ArticleEMBO reports2018
Co-inhibition of immunoproteasome subunits LMP2 and LMP7 is required to block autoimmunity.
Article in EMBO reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 70 citations in OpenAlex.
- Intracellular Activation of Dual-Pharmacophore Artezomib Enhances Selective Cytotoxicity in Hematologic Malignancies.Journal of medicinal chemistry · 2026Article
- The immunoproteasome as a neuroimmune hub in the central nervous system: from proteostasis stress to inflammatory pathology.Journal of neuroinflammation · 2026Review
- α-Aminoboronic Acid Moieties in Boro Dipeptides Modulate Proteasome Subunit Selectivity and Provide Access to Compounds with Potent Anticancer and Anti-Inflammatory Activity.Journal of medicinal chemistry · 2025Article
- Immunoproteasome inhibition triggers protein stress and apoptosis in cells of B cell lineage without impairing vaccination-induced antibody responses.Cell death discovery · 2025Article
- Review
- Article
- Immunoproteasome Inhibition Impairs Differentiation but Not Survival of T Helper 17 Cells.Cells · 2025Article
- Novel insights into the molecular mechanisms of sepsis-associated acute kidney injury: an integrative study of GBP2, PSMB8, PSMB9 genes and immune microenvironment characteristics.BMC nephrology · 2025Article
- Recent Advances in the Development of Immunoproteasome Inhibitors as Anti-Cancer Agents: The Past 5 Years.Molecules (Basel, Switzerland) · 2025Review
- Effects of immunoproteasome inhibition on acute respiratory infection with murine hepatitis virus strain 1.Journal of virology · 2024Article
- Immunoproteasomal Inhibition With ONX-0914 Attenuates Atherosclerosis and Reduces White Adipose Tissue Mass and Metabolic Syndrome in Mice.Arteriosclerosis, thrombosis, and vascular biology · 2024Article
- Article
- Pharmacological induction of autophagy reduces inflammation in macrophages by degrading immunoproteasome subunits.PLoS biology · 2024Article
- Peripheral blood mononuclear cell low molecular mass protein 7 in acute ischemic stroke: vertical change from admission to discharge and correlation with disability, stroke recurrence, and death.Frontiers in immunology · 2024Article
- IFNɣ but not IFNα increases recognition of insulin defective ribosomal product-derived antigen to amplify islet autoimmunity.Diabetologia · 2023Article
- Molecular markers of type II alveolar epithelial cells in acute lung injury by bioinformatics analysis.Scientific reports · 2023Article
- Gastric cancer cell types display distinct proteasome/immunoproteasome patterns associated with migration and resistance to proteasome inhibitors.Journal of cancer research and clinical oncology · 2023Article
- The dichotomous role of immunoproteasome in cancer: Friend or foe?Acta pharmaceutica Sinica. B · 2023Review
- Immunoproteasome inhibition prevents progression of castration-resistant prostate cancer.British journal of cancer · 2023Article
- Suppression of prostate cancer and amelioration of the immunosuppressive tumor microenvironment through selective immunoproteasome inhibition.Oncoimmunology · 2023Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cells of hematopoietic origin express high levels of the immunoproteasome, a cytokine-inducible proteasome variant comprising the proteolytic subunits LMP2 (β1i), MECL-1 (β2i), and LMP7 (β5i). Targeting the immunoproteasome in pre-clinical models of autoimmune diseases with the epoxyketone inhibitor ONX 0914 has proven to be effective. ONX 0914 was previously described as a selective LMP7 inhibitor. Here, we show that PRN1126, developed as an exclusively LMP7-specific inhibitor, has limited effects on IL-6 secretion, experimental colitis, and experimental autoimmune encephalomyelitis (EAE). We demonstrate that prolonged exposure of cells with ONX 0914 leads to inhibition of both LMP7 and LMP2. Co-inhibition of LMP7 and LMP2 with PRN1126 and LMP2 inhibitors LU-001i or ML604440 impairs MHC class I cell surface expression, IL-6 secretion, and differentiation of naïve T helper cells to T helper 17 cells, and strongly ameliorates disease in experimental colitis and EAE. Hence, co-inhibition of LMP2 and LMP7 appears to be synergistic and advantageous for the treatment of autoimmune diseases.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.