, and PSMA6), which ... 3b and 5c). Pyruvate kinase 1 (PYK1) and the pyruvate dehydrogenase complex (PDA1), which catalyze the conversion of ...
https://biotechnologyforbiofuels.biomedcentral.com/articles/10.1186/s13068-020-01757-1
DeCSDeCS
Proteasome Endopeptidase Complex Entry term(s). 20S Proteasome Complex, Multicatalytic Endopeptidase Complex, Proteasome ... Proteasome endopeptidase complex Entry term(s):. 20S Proteasome. Complex, Multicatalytic Endopeptidase. Complex, Proteasome ... Endopeptidase Complex, Proteasome Macropain Macroxyproteinase Multicatalytic Endopeptidase Complex Multicatalytic Proteinase ... 2005; PROTEASOME ENDOPEPTIDASE COMPLEX was indexed under CYSTEINE ENDOPEPTIDASES & MULTIENZYME COMPLEXES 1986-2004. ...
https://decs.bvsalud.org/en/ths/resource/?id=38685&filter=ths_exact_term&q=PROTEASOME
Modulatory effects of bortezomib on host immune cell functions<...
Proteasome Inhibitors Medicine & Life Sciences 24% * Proteasome Endopeptidase Complex Medicine & Life Sciences 21% ... Along with inhibiting the proteasome and thus sensitizing tumor cells to apoptosis, bortezomib may also have multiple effects ... Along with inhibiting the proteasome and thus sensitizing tumor cells to apoptosis, bortezomib may also have multiple effects ... Along with inhibiting the proteasome and thus sensitizing tumor cells to apoptosis, bortezomib may also have multiple effects ...
https://augusta.pure.elsevier.com/en/publications/modulatory-effects-of-bortezomib-on-host-immune-cell-functions
Dynamic resolution of functionally related gene sets in response to acute heat stress<...Dynamic resolution of functionally related gene sets in response to acute heat stress<...
Proteasome Endopeptidase Complex Medicine & Life Sciences 31% * Computational Biology Medicine & Life Sciences 28% ... Conclusion: In summary, we show that the transcriptional response to acute cell stress is largely transient and proteosome- ... Conclusion: In summary, we show that the transcriptional response to acute cell stress is largely transient and proteosome- ... Conclusion: In summary, we show that the transcriptional response to acute cell stress is largely transient and proteosome- ...
https://einstein.pure.elsevier.com/en/publications/dynamic-resolution-of-functionally-related-gene-sets-in-response-
The exon 1-8C/G SNP in the PSMA6 gene contributes only a small amount to the burden of myocardial infarction in 6946 cases and...
The proteasome system is a proteolytic pathway that regulates the expression of genes involved in inflammation. Polymorphisms ... Multienzyme Complexes, Myocardial Infarction, Odds Ratio, Polymorphism, Single Nucleotide, Proteasome Endopeptidase Complex, ... The proteasome system is a proteolytic pathway that regulates the expression of genes involved in inflammation. Polymorphisms ...
https://ckbiobank.kairuku.haiku.fry-it.com/publications/96296
IMSEAR at SEARO: Search
ProteinsUbiquitin ligasesSingle NucleotideDegradationInhibitorsPathwayProteolysisProteolytic activityLarge complexesMicroscopySubunitsInhibitionPathwaysChromatinThermoplasmaTumorYeastIntracellularMultisubunitMiceCellsMoleculesInductionMechanismTranscriptional
Proteins9
  • Increased transcription factor activation was also observed if the proteasome was inhibited by cross-linked proteins or lactacystin, indicating a general mechanism. (nih.gov)
  • Immunoproteasomes are specialized versions of proteasomes, which are large complexes that recognize and break down (degrade) unneeded, excess, or abnormal proteins within cells. (medlineplus.gov)
  • They appear to be involved in some of the same fundamental cell activities as regular proteasomes, such as regulating the amount of various proteins in cells (protein homeostasis), cell growth and division, the process by which cells mature to carry out specific functions (differentiation), chemical signaling within cells, and the activity of genes. (medlineplus.gov)
  • A large multisubunit complex that plays an important role in the degradation of most of the cytosolic and nuclear proteins in eukaryotic cells. (bvsalud.org)
  • The complex digests ubiquitinated proteins and protein activated via ornithine decarboxylase antizyme. (bvsalud.org)
  • Ubiquitin modification of ER associated cellular and viral proteins, alongside the actions of the 26S proteasome, are vital for the regulation of infection. (tamu.edu)
  • Such targets include necessary modification of viral proteins which may stabilize certain complexes, or modification of Argonaute to suppress gene silencing. (tamu.edu)
  • Manipulation of the ubiquitin-proteasome system to achieve targeted degradation of proteins within cells using chemical tools and drugs has the potential to transform pharmacological and therapeutic approaches in cancer and other diseases. (icr.ac.uk)
  • In this review, we survey recent breakthroughs achieved in these two complementary methods and the discovery of new modes of direct and indirect engagement of target proteins with the proteasome. (icr.ac.uk)
Ubiquitin ligases1
  • Viruses can arrogate ER associated ubiquitination as well as cytosolic ubiquitin ligases with the purpose of directing the ubiquitin proteasome system (UPS) to new targets. (tamu.edu)
Single Nucleotide1
  • The gene of proteasome modulator 9 (PSMD9) lies in the NIDDM2 region and is linked to type 2 diabetes (T2D), microvascular and macrovascular complications of T2D.We aimed at studying whether the PSMD9 T2D risk single nucleotide polymorphisms (SNPs) IVS3+nt460, IVS3+nt437, and 197G are linked to obesity, overweight status and waist circumference in Italian T2D families.Methods and results: We screened 200 Italians T2D siblings/families for PSMD9 variants. (elsevier.com)
Degradation4
  • These data suggest that the association of Tax with the proteasome and the enhanced proteolytic activity do not target Tax for rapid degradation and may not determine its immunodominance. (ox.ac.uk)
  • Chemical approaches to targeted protein degradation through modulation of the ubiquitin-proteasome pathway. (icr.ac.uk)
  • In parallel, the development of larger bifunctional molecules that bring together highly specific protein targets in complexes with CRBN, von Hippel-Lindau, or other E3 ligases to promote ubiquitin-dependent degradation has progressed to generate selective chemical compounds with potent effects in cells and in vivo models, providing valuable tools for biological target validation and with future potential for therapeutic use. (icr.ac.uk)
  • TRIM25 increased p53 and Mdm2 abundance by inhibiting their ubiquitination and degradation in 26 S proteasomes. (ox.ac.uk)
Inhibitors1
  • 2014) Optimization of peptidomimetic boronates bearing a P3 bicyclic scaffold as proteasome inhibitors. (guidetopharmacology.org)
Pathway3
  • It has recently become clear that various aspects of nucleic acid metabolism and the ubiquitin-proteasome pathway intersect in several direct and important ways. (elsevier.com)
  • Bortezomib is an inhibitor of the ubiquitin-proteasome proteolytic pathway responsible for intracellular protein turnover. (elsevier.com)
  • The proteasome system is a proteolytic pathway that regulates the expression of genes involved in inflammation. (fry-it.com)
Proteolysis1
  • Protein turnover-related pathways were significantly affected including protein folding, pre-mRNA processing, mRNA splicing, proteolysis and proteasome-related pathways. (elsevier.com)
Proteolytic activity2
  • Human T-cell leukemia virus type 1 Tax protein binds to assembled nuclear proteasomes and enhances their proteolytic activity. (ox.ac.uk)
  • We also found that proteasomes from Tax-transfected cells had enhanced proteolytic activity on prototypic peptide substrates. (ox.ac.uk)
Large complexes1
  • NGL viewer: web-based molecular graphics for large complexes. (icr.ac.uk)
Microscopy2
  • Confocal microscopy revealed a partial colocalization of Tax with nuclear proteasomes. (ox.ac.uk)
  • Immunofluorescence and electron microscopy with immunogold labeling revealed that the 20S, 19S, and 11S subunits of the 26S proteasome, the molecular chaperones BiP/GRP78, Hsp70, and Hsp40, as well as the RNA-binding protein TIA-1, the potential chaperone 14-3-3, and alpha-synuclein colocalize with the perinuclear inclusions. (mdc-berlin.de)
Subunits1
  • This effect was not due to the induction of the LMP2 and LMP7 proteasome subunits. (ox.ac.uk)
Inhibition2
  • Most importantly, inhibition of the proteasome was of functional relevance for UVA-induced MMP-1 expression, because overexpression of the proteasome or the protein repair enzyme methionine sulfoxide reductase prevented the UVA-induced induction of MMP-1. (nih.gov)
  • Inhibition of proteasome activity resulted in a twofold increase in the amount of ubiquitinated, SDS-resistant aggregates, indicating that inclusion bodies accumulate when the capacity of the ubiquitin-proteasome system to degrade aggregation-prone huntingtin protein is exhausted. (mdc-berlin.de)
Pathways1
  • Methods: In 22 muscles from dysferlinopathy patients we investigated fiber atrophy by morphometry and ubiquitin-proteasome and autophagic pathways using protein and/or transcriptional analysis of atrophy- and autophagy-related genes (MuRF1, atrogin1, LC3, p62, Bnip3). (elsevier.com)
Chromatin1
  • Genome-wide chromatin immunoprecipitation analyses revealed that proteasome substituents are associated with the majority of yeast genes. (elsevier.com)
Thermoplasma1
  • Single cystals of proteasomes from the archaebacterium Thermoplasma acidophilum were obtained using the hanging-drop vapor diffusion method. (mpg.de)
Tumor1
  • Along with inhibiting the proteasome and thus sensitizing tumor cells to apoptosis, bortezomib may also have multiple effects on the host immune responses. (elsevier.com)
Yeast1
  • Although the data support the presence of the intact 26 S proteasome on most genes, several hundred yeast genes were cross-linked to either the 20 or 19 S complex but not both, consistent with some degree of independent function for the proteasomal subcomplexes. (elsevier.com)
Intracellular1
  • In the present study we identify the proteasome as an integral part of the UVA-induced, intracellular signaling cascade in human dermal fibroblasts. (nih.gov)
Multisubunit2
  • The 20S proteasome, multisubunit proteolytic complex, is the central. (systemsbiology.net)
  • A multisubunit barrel shaped endoprotease complex, which is the core of the proteasome complex. (systemsbiology.net)
Mice1
  • Here we report the preparation and characterization of mice that express the recombinase Cre instead of β5t, a proteasome subunit that is abundant in cTECs and not detected in other cell types, including mTECs. (ox.ac.uk)
Cells2
  • While proteasomes are found in many types of cells, immunoproteasomes are located primarily in immune system cells. (medlineplus.gov)
  • 2007) report that a protein ubiquitylation complex and the proteasome are required for the clearance of apoptotic cells in Drosophila. (cnrs.fr)
Molecules1
  • The unit cell dimensions and crystal symmetry together with the shape and size of the proteasome suggest a packing arrangement of proteasome molecules in the unit cell, with their cylinder axis nearly parallel to the crystallographic a-axis. (mpg.de)
Induction2
  • Results: Dysferlinopathy showed significant fiber atrophy and higher MuRF-1 protein and mRNA levels, which correlated with fiber size, suggesting activation of the atrophy program by proteasome induction. (elsevier.com)
  • Conclusions: Some of the MuRF-1 upregulation and proteasome induction may be attributed to the prominent regeneration found. (elsevier.com)
Mechanism1
  • Dendritic cell maturation enhances CD8+ T-cell responses to exogenous antigen via a proteasome-independent mechanism of major histocompatibility complex class I loading. (ed.ac.uk)
Transcriptional2
  • The cellular response to nutrient limitation at the molecular level is the outcome of complex, orchestrated interactions among transcriptional, translational, posttranslational, and metabolic profiles. (biomedcentral.com)
  • Conclusion: In summary, we show that the transcriptional response to acute cell stress is largely transient and proteosome-centric. (elsevier.com)