• Mice
  • USP14 is a proteasome-associated DUB, and its ISG15 isopeptidase activity increases when complexed with the proteasome.By evolutionary standards, ISG15 is a newcomer among the UbLs and it apparently not only utilizes the conjugating but also the deconjugating machinery of its more established relative ubiquitin.Functional overlap between these two posttranslational modifiers might therefore be more extensive than previously appreciated and explain the rather innocuous phenotype of ISG15 mice. (nih.gov)
  • Further supporting a role for the proteasome in the Aβ and tau interaction is the data showing an impairment of proteasome activity in the 3×Tg-AD mice that correlates with an increase in Aβ oligomers . (nih.gov)
  • Remarkably, accumulation of Aβ and tau was found after direct inhibition of proteasome activity in the 3×Tg-AD mice . (nih.gov)
  • ubiquitin-proteasome
  • Increased expression of the ubiquitin-proteasome pathway in murine myotubes by proteolysis-inducing factor (PIF) is associated with activation of the transcription factor NF-kappaB. (nih.gov)
  • Coordinated regulation of nuclear receptor CAR by CCRP/DNAJC7, HSP70 and the ubiquitin-proteasome system. (nih.gov)
  • Proposed model for the regulation of CAR by the ubiquitin-proteasome system.An equilibrium between a stable CAR cytoplasmic complex (at top left) and a weaker associated complex exists (at top right), and HSP70 functions to favor the stable cytoplasmic complex. (nih.gov)
  • Many studies have identified the ubiquitin proteasome pathway (UPP) to be important for successful DENV production, but how the UPP contributes to DENV life cycle as host factors remains ill defined. (nih.gov)
  • A comprehensive framework of E2-RING E3 interactions of the human ubiquitin-proteasome system. (nih.gov)
  • The ubiquitin-proteasome system in Alzheimer's disease. (nih.gov)
  • Evidence has suggested that protein accumulation may result from a dysfunction in the ubiquitin proteasome system (UPS).Indeed, there is clear genetic and biochemical evidence of an involvement of the ubiquitin proteasome system in AD.This review summarizes the data supporting an involvement of the UPS in the pathogenesis of AD, focusing on the data showing the relationship between Abeta and tau, the two hallmark lesions of AD, and the UPS. (nih.gov)
  • Evidence has suggested that protein accumulation may result from a dysfunction in the ubiquitin proteasome system (UPS). (nih.gov)
  • Indeed, there is clear genetic and biochemical evidence of an involvement of the ubiquitin proteasome system in AD. (nih.gov)
  • Much of the early work leading up to the discovery of the ubiquitin proteasome system occurred in the late 1970s and early 1980s at the Technion in the laboratory of Avram Hershko, where Aaron Ciechanover worked as a graduate student. (wikipedia.org)
  • cytosolic
  • This results in the release of CAR from the cytosolic complex, followed by translocation into the nucleus. (nih.gov)
  • With increased CCRP expression and in concert with HSP70, a heteromeric protein complex that includes CAR, CCRP, and HSP70 is favored resulting in cytosolic stabilization of CAR. (nih.gov)
  • 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)
  • cathepsins
  • Antigen processing involves many proteolytic enzymes such as proteasomes and cathepsins. (nih.gov)
  • In this study, we examined the susceptibility of HIV-1 Env-A244 gp120 protein, one of the protein boost subunits of the RV144 Phase III vaccine trial, to proteasomes and cathepsins and identified the generated peptide epitope repertoire by mass spectrometry. (nih.gov)
  • Based on our results, the susceptibility of Env-A244 to cathepsins and not to proteasomes suggests a possible mechanism for the generation of Env-specific CD4(+)T cell and antibody responses in the RV144 vaccinees. (nih.gov)
  • proteolytic
  • Evidences of the crystal structures of isolated 20S proteasome complex demonstrate that the two rings of beta subunits form a proteolytic chamber and maintain all their active sites of proteolysis within the chamber. (wikipedia.org)
  • In an inactivated 20S proteasome complex, the gate into the internal proteolytic chamber are guarded by the N-terminal tails of specific alpha-subunit. (wikipedia.org)
  • eukaryotic cells
  • Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. (wikipedia.org)
  • Ricin B chain binds complex carbohydrates on the surface of eukaryotic cells containing either terminal N-acetylgalactosamine or beta-1,4-linked galactose residues. (wikipedia.org)
  • inactivation
  • In the early and mid 1970s two thiol-activated endopeptidases, responsible for more than 90% of bradykinin inactivation, were isolated from cytosol of rabbit brain, and characterized. (wikipedia.org)
  • Microscopy
  • Although electron microscopy data revealing the stacked-ring structure of the proteasome became available in the mid-1980s, the first structure of the proteasome core particle was not solved by X-ray crystallography until 1994. (wikipedia.org)
  • cells
  • CLDN1 is a major component in forming tight junction complexes between cells, which foster cell-cell adhesion of cell membranes. (wikipedia.org)
  • cytoplasm
  • Currently, it is known that in its inactive state, CAR is retained in the cytoplasm in a protein complex with HSP90 and the tetratricopeptide repeat protein cytosoplasmic CAR retention protein (CCRP). (nih.gov)
  • inhibit
  • During normal conditions, ubiquitinated tau is targeted to the proteasome for turnover (A). Aβ deposit can inhibit the proteasome impairing its normal function. (nih.gov)
  • contributes
  • Proteasome subunit beta type-10 is one of the 17 essential subunits (alpha subunits 1-7, constitutive beta subunits 1-7, and inducible subunits including beta1i, beta2i, beta5i) that contributes to the complete assembly of 20S proteasome complex. (wikipedia.org)
  • pathway
  • Env-A244 was resistant to proteasomes, thus diminishing the possibility of the generation of class I epitopes by the classical MHC class I pathway. (nih.gov)
  • protein complex
  • Type 2 RIPs consist of an A chain that is functionally equivalent to a type 1 RIP, covalently connected by a single disulfide bond to a B chain that is catalytically inactive, but serves to mediate transport of the A-B protein complex from the cell surface, via vesicle carriers, to the lumen of the endoplasmic reticulum (ER). (wikipedia.org)
  • activity
  • USP14 is a proteasome-associated DUB, and its ISG15 isopeptidase activity increases when complexed with the proteasome. (nih.gov)
  • Whereas type 1 RIPs are composed of a single protein chain that possesses catalytic activity, type 2 RIPs, also known as holotoxins, are composed of two different protein chains that form a heterodimeric complex. (wikipedia.org)