ProteasomeInhibitorOral immunoproteasome inhibitorsSubunitsInhibitionPeptidesCylindrical protein complexSelectiveSubunitAntigenImmunologyConstitutiveProteinsInductionRegulatorImmuneDemonstrateCellsResultsRoleRole of the immunoproteasomeInhibitorSubunit of the immunoproteasomeExpression of the immunoproteasomeProteasome and the immunoproteasomeLMP7Target the immunoproteasomeConstitutive proteasomeInflammatoryLMP2Autoimmune diseasesInducibleAbundantly expressedPSMB9MiceCatalyticLungImmunoproteasomesInflammationIncreasesActivityImportant
Proteasome11
- An immunoproteasome is a type of proteasome that degrades ubiquitin-labeled proteins found in the cytoplasm in cells exposed to oxidative stress and proinflammatory stimuli. (wikipedia.org)
- In the classical proteasome, the beta (β) 1, β2 and β5 subunits have catalytic activity, which, however, in the immunoproteasome are replaced by the subunits LMP2 (alias β1i), MECL-1 (alias β2i), and LMP7 (alias β5i). (wikipedia.org)
- Apart from the normal, so-called "constitutive" proteasome, mammals also bear a specialized version, the immunoproteasome, which differs from its constitutive counterpart in the enzymatically active subunits. (mytum.de)
- Although the substrate binding pockets of both proteasome types are lined with almost identical amino acids, subtle changes in the immunoproteasome cause one particular methionine to adopt a different orientation than in the constitutive proteasome. (mytum.de)
- CRISPR/Cas9-mediated knockout experiments confirmed upregulation of the constitutive proteasome upon disruption of the immunoproteasome, protecting cells from death. (rcsb.org)
- Processing of some antigens by the standard proteasome but not by the immunoproteasome results in poor presentation by dendritic cells. (ox.ac.uk)
- Here, we demonstrate that interferon-α-mediated stimulation of the immunoproteasome, a proteasome isoform mainly present in immune cells and distinguished from the constitutive proteasome by virtue of its different catalytic β-subunits, as well as the proteasome activator 28 regulatory complex11-13, and the associated accelerated turnover of TRIM5α underpin the reprogramming of human TRIM5α for effective capsid-dependent inhibition of HIV-1 DNA synthesis and infection. (kcl.ac.uk)
- Since this treatment is known to induce the exchange of the three catalytic subunits of the proteasome to form the immunoproteasome, this result suggested that the processing of this MAGE-3 peptide required the immunoproteasome. (ox.ac.uk)
- Mass spectrometric analyses of in vitro digestions of a long precursor peptide with either proteasome type showed that the immunoproteasome produced the antigenic peptide more efficiently, whereas the standard proteasome more efficiently introduced cleavages destroying the antigenic peptide. (ox.ac.uk)
- An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. (nih.gov)
- Amniotic Fluid Proteasome and Immunoproteasome in the Setting of Intra-Amniotic Infection, Inflammation, and Preterm Birth. (uic.edu)
Inhibitor5
- It results in a larger pocket in the immunoproteasome, which therefore preferentially accommodates bulky amino acids and also the inhibitor. (mytum.de)
- ONX 0914, an immunoproteasome subunit LMP7 (β5i)-selective inhibitor, impeded the chronic rejection of kidneys transplanted from Fischer to allogeneic Lewis rats. (uni-konstanz.de)
- 2017. Structure of human immunoproteasome with a reversible and noncompetitive inhibitor that selectively inhibits activated lymphocytes. . (cornell.edu)
- Immunoproteasome inhibitor DPLG3 attenuates experimental colitis by restraining NF-κB activation. (cornell.edu)
- 2016. Brief treatment with a highly selective immunoproteasome inhibitor promotes long-term cardiac allograft acceptance in mice. . (cornell.edu)
Oral immunoproteasome inhibitors1
- On June 13, Principia joined AbbVie in announcing the start of an immunology collaboration designed to develop oral immunoproteasome inhibitors for an unspecified variety of immunological diseases. (genengnews.com)
Subunits1
- The concentrations of 31 candidate protein spots were potentially abnormal in HIV-infected decedents with HIV encephalitis and/or increased expression of immunoproteasome subunits. (elsevierpure.com)
Inhibition8
- However, inhibition of the immunoproteasome may alleviate disease symptoms and progression. (mytum.de)
- As in autoimmune diseases like rheumatism, type 1 diabetes and multiple sclerosis, as well as in certain types of cancer immunoproteasome levels are increased, inhibition of its activity might provide a rational therapeutic strategy. (mytum.de)
- Evaluation of these inhibitors revealed that immunoproteasome-specific inhibition does not lead to immune cell death as anticipated and that targeting viability requires inhibition of both immuno- and constitutive proteasomes. (rcsb.org)
- Thus, immunoproteasome inhibition alone is not a suitable approach to deplete immune cells. (rcsb.org)
- In contrast, immunoproteasome inhibition is effective in preclinical models of autoimmune diseases and was applied over weeks without obvious adverse side effects. (uni-konstanz.de)
- Selective immunoproteasome inhibition reduced the numbers of B and plasma cells, and suppressed donor-specific alloantibody production. (uni-konstanz.de)
- Thus, our studies define a critical role of the immunoproteasome in chronic kidney allograft rejection and suggest immunoproteasome inhibition as a promising therapeutic approach to suppress chronic antibody-mediated rejection. (uni-konstanz.de)
- Human papillomavirus E5 suppresses immunity via inhibition of the immunoproteasome and STING pathway. (ucsd.edu)
Peptides6
- The function of the immunoproteasome is primarily to specifically cleave proteins into shorter peptides, which can then be displayed on the cell surface together with the MHC I complex. (wikipedia.org)
- In order to expose a peptide on the cell surface, the ubiquitin-labeled protein, specifically cleaved into peptides by immunoproteasome, must first be transferred to the endoplasmic reticulum using TAP1 and TAP2 transporters and chaperones. (wikipedia.org)
- Like a shredder, the immunoproteasome cuts down proteins into peptides that are subsequently presented on the cellular surface. (mytum.de)
- Thus, the immunoproteasome generates more likely peptides that display high affinity for MHC-I receptors. (mytum.de)
- Processing of peptides for presentation to CD8(+) T cells may be critically dependent on the immunoproteasome, expression of which is affected by MCMV. (ox.ac.uk)
- However, the overall importance of the immunoproteasome in the generation of immunodominant peptides from MCMV is not known. (ox.ac.uk)
Cylindrical protein complex1
- Structurally, immunoproteasome is a cylindrical protein complex composed of a catalytic 20S subunit and a 19S regulatory subunit. (wikipedia.org)
Selective2
- However, so far, the lack of structural data on the immunoproteasome required tremendous efforts to develop selective compounds. (mytum.de)
- Here, we disclose the development of highly subunit-selective immunoproteasome inhibitors using insights obtained from the first bona fide human immunoproteasome cocrystal structures. (rcsb.org)
Subunit2
- Some examples where the effect of immunoproteasome on pathology has been confirmed are given below: Mutations in the PSMB8 gene, which encodes the LMP7 subunit, are involved in a variety of diseases and autoinflammatory disorders, the symptoms of which include skin rash, erythema, spiking fever and lipodystrophy, which are presented since early childhood. (wikipedia.org)
- In Alzheimer's disease, a single nucleotide polymorphisms have been found in the immunoproteasome subunit, which increases the chance of its occurrence. (wikipedia.org)
Antigen2
- Lack of cleavage by the immunoproteasome was also observed for melanoma differentiation antigen Melan-A26-35/HLA-A2, currently used for antitumoral vaccination. (ox.ac.uk)
- This is the first example of a tumor-specific antigen exclusively presented by tumor cells expressing the immunoproteasome. (ox.ac.uk)
Immunology1
- Professor Michael Groll, Chair of Biochemistry in the Department of Chemistry at the TU Muenchen and his co-worker, Eva Maria Huber, in collaboration with Professor Marcus Groettrup, Chair of Immunology at the University of Konstanz (Germany) and director of the Biotechnology Institute Thurgau (BITg) in Kreuzlingen (Switzerland), now achieved a milestone: Using X-ray crystallography, they elucidated the crystal structures of both, the constitutive and the immunoproteasome of mice. (mytum.de)
Constitutive1
- The crystal structures of the constitutive and immunoproteasome enabled Groll and Huber to identify the prerequisites for the high affinity of PR-957 for the immunoproteasome. (mytum.de)
Proteins1
- Gelman, BB & Nguyen, TP 2010, ' Synaptic proteins linked to HIV-1 infection and immunoproteasome induction: Proteomic analysis of human synaptosomes ', Journal of Neuroimmune Pharmacology , vol. 5, no. 1, pp. 92-102. (elsevierpure.com)
Induction2
- ONX 0914 inhibited immunoproteasome induction both in immune organs and renal allografts. (uni-konstanz.de)
- Immunoblots showed that the concentration of some of them was related to HIV-1 infection of the brain and immunoproteasome (IPS) induction. (elsevierpure.com)
Regulator1
- The immunoproteasome contains an alternate regulator, referred to as the 11S regulator or PA28, that replaces the 19S regulator. (antibodypedia.com)
Immune1
- An attractive alternative is to selectively inhibit the immune cell-specific immunoproteasome to deplete pathogenic immune cells and spare nonhematopoietic cells. (rcsb.org)
Demonstrate1
- Interestingly we found that memory "inflating" epitopes demonstrate reduced immunoproteasome dependence compared to non-inflating epitopes. (ox.ac.uk)
Cells1
- It is in amyloid plaques that the active activity of the immunoproteasome is found as a consequence of the cells' efforts to remove plaques. (wikipedia.org)
Results1
- The results are reported in the renowned journal "Cell" and will enable the development of new drugs that selectively target the immunoproteasome. (mytum.de)
Role2
Role of the immunoproteasome3
- We used mouse adenovirus type 1 (MAV-1) to characterize the role of the immunoproteasome in adenovirus pathogenesis. (duke.edu)
- Since the primary role of the immunoproteasome is to process antigens for presentation on major histocompatibility complex (MHC) class I molecules to CD8 + T lymphocytes, the immunoproteasome degrades various proteins, including viral proteins. (immune-system-research.com)
- One active project in my lab focuses on the role of the immunoproteasome in lung cancer progression. (uth.edu)
Inhibitor5
- A selective inhibitor of the immunoproteasome subunit LMP7 blocks cytokine production and attenuates progression of experimental arthritis. (immune-system-research.com)
- Crystal structure of the immunoproteasome of a mouse (Reproduced from Immuno- and constitutive proteasome crystal structures reveal differences in substrate and inhibitor specificity, Eva M. Huber et al. (psi.ch)
- Heart-Specific Immune Responses in an Animal Model of Autoimmune-Related Myocarditis Mitigated by an Immunoproteasome Inhibitor and Genetic Ablation. (uni-heidelberg.de)
- Zetomipzomib (KZR-616) is a first-in-class, selective and irreversible immunoproteasome inhibitor that results in anti-inflammatory activity in vitro and models of inflammatory conditions. (guidetopharmacology.org)
- 2017. Structure of human immunoproteasome with a reversible and noncompetitive inhibitor that selectively inhibits activated lymphocytes. . (cornell.edu)
Subunit of the immunoproteasome1
- LMP7 is the chymotrypsin-like subunit of the immunoproteasome. (immune-system-research.com)
Expression of the immunoproteasome2
- Interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) induce the expression of the immunoproteasome under inflammatory conditions, such as infections, and autoimmune diseases when inflammatory cytokines are present. (immune-system-research.com)
- We showed that there is heterogeneous expression of the immunoproteasome in lung cancer cell lines, and that this expression correlated with the epithelial-to-mesenchymal transition status of these cell lines, with more mesenchymal cell lines showing lower immunoproteasome expression. (uth.edu)
Proteasome and the immunoproteasome1
- Differential processing of class-I-restricted epitopes by the standard proteasome and the immunoproteasome. (ox.ac.uk)
LMP72
- Some examples where the effect of immunoproteasome on pathology has been confirmed are given below: Mutations in the PSMB8 gene, which encodes the LMP7 subunit, are involved in a variety of diseases and autoinflammatory disorders, the symptoms of which include skin rash, erythema, spiking fever and lipodystrophy, which are presented since early childhood. (wikipedia.org)
- 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)
Target the immunoproteasome1
- and will enable the development of new drugs that selectively target the immunoproteasome. (psi.ch)
Constitutive proteasome2
- The crystal structures of the constitutive proteasome and immunoproteasome enabled Groll and Huber to identify the prerequisites for the high affinity of PR-957 only for the immunoproteasome. (psi.ch)
- Although the substrate binding pockets of both proteasome types are lined with almost identically ordered amino acids, subtle changes in the immunoproteasome cause one particular methionine to adopt a different orientation than in the constitutive proteasome. (psi.ch)
Inflammatory3
- Thus, although immunoproteasome activity is robustly induced during acute infection with MAV-1, our data suggest that other mechanisms are capable of compensating for immunoproteasome activity to maintain antiviral immunity and appropriate inflammatory responses. (duke.edu)
- In addition, the immunoproteasome influences inflammatory disease pathogenesis through its ability to regulate T cell polarization. (immune-system-research.com)
- It remains unclear, however, how immunoproteasome dysfunction leads to inflammatory symptoms. (tokushima-u.ac.jp)
LMP21
- Inhibition of a secondary immunoproteasome subunit, in this case LMP2 is required to achieve a multicytokine inhibitory effect. (guidetopharmacology.org)
Autoimmune diseases2
- [ 4-6 ] In this review, we cover the diversity and relevance of constitutive and immunoproteasome subtypes in immune competent cells involved in autoimmune diseases, and provide an overview of several classes of reversible and irreversible PIs for therapeutic interventions. (medscape.com)
- The immunoproteasome is also expressed in nonimmune cell types during inflammation or neoplastic transformation, supporting a role in the pathogenesis of autoimmune diseases and neoplasms. (immune-system-research.com)
Inducible1
- inducible immunoproteasome. (bio-techne.com)
Abundantly expressed1
- Immunoproteasome is abundantly expressed in immune cells. (immune-system-research.com)
PSMB91
- The PSMB8 and PSMB9 immunoproteasome genes are essential in cell processes, such as decisions on cell survival or death, the cell cycle, and cellular differentiation. (nih.gov)
Mice1
- Following intranasal infection of mice, immunoproteasome activity in the heart and lung was significantly increased in an IFN-γ-dependent manner. (duke.edu)
Catalytic2
- Structurally, immunoproteasome is a cylindrical protein complex composed of a catalytic 20S subunit and a 19S regulatory subunit. (wikipedia.org)
- Expression of this gene is induced by gamma interferon and this gene product replaces catalytic subunit 1 (proteasome beta 6 subunit) in the immunoproteasome. (origene.com)
Lung1
- A similar phenomenon was observed in lung tumor samples, and tumors with lower immunoproteasome showed a more aggressive phenotype. (uth.edu)
Immunoproteasomes1
- This view has been challenged this year by reports showing that some epitopes, mainly of self origin, are not processed by the immunoproteasome and that mature dendritic cells constitutively express immunoproteasomes and therefore cannot efficiently present such epitopes. (ox.ac.uk)
Inflammation1
- The immunoproteasome also influences immune function by enhancing peptide presentation by MHC class I and promotes inflammation via IκB degradation and activation of NF-κB. (duke.edu)
Increases1
- In Alzheimer's disease, a single nucleotide polymorphisms have been found in the immunoproteasome subunit, which increases the chance of its occurrence. (wikipedia.org)
Activity2
- It is in amyloid plaques that the active activity of the immunoproteasome is found as a consequence of the cells' efforts to remove plaques. (wikipedia.org)
- Scholars@Duke publication: Interferon-dependent immunoproteasome activity during mouse adenovirus type 1 infection. (duke.edu)
Important1
- Therefore, the immunoproteasome plays an important role during viral infection. (immune-system-research.com)