• Alterations in autophagy and the ubiquitin proteasome system (UPS) are commonly implicated in protein aggregation and toxicity which manifest in a number of neurological disorders. (nih.gov)
  • Scholars@Duke publication: The cyclophilin-like domain of Ran-binding protein-2 modulates selectively the activity of the ubiquitin-proteasome system and protein biogenesis. (duke.edu)
  • The ubiquitin-proteasome system (UPS) plays a critical role in protein degradation. (duke.edu)
  • Such turnover occurs primarily through the ubiquitin-proteasome system and is central to a variety of cell regulatory mechanisms, many of medical relevance including many cancers. (yale.edu)
  • Much of this regulated degradation occurs via the highly conserved ubiquitin-proteasome system. (yale.edu)
  • The ubiquitin-proteasome system (UPS) plays a central role in various cellular processes through selectively degrading proteins involved in critical cellular functions. (nebraska.edu)
  • Molecular genetics of the ubiquitin-proteasome system: lessons from yeast. (huji.ac.il)
  • Dive into the research topics of 'Molecular genetics of the ubiquitin-proteasome system: lessons from yeast. (huji.ac.il)
  • The selective effect of CLD on the UPS in vivo is independent of, and synergistic with, proteasome inhibitors, and CLD does not affect the intrinsic proteolytic activity of the 20S proteasome. (duke.edu)
  • Further genetically engineered and in vitro selected clones resistant to proteasome inhibitors known to bind at the β4/β5 interface were cross-resistant to compound 1. (dundee.ac.uk)
  • Targeting UPS has been validated as a novel strategy for treating human cancer, as inhibitors of the 20S proteasome catalytic activity are currently in clinical use for treatment of multiple myeloma and other cancers, and the deubiquitinase activity associated with the proteasome is also a valid target for anticancer agents. (nebraska.edu)
  • Along the same lines, p53 is mostly degraded following the ubiquitin/proteasome pathway and calpains also seem to participate in its degradation. (cnrs.fr)
  • SOCS2 increases FLT3 ubiquitination and accelerates receptor degradation in proteasomes. (lu.se)
  • MHC class I ligands are recruited from the cytosolic peptide pool, whose size is likely to depend on the balance between peptide generation by the proteasome and peptide degradation by downstream peptidases. (elsevierpure.com)
  • The decrease in p27 Kip1 levels is the result of increased proteasome-dependent degradation, mediated and rate-limited by its specific ubiquitin ligase subunits S-phase kinase protein (Skp) 2 and cyclin-dependent kinase subunit (Cks) 1. (haifa.ac.il)
  • We cover some of the studies that show how proteasome degradation of protein aggregates, autophagy, mitophagy, and lysosomal function affect the quality control mechanisms required for neuronal survival. (houstonmethodist.org)
  • 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)
  • The proteasome is a molecular machine that fragments proteins into short peptides. (yale.edu)
  • The ubiquitin-proteasome pathway deconstructs most proteins in the eukaryotic cell cytosol and nucleus. (novusbio.com)
  • Taken together, our results suggest that, in response to systemic nicotine administration, the ubiquitin-proteasome, SUMO, and chaperonin complexes provide an intricate control mechanism to maintain cellular homeostasis, possibly by regulating the composition and signaling of target neurons in a region-specific manner. (bilkent.edu.tr)
  • The proteasome is a multicatalytic proteinase complex with a highly ordered ring-shaped 20S core structure. (nih.gov)
  • It consists of a 20S proteolytic core complex which is crowned at one or both ends by 19S regulatory subunit complexes. (novusbio.com)
  • Compounds that inhibit the function or proteolytic action of the PROTEASOME. (bvsalud.org)
  • Here we report that zinc pyrithione (ZnPT) targets the proteasome-associated DUBs (USP14 and UCHL5) and inhibits their activities, resulting in a rapid accumulation of protein-ubiquitin conjugates, but without inhibiting the proteolytic activities of 20S proteasomes. (nebraska.edu)
  • In the present report, we show that, after exposure to nicotine for 14 days, ubiquitin, ubiquitin-conjugating enzymes, 20S and 19S proteasomal subunits, and chaperonin-containing TCP-1 protein (CCT) complex members are upregulated in rat prefrontal cortex (PFC) while being downregulated in the medial basal hypothalamus (MBH). (bilkent.edu.tr)
  • Bassoon inhibits proteasome activity via interaction with PSMB4. (nih.gov)
  • Our primary current interest with the proteasome is its mechanism of assembly. (yale.edu)
  • 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)
  • Several genetic diseases are associated with defects in the ubiquitin-proteasome pathway. (novusbio.com)
  • The 26S proteasome is an ATP-dependent, multisubunit (~31), barrel-shaped molecular machine with an apparent molecular weight of ~2.5 MDa. (novusbio.com)
  • Comprehensive mode of action studies revealed that this compound primarily targets the T. cruzi proteasome, binding at the interface between β4 and β5 subunits that catalyse chymotrypsin-like activity. (dundee.ac.uk)
  • While proteasomes are found in many types of cells, immunoproteasomes are located primarily in immune system cells. (medlineplus.gov)
  • 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)
  • Proteasome beta-4 subunit contributes to the development of melanoma and is regulated by miR-148b. (nih.gov)
  • The 19S regulatory particle (RP) of the 26S proteasome mediates the recognition, deubiquitylation, unfolding, and channeling of ubiquitylated substrates to the 20S proteasome. (duke.edu)
  • Here, we show that ATF7IP is essential for SETDB1 stability: nuclear SETDB1 protein is degraded by the proteasome upon ablation of ATF7IP. (nih.gov)
  • Moreover, proteasome-dependent termination of signaling induced by one betac-engaging cytokine resulted in cellular desensitization to signal transduction by subsequent stimulation with another betac-engaging cytokine. (tamu.edu)
  • The proteasome core subcomplex that constitutes the two outer rings of the proteasome core complex. (mcw.edu)
  • An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. (nih.gov)
  • As a result, ATF7IP is critical for repression that requires H3K9 trimethylation by SETDB1, including transgene silencing by the HUSH complex. (nih.gov)
  • Demand on proteasome activity is increased in cancer cells, making them more sensitive to proteasome inhibition, and bortezomib and carfilzomib are used to treat certain hematological cancers. (nih.gov)
  • Proteasome Inhibition Sensitizes Liposarcoma to MDM2 Inhibition with Nutlin-3 by Activating the ATF4/CHOP Stress Response Pathway. (ucdenver.edu)
  • however, proteasome inhibition (PsmI) was also suggested by some experimental studies as a potential therapeutic strategy to curtail cardiac hypertrophy. (johnshopkins.edu)
  • Inhibition of the ubiquitin-proteasome pathway activates stress kinases and induces apoptosis in renal cancer cells. (elsevierpure.com)
  • The inhibition of the proteasome function can induce apoptosis in RCC irrespective of the VHL protein status. (elsevierpure.com)
  • Chickens, entrained to a 12-hour light-12-hour dark cycle, were assessed under various lighting conditions, in some cases after in vivo intravitreal administration of the protein synthesis inhibitor cycloheximide or lactacystin, an inhibitor of the 20S proteasome. (nih.gov)
  • This talk will focus on work done in the Walters lab to dissect how the proteasome recognizes its substrates and a new class of proteasome inhibitor that targets a 19S regulatory particle component. (nih.gov)
  • The mutant form of TTP was constitutively degraded by the proteasome and therefore expressed at low levels, yet it functioned as a potent mRNA destabilizing factor and inhibitor of the expression of many inflammatory mediators. (birmingham.ac.uk)
  • We therefore investigated the effectiveness of a proteasome inhibitor in the treatment of RCC regarding the involvement of Mitogen-activated protein kinases (MAP kinases), because MAP kinases are major signal transduction molecules that are known to play a pivotal role in cancer cell proliferation or apoptosis triggered by extra-cellular cytokines and growth factors. (elsevierpure.com)
  • A proteasome inhibitor, MG132 inhibited the proliferation of RCC cell lines, 786-O and KU20-01 in a time and dose-dependent manner. (elsevierpure.com)
  • This activity was inhibited by i) MG132, a reversible inhibitor of chymotrypsin and peptidylglutamyl peptidase hydrolase (PGPH) activities of the proteasome, ii) E64d, a permeable inhibitor of cysteine proteases and iii) TPCK, a serine chymotrypsin inhibitor, but not by epoxomicin, an irreversible and potent inhibitor of all enzymatic activities of the proteasome. (uandes.cl)
  • Immunoproteasome-mediated proteolysis generates immunogenic epitopes presented by major histocompatibility complex (MHC) class I molecules. (nih.gov)
  • Regulated protein proteolysis by the ubiquitin-proteasome system (UPS) is essential for cell cycle control, pathogen resistance, and protein quality control. (nih.gov)
  • Each layer of the UPS is highly controlled from substrate selection to proteolysis at the proteasome. (nih.gov)
  • Protein proteolysis occurs within a catalytic chamber of the 20S proteasome core particle while substrate recognition and processing takes place at a 19S regulatory particle which docks to either end of the 20S particle. (nih.gov)
  • CIT): Director's Seminar Series Regulated protein proteolysis by the ubiquitin-proteasome system (UPS) is essential for cell cycle control, pathogen resistance, and protein quality control. (nih.gov)
  • T (p.Thr75Met) in the proteasome subunit, beta-type, 8 (PSMB8) gene in affected patients from both pedigrees. (nih.gov)
  • weeks as evidenced by the dynamic changes in GFPdgn protein levels, proteasome peptidase activities, and total ubiquitin conjugates. (johnshopkins.edu)
  • From an analysis of a collection of cDNA and genomic clones, we identified a superfamily of 23 genes encoding all 14 of the Arabidopsis proteasome subunits, designated PAA-PAG and PBA-PBG for Proteasome Alpha and Beta subunits A-G, respectively. (wustl.edu)
  • We also analyzed the beta-subunits before and during assembly and reveal that those with longer propeptides are incorporated into half- and full proteasomes more rapidly than those that are heavily truncated. (ox.ac.uk)
  • Some of the subunits in Arabidopsis are found in forms that are independent of the complex. (tau.ac.il)
  • To characterize the preholoproteasome, formed by docking of two unprocessed half-proteasomes and not observed during assembly of wild type subunits, we trapped this intermediate using a beta-subunit mutational variant. (ox.ac.uk)
  • To learn whether the presence of such a domain near either end of a protein determines its direction of entry into the proteasome, directional translocation was enforced on several proteasome substrates. (huji.ac.il)
  • Human cytomegalovirus inhibits apoptosis by proteasome-mediated degrad" by Aiping Zhang, Richard L. Hildreth et al. (gwu.edu)
  • An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. (nih.gov)
  • Surprisingly, the direction of entry into the proteasome affected markedly the spectrum of peptides released and consequently influenced the efficiency of MHC class I presentation. (huji.ac.il)
  • Upon exposure to IFN-gamma, the standard proteasome is replaced by the immunoproteasome, which contains LMP2, LMP7 and MECL1, and is considered more efficient at producing antigenic peptides presented to CD8(+) T cells. (ox.ac.uk)
  • Here we investigated the function of the proteasome and other proteases in the process of intestinal regeneration using as a model the sea cucumber Holothuria glaberrima. (uandes.cl)
  • In pigmented cells, TYR is trafficked through those organelles rapidly, but in amelanotic cells, TYR is retained within the ER and is eventually degraded by proteasomes. (nih.gov)
  • The sum of these results shows that organellar pH, proteasome activity, and down-regulation of TYRP1 expression all contribute to the lack of pigmentation in TYR-positive amelanotic melanoma cells. (nih.gov)
  • Doses of 10 microM As(III) decreased cellular activity of the 20S proteasome by 40 and 15% in slices and HEK293 cells, respectively. (nih.gov)
  • While proteasomes are found in many types of cells, immunoproteasomes are located primarily in immune system cells. (medlineplus.gov)
  • The in vivo function status of the ubiquitin-proteasome system (UPS) in pressure overloaded hearts remains undefined. (johnshopkins.edu)
  • Differential processing of class-I-restricted epitopes by the standard proteasome and the immunoproteasome. (ox.ac.uk)
  • Here we describe the molecular organization of the 20S proteasome from the plant Arabidopsis thaliana. (wustl.edu)
  • NGL viewer: web-based molecular graphics for large complexes. (icr.ac.uk)
  • Structural Models for Interactions between the 20S proteasome and its PAN/19S activators. (cathdb.info)
  • Our in vitro work with pig gametes indicates that the sperm-borne 26S proteasomes selectively degrade an ubiquitinated ZP (glyco)protein during fertilization. (edu.au)
  • Polyubiquitin chain recognition activities associated with the sperm acrosomal proteasome could also contribute to anti-polyspermy control after sperm-egg fusion. (edu.au)
  • In the course of assembly, we observed formation of an early alpha/beta-heterodimer as well as an unprocessed half-proteasome particle. (ox.ac.uk)
  • The formation of the 20 S proteasome is a complex process that involves a cascade of folding, assembly, and processing events. (ox.ac.uk)
  • Three of the nine Arabidopsis proteasome subunit genes tested, PAC1 (α3), PAE1 (α5) and PBC2 (β3), could functionally replace their yeast orthologs, providing the first evidence for cross-species complementation of 20S subunit genes. (wustl.edu)
  • Taken together, these results demonstrate that the 20S proteasome is structurally and functionally conserved among eukaryotes and suggest that the subunit arrangement of the Arabidopsis 20S proteasome is similar if not identical to that recently determined for the yeast complex. (wustl.edu)
  • Kinesin Family Member 15 (KIF15) is a plus end-directed microtubule motor, which exerts complex regulations in cancer biology. (nih.gov)
  • The receptor tyrosine kinase (RTK) Ret is activated by the formation of a complex consisting of ligands such as glial cell line-derived neurotrophic factor (GDNF) and glycerophosphatidylinositol-anchored coreceptors termed GFRαs. (wustl.edu)
  • Formation of mature holoproteasomes occurred in concert with the disappearance of half-proteasomes. (ox.ac.uk)
  • We directly sequenced genes involved in immune response located in this critical region, excluding the HLA complex genes. (nih.gov)
  • The COP9 complex is essential for animal development. (tau.ac.il)