The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli.
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.
Databases containing information about PROTEINS such as AMINO ACID SEQUENCE; PROTEIN CONFORMATION; and other properties.
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.
A serotype of Salmonella enterica that is a frequent agent of Salmonella gastroenteritis in humans. It also causes PARATYPHOID FEVER.
A process that includes the determination of AMINO ACID SEQUENCE of a protein (or peptide, oligopeptide or peptide fragment) and the information analysis of the sequence.
Compounds that inhibit the function or proteolytic action of the PROTEASOME.
One of the ESTROGEN RECEPTORS that has marked affinity for ESTRADIOL. Its expression and function differs from, and in some ways opposes, ESTROGEN RECEPTOR BETA.
Compounds that interact with ESTROGEN RECEPTORS in target tissues to bring about the effects similar to those of ESTRADIOL. Estrogens stimulate the female reproductive organs, and the development of secondary female SEX CHARACTERISTICS. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds.
A highly conserved 76-amino acid peptide universally found in eukaryotic cells that functions as a marker for intracellular PROTEIN TRANSPORT and degradation. Ubiquitin becomes activated through a series of complicated steps and forms an isopeptide bond to lysine residues of specific proteins within the cell. These "ubiquitinated" proteins can be recognized and degraded by proteosomes or be transported to specific compartments within the cell.
One of the ESTROGEN RECEPTORS that has greater affinity for ISOFLAVONES than ESTROGEN RECEPTOR ALPHA does. There is great sequence homology with ER alpha in the DNA-binding domain but not in the ligand binding and hinge domains.
Cytoplasmic proteins that bind estrogens and migrate to the nucleus where they regulate DNA transcription. Evaluation of the state of estrogen receptors in breast cancer patients has become clinically important.
A plant family of the order Proteales, subclass Rosidae class Magnoliopsida. Cluster roots, bottlebrush-like clusters of rootlets which form in response to poor soil, are common in this family.
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.
A mitosporic Loculoascomycetes fungal genus including some economically important plant parasites. Teleomorphs include Mycosphaerella and Venturia.
Immature ERYTHROCYTES. In humans, these are ERYTHROID CELLS that have just undergone extrusion of their CELL NUCLEUS. They still contain some organelles that gradually decrease in number as the cells mature. RIBOSOMES are last to disappear. Certain staining techniques cause components of the ribosomes to precipitate into characteristic "reticulum" (not the same as the ENDOPLASMIC RETICULUM), hence the name reticulocytes.
Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
An analysis comparing the allele frequencies of all available (or a whole GENOME representative set of) polymorphic markers in unrelated patients with a specific symptom or disease condition, and those of healthy controls to identify markers associated with a specific disease or condition.
A quantitative method of combining the results of independent studies (usually drawn from the published literature) and synthesizing summaries and conclusions which may be used to evaluate therapeutic effectiveness, plan new studies, etc., with application chiefly in the areas of research and medicine.
Studies which start with the identification of persons with a disease of interest and a control (comparison, referent) group without the disease. The relationship of an attribute to the disease is examined by comparing diseased and non-diseased persons with regard to the frequency or levels of the attribute in each group.
A latent susceptibility to disease at the genetic level, which may be activated under certain conditions.
Genetic loci associated with a QUANTITATIVE TRAIT.
A single nucleotide variation in a genetic sequence that occurs at appreciable frequency in the population.
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.
Proteins obtained from ESCHERICHIA COLI.
Proteins prepared by recombinant DNA technology.
A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.
Genes that cause the epigenotype (i.e., the interrelated developmental pathways through which the adult organism is realized) to switch to an alternate cell lineage-related pathway. Switch complexes control the expression of normal functional development as well as oncogenic transformation.
The field of biology which deals with the process of the growth and differentiation of an organism.
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.
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.
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.
Exogenous and endogenous compounds which inhibit CYSTEINE ENDOPEPTIDASES.
Software used to locate data or information stored in machine-readable form locally or at a distance such as an INTERNET site.
A metallocarboxypeptidase that is predominantly expressed as a membrane-bound enzyme. It catalyzes the hydrolysis of an unsubstituted, C-terminal glutamyl residue, typically from PTEROYLPOLYGLUTAMIC ACIDS. It was formerly classified as EC 3.4.19.8.
Databases devoted to knowledge about specific genes and gene products.
The complete genetic complement contained in the DNA of a set of CHROMOSOMES in a HUMAN. The length of the human genome is about 3 billion base pairs.
Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).

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)

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. ...
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 ...
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 ...
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 ...
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 ...
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
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 ...
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
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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 ...
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 ...
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 ...
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. ...
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 ...
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 ...
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 ...
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 ...
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 ...
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.
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 ...
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 ...
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.
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 ...
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 …
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 ...
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 ...
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 ...
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. ...
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
PDCD5 mediates ubiquitin-dependent proteasomal degradation of HDAC3 via C-terminal cleavage of HDAC3.(a) MG132 treatment induces accumulation of cleaved HDAC3.
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 ...
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 ...
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 ...
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 ...
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 ...
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.
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 ...
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 ...
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.
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.
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 ...
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]. ...
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 ...
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 ...
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 ...
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 ...
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 ...
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 ...
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 ...
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 …
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, ...
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. ...
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
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 ...
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 ...
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 ...
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 ...
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 ...
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 ...
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.
Fingerprint Dive into the research topics of Proteasome subunits differentially control myeloma cell viability and proteasome inhibitor sensitivity. Together they form a unique fingerprint. ...
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 ...
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
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 ...
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 ...
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 ...
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.
At Novus Biologicals, we recently added a new RNA Polymerase II antibody (clone 4H8) to our antibody catalog. RNAPII is an essential transcription enzyme,
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 ...
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: ... Now included with EC 3.4.22.53 (calpain-2) and EC 3.4.25.1 (proteasome endopeptidase complex) EC 3.4.24.6: leucolysin EC 3.4. ... proteasome endopeptidase complex EC 3.4.22.22: Transferred entry: yeast cysteine proteinase D. Now EC 3.4.24.37, saccharolysin ...
... a form of pectin Proteasome endopeptidase complex, an enzyme Manual call point, a common device for manual fire alarm ...
... 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- ...
... 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. ...
"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 ...
... (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) Biology portal. ... 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 ...
... 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 protease family ATP-dependent Clp protease proteolytic subunit Gottesman S, Clark WP, Maurizi MR (May 1990 ... ClpAP, ClpXP and ClpYQ coexist in E. Coli while only ClpXP complex in present in humans as mitochondrial enzymes. ClpYQ is ...
"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 ... "The 1.9 A structure of a proteasome-11S activator complex and implications for proteasome-PAN/PA700 interactions". Molecular ... Proteasomes are protein complexes which degrade unneeded or damaged proteins by proteolysis, a chemical reaction that breaks ...
Threonine endopeptidase *Proteasome endopeptidase complex. *HslU-HslV peptidase. *Other/ungrouped: Amyloid precursor protein ... Aspartic endopeptidases EC 3.4.23. of vertebrate, fungal and retroviral origin have been characterised.[1] More recently, ... Many eukaryotic aspartic endopeptidases (MEROPS peptidase family A1) are synthesised with signal and propeptides. The animal ... Aspartic+Endopeptidases at the US National Library of Medicine Medical Subject Headings (MeSH) ...
Threonine endopeptidase *Proteasome endopeptidase complex. *HslU-HslV peptidase. *Other/ungrouped: Amyloid precursor protein ... serine-type endopeptidase activity. Cellular component. • lamellipodium membrane. • extracellular exosome. • lysosomal membrane ... Dipeptidyl peptidase-4 (DPP4), also known as adenosine deaminase complexing protein 2 or CD26 (cluster of differentiation 26) ... 1r9n: Crystal Structure of human dipeptidyl peptidase IV in complex with a decapeptide (tNPY) at 2.3 Ang. Resolution ...
Threonine endopeptidase *Proteasome endopeptidase complex. *HslU-HslV peptidase. *Other/ungrouped: Amyloid precursor protein ... By complex cooperative action the proteases may proceed as cascade reactions, which result in rapid and efficient amplification ... The structure of a protease (TEV protease) complexed with its peptide substrate in black with catalytic residues in red.(PDB: ... Bacteria contain proteases responsible for general protein quality control (e.g. the AAA+ proteasome) by degrading unfolded or ...
Threonine endopeptidase *Proteasome endopeptidase complex. *HslU-HslV peptidase. *Other/ungrouped: Amyloid precursor protein ... The formation of this complex provides a protective role for stability and activity. It is protective for β-galactosidase and ... This gene encodes a glycoprotein that associates with lysosomal enzymes beta-galactosidase and neuraminidase to form a complex ...
Threonine endopeptidase *Proteasome endopeptidase complex. *HslU-HslV peptidase. *Other/ungrouped: Amyloid precursor protein ... endopeptidase activity. • amyloid-beta binding. • beta-aspartyl-peptidase activity. • GO:0001948 protein binding. • enzyme ... aspartic-type endopeptidase activity. Cellular component. • multivesicular body. • late endosome. • endoplasmic reticulum lumen ... 2ohm: X-ray crystal structure of beta secretase complexed with N~3~-benzylpyridine-2,3-diamine ...
Threonine endopeptidase *Proteasome endopeptidase complex. *HslU-HslV peptidase. *Other/ungrouped: Amyloid precursor protein ...
"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 ...
... 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 ...
... 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 ...
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 ...
By complex cooperative action the proteases may proceed as cascade reactions, which result in rapid and efficient amplification ... Bacteria contain proteases responsible for general protein quality control (e.g. the AAA+ proteasome) by degrading unfolded or ... endopeptidases, such as trypsin, chymotrypsin, pepsin, papain, elastase). Catalysis is achieved by one of two mechanisms: ...
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 ...
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 Mpro, formally known as C30 Endopeptidase, is the main protease found in coronaviruses. It ... 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. ...
The structure of the insulin-insulin receptor complex has been determined using the techniques of X-ray crystallography. The ... MafA is degraded by proteasomes upon low blood glucose levels. Increased levels of glucose make an unknown protein glycosylated ... The endopeptidases cleave at 2 positions, releasing a fragment called the C-peptide, and leaving 2 peptide chains, the B- and A ... Polycystic ovary syndrome - a complex syndrome in women in the reproductive years where anovulation and androgen excess are ...
proteasome complex. • cnewyllyn cell. • cytosolic proteasome complex. • nucleoplasm. • Mitocondria. • Cytosol. • Ino80 complex ... endopeptidase inhibitor activity. • hydrolase activity. • RNA binding. • proteasome binding. Cydrannau o'r gell. • cytoplasm. • ... "Crystal structure of the catalytic domain of UCHL5, a proteasome-associated human deubiquitinating enzyme, reveals an ... negative regulation of endopeptidase activity. • protein deubiquitination. • negative regulation of proteasomal ubiquitin- ...
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. doi: ...
chromatin silencing complex. • mitochondrion. • cell nucleus. • ESC/E(Z) complex. • nucleolus. • nuclear chromatin. • chromatin ... proteasome-mediated ubiquitin-dependent protein catabolic process. • apoptotic process. • peptidyl-lysine deacetylation. • ... positive regulation of cysteine-type endopeptidase activity involved in apoptotic process. • regulation of glucose metabolic ... SIRT1, along with HDAC1 and the AP-1 promoter complex within D1-type dopaminergic medium spiny neurons, appears to be closely ...
By complex cooperative action the proteases may proceed as cascade reactions, which result in rapid and efficient amplification ... Bacteria contain proteases responsible for general protein quality control (e.g. the AAA+ proteasome) by degrading unfolded or ... endopeptidases, such as trypsin, chymotrypsin, pepsin, papain, elastase). ... The structure of a protease (TEV protease) complexed with its peptide substrate in black with catalytic residues in red.(PDB: ...
ribonucleoprotein complex binding. • protein N-terminus binding. • ubiquitin protein ligase activity. • NEDD8 ligase activity. ... Mdm2 auto ubiquitylates itself, which allows for its degradation by the proteasome. Mdm2 also interacts with a ubiquitin ... negative regulation of cysteine-type endopeptidase activity involved in apoptotic process. • positive regulation of proteasomal ... macromolecular complex. Biological process. • negative regulation of signal transduction by p53 class mediator. • endocardial ...
Proteasome 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) ... multicatalytic proteinase (complex), MCP, proteasome, large multicatalytic protease, proteasome organelle, alkaline protease, ... Retrieved from "https://en.wikipedia.org/w/index.php?title=Proteasome_endopeptidase_complex&oldid=826116286" ...
... and complex assemblies. As a member of the wwPDB, the RCSB PDB curates and annotates PDB data according to agreed upon ...
It contains a 700-kDa catalytic sub-complex and two 700-kDa regulatory sub-complexes. The complex digests ubiquitinated ... A large multisubunit complex that plays an important role in the degradation of most of the cytosolic and nuclear proteins in ... Complex, Proteasome Endopeptidase; Endopeptidase Complex, Multicatalytic; Endopeptidase Complex, Proteasome; Proteasome, 20S; ... Proteasome Endopeptidase Complex (Proteasome). Subscribe to New Research on Proteasome Endopeptidase Complex ...
Proteasome Endopeptidase Complex (Proteasome) Summary Description: A large multisubunit complex that plays an important role in ... Also Known As: Proteasome; Multicatalytic Endopeptidase Complex; 20S Proteasome; Ingensin; Macropain Show All ,, Networked: ... Key Diseases for which Proteasome Endopeptidase Complex is Relevant. * Multiple Myeloma : 84 outcomes 74 studies in 693 results ... It contains a 700-kDa catalytic sub-complex and two 700-kDa regulatory sub-complexes. The complex digests ubiquitinated ...
"Proteasome Endopeptidase Complex" by people in this website by year, and whether "Proteasome Endopeptidase Complex" was a major ... Proteasome Endopeptidase Complex*Proteasome Endopeptidase Complex. *Complex, Proteasome Endopeptidase. *Endopeptidase Complex, ... "Proteasome Endopeptidase Complex" is a descriptor in the National Library of Medicines controlled vocabulary thesaurus, MeSH ( ... Below are the most recent publications written about "Proteasome Endopeptidase Complex" by people in Profiles. ...
Proteasome Endopeptidase Complex. Grant support. *P30 EB009998/EB/NIBIB NIH HHS/United States ... possesses a proteasome system analogous to the eukaryotic ubiquitin-proteasome pathway. Mtb requires the proteasome to resist ... The Mtb proteasome has a tightly closed gate in the crystal structure of the T1A mutant 20S proteasome. (A) A space-filling ... C) Proposed structural changes accompanying the assembly of the Mtb 20S proteasome, starting from the half proteasome to the ...
GO:0004175 endopeptidase activity Cellular Component. GO:0005839 proteasome core complex Contributing signatures. Signatures ... Proteasomes. Multicatalytic proteinase complexes.. Enzyme Protein 47 187-8 1993. Hilt W, Wolf DH. Proteasomes: destruction as a ... Proteasome, subunit alpha/beta (IPR001353) *Proteasome B-type subunit (IPR023333) *Peptidase T1A, proteasome beta-subunit ( ... Peptidase T1A, proteasome beta-subunit (IPR000243). Short name: Pept_T1A_subB Family relationships * ...
multicatalytic endopeptidase complex beta chain. proteasome (prosome, macropain) subunit, beta type, 4. proteasome beta chain. ... proteasome_beta_type_4; proteasome beta type-4 subunit. The 20S proteasome, multisubunit proteolytic complex, is the central ... proteasome core complex, beta-subunit complex ISS Inferred from Sequence or Structural Similarity. more info ... proteasome chain 3. proteasome subunit HsN3. proteasome subunit, beta type, 4. testis tissue sperm-binding protein Li 79P. NP_ ...
The p105 precursor of the p50 subunit of NF-kappa B is processed in vitro by an ATP-dependent process that requires proteasomes ... We demonstrate an essential role for the proteasome complex in two proteolytic processes required for activation of the ... Proteasome Endopeptidase Complex * benzyloxycarbonylleucyl-leucyl-leucine aldehyde Grant support * AI20642/AI/NIAID NIH HHS/ ... We demonstrate an essential role for the proteasome complex in two proteolytic processes required for activation of the ...
Proteasome Endopeptidase Complex / genetics * Proteasome Endopeptidase Complex / metabolism * Reverse Transcriptase Polymerase ...
Proteasome Endopeptidase Complex. *Proteasome Endopeptidase Complex: chemistry. *Protein Conformation. *Rats. *Recombinant ...
Multicatalytic endopeptidase complex subunit C9) (Proteasome component C9) (Proteasome subunit L) ... IPR023332 Proteasome_alpha-type. IPR000426 Proteasome_asu_N. IPR001353 Proteasome_sua/b. ... IPR023332 Proteasome_alpha-type. IPR000426 Proteasome_asu_N. IPR001353 Proteasome_sua/b. ... Proteasome subunit alpha type-4. Proteasome subunit alpha type-4, EC 3.4.25.1 (Macropain subunit C9) ( ...
alpha subunit; endopeptidase; prc1 gene; proteosome; prc1; multicatalytic endopeptidase complex, proteasome component, alpha ... beta subunit; endopeptidase; prcgb gene; proteosome; prcgb; multicatalytic endopeptidase complex, proteasome component, beta ... alpha subunit; endopeptidase; prc8 gene; proteosome; prc8; multicatalytic endopeptidase complex, proteasome component, alpha ... beta subunit; endopeptidase; prch gene; proteosome; prch; multicatalytic endopeptidase complex, proteasome component, beta ...
20S-PA28 complex). Within the 20S core complex, PSMB5 displays a chymotrypsin-like activity. ... The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that ... This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with ... This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a ...
... proteolytic complex that, in reticulocyte extracts, can be formed by the association of three factors: CF-1, CF-2, and CF-3. ... Multienzyme Complexes / chemistry, metabolism*. Protease Inhibitors / chemistry*. Proteasome Endopeptidase Complex. Proteins / ... Cysteine Endopeptidases; EC 3.4.25.1/Proteasome Endopeptidase Complex ... When CF-1, ATP, and Mg2+ were also present, the 125I-labeled inhibitor along with the proteasome formed a complex of 1500 kDa. ...
Multienzyme Complexes / antagonists & inhibitors*. Proteasome Endopeptidase Complex. Proto-Oncogene Proteins / drug effects, ... Cysteine Endopeptidases; EC 3.4.25.1/Proteasome Endopeptidase Complex ... Cysteine Endopeptidases. Cysteine Proteinase Inhibitors / pharmacology*. Dose-Response Relationship, Drug. Humans. Leukemia, ... CONCLUSION: Proteasome inhibition is highly effective in proliferating B-CLL cells and induces apoptosis using a caspase- ...
Proteasome Endopeptidase Complex. *Single Nucleotide Polymorphism. *Adolescents. *Alleles. *Messenger RNA. *DNA Sequence ... acetylcholine-gated channel complex - behavioral response to nicotine - cell junction - dendrite - integral to membrane - ion ... We demonstrate the intermediate phenotype can potentially enhance the power of complex disease association analysis and the ... Genetic association analysis of complex diseases incorporating intermediate phenotype information.. PLoS One. 2012; 7(10): ...
Buy our Recombinant Human Proteasome 20S alpha 2 protein. Ab116173 is a full length protein produced in Escherichia coli and ... Multicatalytic endopeptidase complex subunit C3. *PMSA2. *Proteasome (prosome macropain) subunit alpha type 2 ... The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, ... PSMA2 may have a potential regulatory effect on another component(s) of the proteasome complex through tyrosine phosphorylation ...
Buy our Recombinant Human Proteasome 20S alpha 5 protein. Ab123211 is a full length protein produced in Escherichia coli and ... Multicatalytic endopeptidase complex zeta chain. *Proteasome (prosome macropain) subunit alpha type 5 ... The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, ... Recombinant Human Proteasome 20S alpha 5 protein. See all Proteasome 20S alpha 5 proteins and peptides. ...
"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 ...
Proteasome Endopeptidase Complex; Proteasome Inhibitors ...
Proteasome Endopeptidase Complex; Proteasome Inhibitors ... Cromm PM, Crews CM: The Proteasome in Modern Drug Discovery: ... 2008) Proteasome Inhibitors in Cancer Chemotherapy, Cancer: Principles and Practice of Oncology, 8th Ed. V.T DeVita, T.S. ... Hines J, Groll M, Fahnestock M, Crews CM: Proteasome inhibition by fellutamide B induces nerve growth factor synthesis. Chem ... Schneekloth JS Jr, Crews CM: Natural product inhibitors of the ubiquitin-proteasome pathway. Curr Drug Targets. 2011 Oct. PMID ...
Proteasome Endopeptidase Complex. Cyclin B1. Tosylarginine Methyl Ester. Ubiquitination. Time-Lapse Imaging. Carbamates. ... Ubiquitin-Protein Ligase Complexes. Polyploidy. Aneuploidy. Cytokinesis. Cyclin B. Chromosomes, Human. RNA Interference. ...
Proteasome Endopeptidase Complex). ... catenin destruction complex.. [Mh] Termos MeSH prim rio:. Prote ... Complexo de Endopeptidases do Proteassoma/fisiologia. Prote lise. Sulfonas/farmacologia. Tanquirases/antagonistas & inibidores ... AXIN1 and AXIN2/Conductin, the rate-limiting factors for the stability and function of endogenous destruction complexes, are ... catenin destruction complexes. In SW480 colorectal cancer cells treated with the tankyrase inhibitor (TNKSi) G007-LK we found ...
Proteasome Endopeptidase Complex); K848JZ4886 (Cysteine). ... Complexo de Endopeptidases do Proteassoma/gen tica. Complexo de ... Serina Endopeptidases/gen tica. Serina Endopeptidases/metabolismo. Caracteres Sexuais. Resposta a Prote nas n o Dobradas/gen ... Complexo de Endopeptidases do Proteassoma/metabolismo. Subunidades Proteicas/metabolismo. RNA Mensageiro/gen tica. RNA ... Furthermore, we showed that, in the absence of ERα, G93A-SOD1 failed to activate OMI and the proteasome, confirming the ERα ...
... proteasome activity. Specifically, we demonstrate that knockout of FoxO1, but not of FoxO3, in mice severely impairs proteasome ... proteasome activity. Specifically, we demonstrate that knockout of FoxO1, but not of FoxO3, in mice severely impairs proteasome ... The proteasome is the main cellular proteolytic system and plays a fundamental role in the maintenance of protein homeostasis. ... Importantly, we show that FoxO1 directly binds on the promoter region of the rate-limiting catalytic β5 proteasome subunit to ...
Proteasome Subunit Alpha 3, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The ... Proteasome (Prosome, Macropain) Subunit, Alpha Type, 3 2 3 * Multicatalytic Endopeptidase Complex Subunit C8 3 4 ... The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is a barrel- ... The proteasome is a multicatalytic proteinase complex with a highly ordered ring-shaped 20S core structure. The core structure ...
Proteasome Subunit Beta 8, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human ... Proteasome Subunit Beta 8 2 3 5 * Multicatalytic Endopeptidase Complex Subunit C13 3 4 ... The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is composed of 28 ... The proteasome is a multicatalytic proteinase complex with a highly ordered ring-shaped 20S core structure. The core structure ...
Expression profiling is a powerful method for identifying networks of pleiotropic genes regulating complex traits, but the ... A major challenge of modern biology is to understand the networks of interacting genes regulating complex traits, and the ... Proteasome alpha6 subunit 43E18. Proteasome endopeptidase. Proteolysis and peptidolysis. 20S core proteasome complex ... This comparison has not been possible to date because there are only a few complex traits for which the genetic architecture is ...
  • A large multisubunit complex that plays an important role in the degradation of most of the cytosolic and nuclear proteins in eukaryotic cells. (curehunter.com)
  • The complex digests ubiquitinated proteins and protein activated via ornithine decarboxylase antizyme. (curehunter.com)
  • Most proteasome subunits can be classified, on the basis on sequence similarities into two groups, alpha (A) and beta (B). These are arranged in four rings of seven proteins, consisting of a ring of alpha subunits, two rings of beta subunits, and a ring of alpha subunits. (ebi.ac.uk)
  • Thus, the ubiquitin-proteasome pathway functions not only in the complete degradation of polypeptides, but also in the regulated processing of precursors into active proteins. (nih.gov)
  • Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. (uniprot.org)
  • Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. (uniprot.org)
  • The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. (uniprot.org)
  • Proteins conjugated to ubiquitin are degraded by a 26S (1500-kDa) proteolytic complex that, in reticulocyte extracts, can be formed by the association of three factors: CF-1, CF-2, and CF-3. (biomedsearch.com)
  • 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)
  • Prompt removal of misfolded membrane proteins and misassembled membrane protein complexes is essential for membrane homeostasis. (bireme.br)
  • Specifically, we have demonstrated that the accumulation of damaged proteins during aging is connected to an age-related downregulation of proteasome expression and activity. (frontiersin.org)
  • Proteasomes are protein complexes which degrade unneeded or damaged proteins by proteolysis, a chemical reaction that breaks peptide bonds. (wikipedia.org)
  • Proteasomes are part of a major mechanism by which cells regulate the concentration of particular proteins and degrade misfolded proteins. (wikipedia.org)
  • Before the discovery of the ubiquitin-proteasome system, protein degradation in cells was thought to rely mainly on lysosomes, membrane-bound organelles with acidic and protease-filled interiors that can degrade and then recycle exogenous proteins and aged or damaged organelles. (wikipedia.org)
  • The 26S proteasome has specificity for ubiquitinylated protein substrates and hydrolyses ATP during proteolysis of ubiquitinylated proteins. (usp.br)
  • 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. (harvard.edu)
  • The 20S proteolytic core of the proteasome is hollow and provides an enclosed cavity open at both ends in which proteins are degraded ( 7 ). (mcponline.org)
  • Complexes composed of multiple proteins regulate most cellular functions. (umassmed.edu)
  • The proteasome is a large barrel-shaped particle present in the cytosol and nucleus of all eukaryotic cells ( 3 - 5 ) that is responsible for degrading of a majority of cellular proteins ( 6 ) ( Fig. 1 ). (jimmunol.org)
  • Plastids contain tetradecameric Clp protease core complexes, with five ClpP Ser-type proteases, four nonproteolytic ClpR, and two associated ClpS proteins. (plantcell.org)
  • Interestingly, a subpopulation of PsaF and several light-harvesting complex II proteins accumulated in the thylakoid with unprocessed chloroplast transit peptides. (plantcell.org)
  • In particular, the expression of 14-3-3e, α-enolase, α-tubulin and splice isoform 2 of α3 proteasome subunit changed as a consequence of the down-modulation of Vav1 during the differentiation of both HL-60 and NB4 cell lines, suggesting that these proteins may constitute a common part of the ATRA-induced pathway during maturation of APL-derived promyelocytes. (elsevier.com)
  • The proteasome (or macropain) ( EC:3.4.25.1 ) [ PMID: 7682410 , PMID: 2643381 , PMID: 1317508 , PMID: 7697118 , PMID: 8882582 ] is a multicatalytic proteinase complex in eukaryotes and archaea, and in some bacteria, that seems to be involved in an ATP/ubiquitin-dependent nonlysosomal proteolytic pathway. (ebi.ac.uk)
  • Antigen standard for proteasome (prosome, macropain) subunit, beta type, 7 (PSMB7) is a lysate prepared from HEK293T cells transiently transfected with a TrueORF gene-carrying pCMV plasmid and then lysed in RIPA Buffer. (creativebiomart.net)
  • GO annotations related to this gene include endopeptidase activity and threonine-type endopeptidase activity . (genecards.org)
  • Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. (uniprot.org)
  • When the inhibitor, proteasome, and CF-1 were incubated together in the presence of ATP and Mg2+, degradation of ubiquitin-125I-lysozyme occurred. (biomedsearch.com)
  • More recently, we have explored the use of small molecules to control intracellular protein levels, either by inhibiting their degradation or by inducing their proteolysis via the 26S proteasome. (yalecancercenter.org)
  • FUNCTION: Protease subunit of a proteasome-like degradation CC complex believed to be a general protein degrading machinery. (univ-lyon1.fr)
  • The overall system of ubiquitination and proteasomal degradation is known as the ubiquitin-proteasome system. (wikipedia.org)
  • Later, the ATP-dependent proteolytic complex that was responsible for ubiquitin-dependent protein degradation was discovered and was called the 26S proteasome. (wikipedia.org)
  • Under these conditions, the rapid decay of the protein occurring after induction is accounted for by efficient recognition and degradation by the proteasome. (cnrs.fr)
  • Boyer SN, Wazer DE, Band V. (1996) E7 protein of human papilloma virus-16 induces degradation of retinoblastoma protein through the ubiquitin-proteasome pathway. (springer.com)
  • Proteasomes are the main proteases responsible for protein degradation and the production of major histocompatibility complex I (MHC I) 1 ligands ( 1 - 4 ). (mcponline.org)
  • Here, we identify a cascade of specific protein interactions that protect LIM-HD multiprotein complexes from proteasomal degradation. (umassmed.edu)
  • Together, our results indicate a combinatorial code that selects specific multiprotein complexes via proteasomal degradation in cells with broad implications for the assembly and specificity of multiprotein complexes. (umassmed.edu)
  • These data suggest that shear stress promotes the disassembly and degradation of the keratin IF network via phosphorylation and the ubiquitin-proteasome pathway. (northwestern.edu)
  • We biochemically demonstrate that the TSC2 A415V mutation is functionally deleterious, leading to shortened half-life and proteasome-mediated protein degradation. (elsevier.com)
  • We demonstrate an essential role for the proteasome complex in two proteolytic processes required for activation of the transcription factor NF-kappa B. The p105 precursor of the p50 subunit of NF-kappa B is processed in vitro by an ATP-dependent process that requires proteasomes and ubiquitin conjugation. (nih.gov)
  • The proteasome has an ATP-dependent proteolytic activity. (abcam.com)
  • The proteasome is the main cellular proteolytic system and plays a fundamental role in the maintenance of protein homeostasis. (frontiersin.org)
  • The proteolytic activities of this system were isolated as a multi-protein complex originally called the multi-catalytic proteinase complex by Sherwin Wilk and Marion Orlowski. (wikipedia.org)
  • This multicatalytic proteinase complex is composed of a catalytic core, 20S proteasome, which have multiple proteolytic activities (trypsin-like, chymotrypsin-like, peptidylglutamtyl-peptide hydrolyzing, BrAAP and SNAAP). (usp.br)
  • The proteolytic properties of the proteasome are adapted to the requirements of the immune system by proteasome components whose synthesis is under the control of interferon-γ. (springer.com)
  • IFN-γ stimulation modulates the proteolytic activity and cleavage site preference of 20S mouse proteasomes. (springer.com)
  • Ubiquitin-proteasome proteolytic pathway is involved in a number of cellular physiology. (elsevier.com)
  • Although a pivotal role of proteasomes in the proteolytic generation of epitopes for major histocompatibility complex (MHC) class I presentation is undisputed, their precise function is currently the subject of an active debate: do proteasomes generate many epitopes in definitive form, or do they merely generate the COOH termini, whereas the definitive NH 2 termini are cleaved by aminopeptidases? (elsevier.com)
  • Proteolysis, proteasomes and antigen presentation. (ebi.ac.uk)
  • This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex). (uniprot.org)
  • The inhibitor (CF-2) thus appears to be an ATP-binding component that regulates proteolysis within the 1500-kDa complex. (biomedsearch.com)
  • Our previous work has established a direct association between proteasome-mediated proteolysis and aging. (frontiersin.org)
  • Proteasome-mediated proteolysis plays a crucial role in many basic cellular processes. (mcponline.org)
  • Although the eukaryotic proteasome core particles close their protein substrate entrance gates with different amino terminal peptides of the seven alpha-subunits, it has been unknown how a prokaryotic proteasome might close the gate at the symmetry axis with seven identical peptides. (nih.gov)
  • E - H ) The translation and rotation of the individual α- and β-subunits in the Mtb half proteasome required for reaching the full Mtb 20S proteasome structure. (nih.gov)
  • In eukaryotes the proteasome is composed of 28 distinct subunits which form a highly ordered ring-shaped structure (20S ring) of about 700 kDa. (ebi.ac.uk)
  • However, the mechanisms underlying this age-related decline of proteasome function and the down-regulation in expression of its subunits remain largely unclear. (frontiersin.org)
  • The 20S core proteasome has barrel-like configuration and is comprised by seven different α subunits and seven distinct β subunits. (frontiersin.org)
  • The proteasome subcomponents are often referred to by their Svedberg sedimentation coefficient (denoted S). The proteasome most exclusively used in mammals is the cytosolic 26S proteasome, which is about 2000 kilodaltons (kDa) in molecular mass containing one 20S protein subunit and two 19S regulatory cap subunits. (wikipedia.org)
  • Proteasomal ATPase OB C-terminal domain / Proteasome beta-type subunits signature. (pdbj.org)
  • Proteasome subunit A N-terminal signature / Proteasome beta subunits C terminal / Maintenance of mitochondrial structure and function / Ubiquitin domain signature. (pdbj.org)
  • Proteasome alpha-type subunits signature. (pdbj.org)
  • Proteasome subunit alpha 3 / DSS1/SEM1 / N-glycan trimming in the ER and Calnexin/Calreticulin cycle / Proteasome beta-type subunits signature. (pdbj.org)
  • Autodegradation of Cdh1 by Cdh1:APC/C / UCH proteinases / Proteasome alpha-type subunits signature. (pdbj.org)
  • SUBUNIT: The 26S proteasome consists of a 20S proteasome core and CC two 19S regulatory subunits. (univ-lyon1.fr)
  • Among these are three subunits with catalytic sites that are incorporated into the enzyme complex during its de novo synthesis. (springer.com)
  • Arnold D, Driscoll J, Androlewicz M, Hughes E, Cresswell P, Spiess T (1992) Proteasome subunits encoded in the MHC are not generally required for the processing of peptides bound by MHC class I molecules. (springer.com)
  • The eukaryotic 20S particle is composed of 14 different subunits organized in a barrel-shaped complex with the stoichiometry α 7 β 7 β 7 α 7 . (mcponline.org)
  • In IPs, the three catalytic β-subunits expressed in CPs are replaced by three interferon-γ-inducible homologues (immunosubunits): low molecular weight protein (LMP)-2 (or β1i) for β1, multicatalytic endopeptidase complex-like (MECL)-1 (or β2i) for β2, and LMP7 (or β5i) for β5. (mcponline.org)
  • Differential stable isotope labeling of the ClpPRS complex with iTRAQ revealed a fivefold reduction in assembled ClpR2 accumulation and twofold to fivefold reductions in the other subunits. (plantcell.org)
  • p105 processing can be blocked in intact cells with inhibitors of the proteasome or in yeast with proteasome mutants. (nih.gov)
  • Inhibited by mercurial reagents and some inhibitors of serine endopeptidases. (cathdb.info)
  • A humanized yeast proteasome identifies unique binding modes of inhibitors for the immunosubunit beta 5i. (cathdb.info)
  • Systematic Analyses of Substrate Preferences of 20S Proteasomes Using Peptidic Epoxyketone Inhibitors. (cathdb.info)
  • 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 proteasome's threonine-active sites. (jimmunol.org)
  • Active site-directed inhibitors of Rhodococcus 20 S proteasome. (elsevier.com)
  • 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. (frontiersin.org)
  • Expression of this gene is induced by gamma interferon and this gene product replaces catalytic subunit 3 (proteasome beta 5 subunit) in the immunoproteasome. (genecards.org)
  • We found in the new Mtb proteasome crystal structure that the gate is tightly sealed by the seven identical peptides taking on three distinct conformations. (nih.gov)
  • Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. (nih.gov)
  • An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. (nih.gov)
  • 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. (abcam.com)
  • By generating peptides from intracellular antigens which are then presented to T cells, the ubiquitin/26S proteasome system plays a central role in the cellular immune response. (springer.com)
  • Consequently, the combination of a number of regulatory events tunes the proteasome system to gain maximal efficiency in the generation of peptides with regard to their quality and quantity. (springer.com)
  • Cerundolo, V, Kelly A., Elliott T, Trowsdale J, Townsend A (1995) Genes encoded in the major histocompatibility complex affecting the generation of peptides for TAP transport. (springer.com)
  • Evidence suggests that the key role of IPs may hinge on their impact on the repertoire of peptides associated to major histocompatibility complex (MHC) I molecules. (mcponline.org)
  • The catabolic mechanism in cells that makes the initial cleavages to generate most presented peptides is the proteasome. (jimmunol.org)
  • Peptides that will be embedded into the cleft of class I molecules are initially processed by the proteasome, a complex structure located in the cytoplasm. (prolekare.cz)
  • A major challenge of modern biology is to understand the networks of interacting genes regulating complex traits, and the subset of these genes that affect naturally occurring quantitative genetic variation. (biomedcentral.com)
  • Expression profiling is a powerful method for identifying networks of pleiotropic genes regulating complex traits, but the relationship between variation in transcript abundance among lines used to map QTLs and genes affecting variation in quantitative traits is complicated. (biomedcentral.com)
  • Advances in medicine, agriculture, and an understanding of adaptive evolution depend on discovering the genes that regulate these complex traits, and determining the genetic and molecular properties of alleles at loci that cause segregating genetic variation in natural populations. (biomedcentral.com)
  • B ) Cryo-EM characterization of the inhibitor-treated and in vitro assembled 20S proteasome intermediate (20S IM-I). The left panel ( B1 ) shows a raw micrograph of the 20S IM-I embedded in vitreous ice, and the right panels show the reference-free 2D averages of the 20S IM-I ( B2 , top) and the purified 20S mature particles ( B3 , top). (nih.gov)
  • Immuno- and constitutive proteasome crystal structures reveal differences in substrate and inhibitor specificity. (ebi.ac.uk)
  • An ATP-stabilized inhibitor of the proteasome is a component of the 1500-kDa ubiquitin conjugate-degrading complex. (biomedsearch.com)
  • We have purified a 250-kDa inhibitor of the proteasome and shown that it corresponds to CF-2. (biomedsearch.com)
  • The 125I-labeled inhibitor and purified proteasome formed a complex. (biomedsearch.com)
  • When CF-1, ATP, and Mg2+ were also present, the 125I-labeled inhibitor along with the proteasome formed a complex of 1500 kDa. (biomedsearch.com)
  • Lactacystin is a specific inhibitor of the proteasome and is a potent apoptosis inductor in resting peripheral B-CLL cells. (biomedsearch.com)
  • The purified 20S proteasome has activity towards fluorogenic substrates that are cleaved by trypsin or chymotrypsin, and is sensitive to lactacystin, a specific inhibitor of the proteasome. (usp.br)
  • The proteasome is a multicatalytic proteinase complex with a highly ordered ring-shaped 20S core structure. (nih.gov)
  • Brown MG, Driscoll J, Monaco JJ (1991) Structural and serological similarity of MHC linked LMP and proteasome (multicatalytic proteinase complex). (springer.com)
  • Cardozo C (1993) Catalytic components of the bovine pituitary multicatalytic proteinase complex (proteasome). (springer.com)
  • Mycobacterium tuberculosis (Mtb) possesses a proteasome system analogous to the eukaryotic ubiquitin-proteasome pathway. (nih.gov)
  • Proteasomes are multicatalitic and multisubunit endopeptidase complexes widely distributed in eukaryotic cells. (usp.br)
  • While all eukaryotes express the above-described constitutive proteasome (CP), gnathostomes (jawed vertebrates) also express another form of proteasome, the immunoproteasome (IP). (mcponline.org)
  • Immune cells and other cell types exposed to interferon gamma express a variant of the proteasome referred to as the immunoproteasome and differing in a few subunit components ( Figure 1 ) [1] . (prolekare.cz)
  • Cycling B-CLL cells are highly susceptible to inhibition of the proteasome: involvement of p27, early D-type cyclins, Bax, and caspase-dependent and -independent pathways. (biomedsearch.com)
  • In the present study, we investigated the effect of proteasome inhibition in proliferating B-CLL cells. (biomedsearch.com)
  • METHODS: The effect of proteasome inhibition was analyzed using thymidine incorporation, annexin V assays, and TUNEL staining. (biomedsearch.com)
  • CONCLUSION: Proteasome inhibition is highly effective in proliferating B-CLL cells and induces apoptosis using a caspase-dependent and -independent pathway. (biomedsearch.com)
  • To evaluate the effect of proteasome inhibition on the infectivity and intracellular development of L. chagasi , murine macropages were challenged with promastigotes from early stationary phase treated with lactacystin. (usp.br)
  • Formation of a survivin-XIAP complex promotes increased XIAP stability against ubiquitination/proteasomal destruction and synergistic inhibition of apoptosis, which is abolished in XIAP(-/-) cells. (umassmed.edu)
  • This gene encodes a member of the proteasome B-type family, also known as the T1B family, that is a 20S core beta subunit. (nih.gov)
  • PSMA3 (Proteasome Subunit Alpha 3) is a Protein Coding gene. (genecards.org)
  • This gene is located in the class II region of the MHC (major histocompatibility complex). (genecards.org)
  • PSMB8 (Proteasome Subunit Beta 8) is a Protein Coding gene. (genecards.org)
  • Proteasomal selection of multiprotein complexes recruited by LIM homeo" by Cenap Gungor, Naoko Taniguchi-Ishigaki et al. (umassmed.edu)
  • Neither α-HICA nor Leu altered the increased proteasome activity and atrogene expression observed with immobilization. (elsevier.com)
  • While proteasomes are found in many types of cells, immunoproteasomes are located primarily in immune system cells. (medlineplus.gov)
  • However, our knowledge about the molecular mechanisms governing the assembly and dynamics of these complexes in cells remains limited. (umassmed.edu)
  • However, the large number of potential mutations to evaluate, the necessity to induce mutations in a common inbred background, and the level of replication required to detect subtle effects [ 1 ] all limit the feasibility of systematic whole-genome mutagenesis screens for complex traits in higher eukaryotes. (biomedcentral.com)
  • Proteasomes are found inside all eukaryotes and archaea, and in some bacteria. (wikipedia.org)
  • In eukaryotes, proteasomes are located both in the nucleus and in the cytoplasm. (wikipedia.org)
  • In addition to constitutive proteasomes (CPs), which are found in all eukaryotes, jawed vertebrates also express immunoproteasomes (IPs). (mcponline.org)
  • Whereas proteasomes are found in all eukaryotes, the MHC appeared only in jawed vertebrates. (mcponline.org)
  • The ubiquitin proteasome system plays a pivotal role in controlling the cell cycle. (umn.edu)
  • 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. (frontiersin.org)
  • We show that the L.chagasi proteasome the trypsin-like activity is higher than the chymotrypsin-like. (usp.br)
  • The base of the proteasome regulatory particle exhibits ATP-dependent chaperone-like activity. (springer.com)
  • Casting decreased gastrocnemius mass, which was associated with both a reduction in protein synthesis and S6K1 phosphorylation as well as enhanced proteasome activity and increased atrogin-1 and MuRF1 mRNA. (elsevier.com)
  • Proteasome activity and atrogene mRNA content were at control levels after 14 days and not affected by either treatment. (elsevier.com)
  • The proteasome activity can be complemented in the cytosol by endopeptidases ( Figure 1 ) [1] , [2] . (prolekare.cz)
  • PSMA2 may have a potential regulatory effect on another component(s) of the proteasome complex through tyrosine phosphorylation. (abcam.com)
  • In the present work we have purified a 20S form of proteasome from Leishmania chagasi and partially characterized it. (usp.br)
  • One α-subunit and one β-subunit structure in half proteasome and full proteasome positions are shown in carton representation. (nih.gov)
  • Neddylation / AAA+ lid domain / HEAT repeats / RPN1/RPN2 N-terminal domain / 26S proteasome regulatory subunit RPN5 C-terminal domain / AAA-protein family signature. (pdbj.org)