ArticlePharmacology2012
A critical role for the inducible proteasomal subunits LMP7 and MECL1 in cytokine production by activated murine splenocytes.
Article in Pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 14 citations in OpenAlex.
- Trial
- Immunoproteasomal Inhibition With ONX-0914 Attenuates Atherosclerosis and Reduces White Adipose Tissue Mass and Metabolic Syndrome in Mice.Arteriosclerosis, thrombosis, and vascular biology · 2024Article
- Dysregulation of Gene Expression of Key Signaling Mediators in PBMCs from People with Type 2 Diabetes Mellitus.International journal of molecular sciences · 2023Article
- Reprograming of Gene Expression of Key Inflammatory Signaling Pathways in Human Peripheral Blood Mononuclear Cells by Soybean Lectin and Resveratrol.International journal of molecular sciences · 2022Article
- Review
- Article
- Inhibition of the immunoproteasome ameliorates experimental autoimmune encephalomyelitis.EMBO molecular medicine · 2014Article
- Activity-based imaging probes of the proteasome.Cell biochemistry and biophysics · 2013Review
- Proteasome protease mediated regulation of cytokine induction and inflammation.Biochimica et biophysica acta · 2012Review
- Activity-based near-infrared fluorescent probe for LMP7: a chemical proteomics tool for the immunoproteasome in living cells.Chembiochem : a European journal of chemical biology · 2012Article
- The Immunoproteasome in oxidative stress, aging, and disease.Critical reviews in biochemistry and molecular biologyReview
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Authors and funding
3 authors at 3 institutions in 1 country.
Funding
Abstract
background and purposeThe proteasome is a multi-subunit complex that proteolytically cleaves proteins. The replacement of the constitutive proteasome subunits β1, β2, and/or β5 with the IFNγ-inducible subunits LMP2, MECL1, and/or LMP7 results in the 'immunoproteasome'. The inducible subunits change the cleavage specificities of the proteasome, but it is unclear whether they have functions in addition to this. The purpose of the present study was to determine the role of the proteasome in general, as well as LMP7 and MECL1 specifically, with regard to cytokine production by activated primary splenocytes.
methodsA LMP7/MECL1-null mouse was engineered to determine the roles of these subunits in cytokine production. Isolated splenocytes from wild-type and LMP7/MECL1-/- mice were treated with lactacystin and activated with PMA and ionomycin and subsequently cytokine mRNA levels were quantified.
resultsThe present study demonstrates that LMP7/MECL1 regulates the expression of IFNγ, IL4, IL10, IL2Rβ, GATA3, and t-bet. In contrast, the regulation of IL2, IL13, TNFα, and IL2Rα by the proteasome appears to occur independently of LMP7/MECL1.
conclusionsCollectively, the present study demonstrates that LMP7 and MECL1 regulate cytokine expression, suggesting this system represents a novel mechanism for the regulation of cytokines and cytokine signaling.
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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.