| 1996 |
MECL-1 (LMP10/PSMB10) was identified as the third IFN-gamma-inducible proteasome beta-type subunit. Upon IFN-gamma stimulation, LMP10 (along with LMP2 and LMP7) is incorporated into proteasomes while constitutive counterparts (LMP9, LMP17, LMP19) are displaced; MECL-1 was shown to be the product of the previously cloned MECL-1 gene and to harbor most or all catalytic sites of the proteasome. |
2D gel electrophoresis of IFN-gamma-treated cell lysates, Northern blot, protein fractionation of proteasome complexes |
Journal of immunology |
High |
8786291
|
| 1997 |
The incorporation of MECL-1 (PSMB10) into the 20S proteasome requires LMP2; conversely, LMP2 incorporation is strongly enhanced by MECL-1. MECL-1 replaces the constitutive homologous subunit Z. This obligatory co-incorporation of MECL-1 and LMP2 occurs at the level of proteasome precursor formation, indicating concerted assembly of IFN-gamma-inducible subunits encoded inside and outside the MHC. |
Cotransfection experiments, immunoprecipitation of 20S proteasome complexes, Western blot analysis of subunit composition |
Proceedings of the National Academy of Sciences of the United States of America |
High |
9256419
|
| 1997 |
Mouse MECL-1 (PSMB10) and its constitutive homolog MC14 show reciprocal tissue expression: MECL-1 mRNA is highest in thymus, lymph nodes, and spleen, while MC14 predominates in tissues with low MECL-1. This reciprocal pattern mirrors that of LMP2/delta and LMP7/MB1 pairs, and the protein composition of purified 20S proteasomes from liver, thymus, and lung reflects this RNA expression. |
Northern blot analysis, 20S proteasome purification and subunit protein composition analysis from multiple tissues |
European journal of immunology |
High |
9174609
|
| 1999 |
The MECL-1 (PSMB10) active site is responsible for the trypsin-like activity of the proteasome. A catalytically inactive mutant MECL-1 (active-site mutation) was incorporated normally into cytosolic proteasomes, replacing the constitutive MC14 subunit, but its prosequence removal was incomplete (indicating autocatalytic processing). Absence of the MC14/MECL-1 active sites specifically abrogated trypsin-like proteolytic activity without affecting other catalytic activities, and cleavage specificity is conserved between mammalian and yeast proteasomes. |
Site-directed mutagenesis of catalytic residue, stable cell line generation, proteasome purification, peptidase activity assays |
FEBS letters |
High |
10413086
|
| 2000 |
Overexpression of all three immunoproteasome subunits (LMP2, LMP7, MECL-1/PSMB10) in triple transfectants markedly enhanced MHC class I-restricted presentation of the LCMV NP118 epitope. In vitro, immunoproteasomes generated higher amounts of 11- and 12-mer precursor fragments containing the NP118 epitope compared to constitutive proteasomes, demonstrating that MECL-1 inclusion alters antigen processing specificity. |
Triple transfection of immunosubunits, T cell epitope presentation assay, in vitro proteasome digestion assay with peptide fragment analysis |
Journal of immunology |
High |
10878350
|
| 2006 |
T cells from double knockout mice lacking both MECL-1 (PSMB10) and LMP7 hyperproliferate in vitro in response to polyclonal mitogens, with accelerated cell cycling in both CD4+ and CD8+ subsets. This hyperproliferation is not observed in single knockouts, and in vivo there are increased numbers of central memory CD8+ T cells, implicating immunoproteasomes in T cell proliferation control beyond MHC class I antigen processing. |
Double knockout mouse model, mitogen stimulation assay, flow cytometry for cell cycling and T cell subsets, in vivo phenotyping |
Journal of immunology |
High |
16547243
|
| 2011 |
Adenovirus E1A directly binds MECL-1 (PSMB10) through its N-terminal region and conserved region 3, while binding poorly to the constitutive β2 subunit. E1A causes downregulation of MECL-1 (and LMP2 and LMP7) expression induced by IFN-gamma, and this downregulation is mediated by reduced IFN-gamma-stimulated STAT1 phosphorylation. |
Co-immunoprecipitation, cotransfection, Western blot, binding domain mapping |
Virology |
Medium |
22018786
|
| 2012 |
LMP7 and MECL-1 (PSMB10) jointly regulate cytokine expression (IFN-gamma, IL-4, IL-10, IL-2Rβ, GATA3, and t-bet) in activated splenocytes, while other cytokines (IL-2, IL-13, TNF-alpha, IL-2Rα) are regulated by the proteasome independently of LMP7/MECL-1. |
LMP7/MECL1-null mouse, splenocyte activation with PMA/ionomycin, quantitative RT-PCR for cytokine mRNAs, lactacystin inhibitor treatment |
Pharmacology |
Medium |
22398747
|
| 2017 |
Knockout of immunoproteasome subunit β2i (PSMB10) in DOCA/salt hypertensive mice attenuates cardiac fibrosis and inflammation. Mechanistically, β2i KO inhibits IκBα/NF-κB and TGF-β1/Smad2/3 signaling pathways, reducing expression of collagen I, collagen III, α-SMA, IL-1β, IL-6, and TNF-α. |
β2i knockout mouse model, DOCA/salt hypertension model, echocardiography, histological staining, qRT-PCR, Western blot |
Biochemical and biophysical research communications |
Medium |
28478040
|
| 2018 |
PSMB10 (β2i/LMP10) promotes PTEN degradation and AKT1 activation in atrial tissue during angiotensin II stimulation, which activates IKKβ and drives ubiquitin-mediated IκBα degradation and NF-κB target gene expression (IL-1β, IL-6, NOX2, NOX4, CX43), leading to atrial fibrosis and reactive oxygen species production. PSMB10 KO mice are protected from Ang II-induced atrial fibrillation while AAV9-PSMB10 overexpression aggravates it. |
PSMB10 knockout mice, rAAV9-PSMB10 overexpression, Ang II infusion model, IKKβ inhibitor (IMD-0354), Western blot for pathway components, proteasome activity assay |
Hypertension |
High |
29507100
|
| 2018 |
LMP10 (PSMB10) promotes PTEN degradation and activation of AKT/IKK signaling in retinal cells during Ang II stimulation, leading to IκBα phosphorylation and degradation and NF-κB target gene activation, causing hypertensive retinopathy with increased vascular permeability, ROS production, and inflammation. |
LMP10 knockout mice, intravitreal rAAV2-LMP10 injection, IKKβ inhibitor (IMD-0354), pathological staining, proteasome trypsin-like activity assay, Western blot |
Redox biology |
High |
29499566
|
| 2019 |
PSMB10 interacts directly with classical swine fever virus NS3 protein (confirmed by Co-IP, GST pulldown, and confocal microscopy). PSMB10 overexpression inhibits CSFV replication and promotes ubiquitin-proteasome-dependent degradation of NS3. Additionally, PSMB10 restores MHC class I antigen presentation that CSFV had suppressed. |
Yeast two-hybrid screening, co-immunoprecipitation, GST pulldown, laser confocal microscopy, overexpression and knockdown of PSMB10, viral replication assay |
Virology |
High |
31493657
|
| 2019 |
Crystal structures of β2c- and β2i (PSMB10)-humanized yeast proteasomes with selective inhibitors LU-002c and LU-002i reveal significant differences in the substrate-binding channels of β2c and β2i that underlie subunit selectivity, enabling rational design of compounds with 40-45-fold selectivity for each subunit. |
X-ray crystallography of inhibitor-proteasome co-crystals, activity-based protein profiling, yeast mutagenesis, organic synthesis and biochemical screening |
Journal of medicinal chemistry |
High |
30657666
|
| 2020 |
LMP10 (PSMB10) deletion attenuates atherosclerosis in ApoE KO mice by shifting macrophage polarization toward M2 and reducing NF-κB activation (decreased IκBα degradation). Myeloid-specific deletion via bone marrow transplantation recapitulates this phenotype. In vitro, LMP10 deletion blunts macrophage polarization and ox-LDL-induced foam cell formation. |
LMP10 KO mice, ApoE KO atherosclerosis model, bone marrow transplantation, flow cytometry for macrophage polarization, in vitro macrophage culture, Western blot |
Frontiers in cell and developmental biology |
High |
33195259
|
| 2020 |
LMP10 (PSMB10) KO in Ang II-infused mice promotes autophagic degradation of IGF1R and gp130, reducing downstream phosphorylation of AKT, mTOR, STAT3, and ERK1/2, leading to attenuated cardiac hypertrophic remodeling. In vitro knockdown of LMP10 increases LC3II/I ratio (autophagy marker) and promotes IGF1R/gp130 degradation; chloroquine (autophagy inhibitor) reverses this effect. |
LMP10 KO mice, Ang II infusion, echocardiography, Western blot for signaling components, siRNA knockdown, autophagy inhibitor treatment |
Frontiers in physiology |
Medium |
32581853
|
| 2021 |
Triple knockout of all three immunoproteasome catalytic subunits (β1i/LMP2, β2i/MECL-1/PSMB10, β5i/LMP7) impairs control of Toxoplasma gondii infection, reducing dendritic cell, monocyte, and CD8+ T cell numbers, impairing IFN-gamma/TNF/iNOS production, altering T cell differentiation, elevating apoptosis of microglia and monocytes, and diminishing STAT3 downstream signaling. |
Triple immunoproteasome KO mice, T. gondii infection model, flow cytometry, STAT3 signaling analysis, cytokine measurement |
Frontiers in immunology |
Medium |
33968021
|
| 2023 |
β2i (PSMB10) KO in mice subjected to cardiac I/R injury results in excessive mitochondrial fission due to Mfn1/2 and Drp1 imbalance. Mechanistically, I/R reduces β2i expression and activity, which increases Parkin E3 ligase expression and promotes ubiquitin-dependent degradation of mitofusin 1/2 (Mfn1/2), causing mitochondrial fragmentation. Cardiac overexpression of β2i via rAAV9 ameliorates I/R injury. |
β2i KO mice, rAAV9-β2i overexpression, cardiac I/R model, electron microscopy for mitochondrial morphology, Western blot for Parkin/Mfn1/2/Drp1, infarct size measurement |
Cellular and molecular life sciences |
Medium |
37501008
|
| 2024 |
A heterozygous dominant-negative PSMB10 variant (G201R) markedly reduces immunoproteasome protein expression (PSMB9 and PSMB10) in PBMCs, EBV-B cells, and fibroblasts. PSMB10 is expressed in cortical and medullary thymic epithelial cell subsets (per scRNA-seq). The mutation impairs positive selection of CD8 T cells, generation of T cell receptor diversity, and negative selection of autoreactive T cells, causing severe combined immunodeficiency and Omenn syndrome. |
Immunoblotting, flow cytometry, artificial thymic organoid T-cell development assay, human thymus single-cell RNA sequencing, immunophenotyping |
The Journal of allergy and clinical immunology |
High |
39734035
|
| 2025 |
PSMB10 maintains stemness of chemotherapy-resistant leukemia stem cells by inhibiting senescence and cytotoxic T lymphocyte killing. Mechanistically, PSMB10 downregulation boosts SLC22A16-mediated drug endocytosis and induces chemotherapy-mediated senescence via the RPL6/RPS6-MDM2-P21 pathway. Additionally, PSMB10 promotes MHC-I protein degradation to enable immune escape from CTL killing. Genetic inactivation of PSMB10 in vivo reduces human LSC frequency 19-fold and drug-resistant mouse LSC frequency 7.6-fold. |
siRNA/lentivirus knockdown, co-immunoprecipitation, luciferase reporter assays, polysome profiling, quantitative proteomics, xenograft and syngeneic BMT mouse models, flow cytometry |
Journal of experimental & clinical cancer research |
High |
40462177
|
| 2026 |
A dominant-negative PSMB10 p.G209R mutation disrupts immunoproteasome assembly and function, leading to defective viral sensing and antigen presentation in IFN-treated fibroblasts, causing severe T lymphopenia at birth. Molecular modeling and biochemical studies confirmed impaired immunoproteasome assembly. Despite this, the patient recovered normal naïve T cell counts and T cell receptor diversity within the first year of life. |
Molecular modeling, proteomics, transcriptomics, ex vivo T lymphopoiesis, immunoproteasome assembly and function assays |
Journal of human immunity |
Medium |
41971628
|