Affinage

PSMB9

Proteasome subunit beta type-9 · UniProt P28065

Length
219 aa
Mass
23.3 kDa
Annotated
2026-06-10
100 papers in source corpus 27 papers cited in narrative 27 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PSMB9 (LMP2/β1i) is an IFN-γ-inducible catalytic β subunit of the immunoproteasome that reshapes proteasomal peptide output to favor MHC class I antigen presentation (PMID:7937744, PMID:7583150). Synthesized as a ~24 kDa proprotein, it is processed within 13-16S precursor complexes and only the mature form is incorporated into 20S proteasomes (PMID:8120905, PMID:7829535). Upon incorporation it replaces the constitutive Y/δ subunit, suppressing cleavage after acidic residues while enhancing hydrolysis after basic residues in a dose-dependent manner; these opposing activities of Y and LMP2 account for the IFN-γ-induced shift in proteasome specificity (PMID:7937744, PMID:8663318). Its assembly into the 20S particle is mutually co-dependent with MECL-1, ensuring concerted incorporation of two immunosubunits at the precursor stage (PMID:9256419). Functionally, LMP2-containing proteasomes are selectively required to generate cytosolic precursor fragments for defined viral epitopes, and LMP2-deficient mice show reduced CD8+ T cell numbers and impaired CTL generation against influenza nucleoprotein (PMID:7600282, PMID:7583150, PMID:10878350). PSMB9 expression is coordinately regulated with TAP1 from a shared 593 bp bidirectional promoter, driven by IRF-1, a constitutive STAT1-IRF-1 complex, NF-κB (p50/p65), and Sp1, and is repressed by viral proteins (adenovirus E1A, HIV-1 Tat) that disrupt the STAT1-IRF-1 complex at the overlapping ICS-2/GAS element (PMID:7699330, PMID:8885869, PMID:10764778, PMID:16512786). Beyond antigen processing, PSMB9 supports broader proteostasis, controlling overall proteasome activity and limiting protein oxidation in vivo (PMID:16487046), modulating NF-κB-dependent gene expression including MMP-2/9 (PMID:16222703), mediating non-canonical IL-33 proteolysis (PMID:24619410), and being induced as a proteostasis defense during mitochondrial stress in an EEF1A2-dependent manner (PMID:37433777). A de novo PSMB9 p.G156D mutation causes a type I interferonopathy through a dominant-negative mechanism that destabilizes co-subunits PSMB8 and PSMB10 (PMID:33727065).

Mechanistic history

Synthesis pass · year-by-year structured walk · 25 steps
  1. 1994 High

    Established that LMP2 is a catalytic immunoproteasome subunit whose incorporation directly rewires proteasome cleavage specificity toward MHC class I-suitable peptides, rather than being merely a passive structural component.

    Evidence LMP2 transfection into lymphoblasts/HeLa cells with in vitro peptidase assays on purified 20S/26S proteasomes

    PMID:7937744

    Open questions at the time
    • Did not establish the in vivo consequence for antigen presentation
    • Did not resolve the structural basis of the cleavage shift
  2. 1993 Medium

    Showed that LMP2 is made as a 24 kDa proprotein and post-translationally processed during proteasome incorporation, defining a maturation requirement for catalytic activity.

    Evidence Pulse-chase and immunoblot in mouse T cells with cDNA/splice-form analysis

    PMID:7829535

    Open questions at the time
    • Did not identify the processing protease
    • Functional role of the two splice forms unresolved
  3. 1994 High

    Defined where processing occurs by showing LMP2 propeptide maturation happens within 13-16S precursor complexes and only mature forms enter active 20S particles.

    Evidence Pulse-chase and biochemical fractionation of precursor vs. mature complexes in mouse T cells

    PMID:8120905

    Open questions at the time
    • Assembly chaperones not identified
    • Order of subunit recruitment within precursors not fully resolved
  4. 1994 High

    Linked LMP2 biochemistry to immune function in vivo, demonstrating that LMP2 loss alters proteasome activity and reduces CD8+ T cell numbers and antigen-specific CTL precursor generation.

    Evidence LMP2 knockout mice with proteasome assays, T cell hybridoma stimulation, and CTL precursor frequency

    PMID:7600282

    Open questions at the time
    • Did not separate effects on proteasome activity from effects on T cell development
    • Specific epitope dependence not yet mapped
  5. 1995 High

    Confirmed selective LMP2 dependence of antigen presentation using gain- and loss-of-function in cells, showing LMP2 is specifically required for presentation of defined viral antigens.

    Evidence Antisense LMP2 RNA, IFN-γ transfection, and CTL assays in SP3 lymphoma and L929 fibroblasts

    PMID:7583150

    Open questions at the time
    • Generality across diverse epitopes not established
    • Did not address contribution of other immunosubunits
  6. 1995 High

    Resolved how LMP2 cooperates with regulators and other subunits, showing LMP2/LMP7 set cleavage-site preference while PA28/11S independently boosts peptide quality and quantity.

    Evidence In vitro digestion of 25-mer substrates with purified LMP-transfectant 20S ± PA28, HPLC/MS product analysis; IFN-γ-independent transfection with kinetic measurements

    PMID:7559557 PMID:7589133

    Open questions at the time
    • Substrate-specificity rules for endogenous antigens not generalized
    • Cooperativity mechanism between subunits not structurally defined
  7. 1996 High

    Pinpointed the molecular basis of the cleavage shift to subunit replacement, showing LMP2 and constitutive Y have opposing effects and LMP2 substitution suppresses postacidic cleavage.

    Evidence Transfection of X/Y subunit cDNAs into HeLa cells with peptidase and composition analyses

    PMID:8663318

    Open questions at the time
    • Atomic basis of substrate specificity difference not resolved
    • Contribution of X loss not fully separated from Y loss
  8. 1997 High

    Established a co-assembly rule whereby LMP2 and MECL-1 are mutually required for incorporation at the precursor stage, independent of LMP7.

    Evidence Co-transfection of LMP2 and MECL-1 with proteasome subunit composition analysis

    PMID:9256419

    Open questions at the time
    • Molecular signal coordinating their co-incorporation not identified
    • Stoichiometry of mixed/hybrid proteasomes not addressed
  9. 1995 High

    Defined the transcriptional architecture of PSMB9, showing TAP1 and LMP2 share a compact bidirectional promoter with NF-κB-driven cytokine induction and an Sp1/GC box for basal expression.

    Evidence Bidirectional reporters, mutagenesis, in vivo footprinting, and in vitro NF-κB/Sp1 DNA-binding studies

    PMID:7699330

    Open questions at the time
    • Did not address IFN-γ-specific elements
    • Cell-type-specific regulation not explored
  10. 1996 High

    Identified IRF-1 as the IFN-γ-responsive transcription factor required for coordinate TAP1/LMP2 upregulation, linking promoter occupancy to MHC class I surface expression and CD8+ T cell numbers.

    Evidence In vivo footprinting, EMSA, and IRF-1-deficient mice with MHC and CD8 readouts

    PMID:8885869

    Open questions at the time
    • Interplay with STAT1 at the same element not yet dissected
    • Did not separate direct vs. indirect IRF-1 effects
  11. 1997 Medium

    Connected promoter variation to disease susceptibility, showing a NOD-mouse promoter mutation ablates an Inr element and reduces both Lmp2 and Tap1 expression and proteasome activity.

    Evidence Sequencing, Northern blot, 5'-RACE, luciferase reporters, and proteasome activity assays of NOD vs. control promoters

    PMID:9300732

    Open questions at the time
    • Causal link to autoimmune phenotype not directly demonstrated
    • Effect specific to mouse strain context
  12. 2000 High

    Showed viral subversion of PSMB9 by demonstrating adenovirus E1A represses LMP2 transcription by sequestering IRF1 via STAT1 binding, disrupting the constitutive STAT1-IRF1 complex.

    Evidence E1A structure-function mutants, EMSA for complex disruption, and reporter assays

    PMID:10764778

    Open questions at the time
    • Did not quantify downstream impact on antigen presentation in infected cells
    • Other viral repressors not addressed
  13. 2000 High

    Demonstrated combinatorial enhancement of presentation, showing co-overexpression of LMP2/LMP7/MECL-1 markedly boosts presentation of an immunodominant epitope by generating more cytosolic precursor fragments.

    Evidence Triple transfection with CTL assays and in vitro substrate digestion/HPLC analysis

    PMID:10878350

    Open questions at the time
    • Relative contribution of each subunit not separated
    • Did not generalize beyond the tested epitope
  14. 2006 Medium

    Extended PSMB9 function to global proteostasis, showing LMP2 loss reduces multiple proteasome activities and increases oxidative protein damage in non-immune tissues.

    Evidence LMP2 knockout mice with fluorogenic activity assays and protein carbonyl measurements in brain and liver

    PMID:16487046

    Open questions at the time
    • Mechanism linking subunit loss to global activity not defined
    • Single lab
  15. 2006 Medium

    Defined an HIV-1 strategy paralleling E1A, with Tat repressing LMP2 by competing with STAT1 for IRF-1 at the ICS-2/GAS element.

    Evidence Reporter assays, EMSA/ChIP for STAT1-IRF-1 disruption, and proteasome activity assays

    PMID:16512786

    Open questions at the time
    • Functional impact on viral antigen presentation not quantified
    • Single lab
  16. 2006 Medium

    Implicated PSMB9 in NF-κB-driven matrix remodeling, showing LMP2 knockdown reduces IκBα degradation, p50 generation, and MMP-2/9 expression in trophoblasts.

    Evidence siRNA with RT-PCR, gelatin zymography, and cytosolic/nuclear fractionation Western blots

    PMID:16222703

    Open questions at the time
    • Direct substrate of LMP2 in NF-κB activation not identified
    • Single cell type
  17. 2006 Medium

    Linked stress-induced LMP2 to functional changes in antigen processing, showing heat shock transcriptionally upregulates lmp2/lmp7 and selectively enhances immunoproteasome-dependent epitope presentation.

    Evidence RT-PCR after heat shock and CTL assays with dependent vs. independent epitope controls

    PMID:17142736

    Open questions at the time
    • Transcription factors mediating heat-shock induction not identified
    • Single lab
  18. 2007 Medium

    Provided chemical-biology evidence that LMP2 catalytic activity has cell-intrinsic roles, with LMP2-selective irreversible inhibitors preferentially inhibiting growth of LMP2-rich cancer cells.

    Evidence Activity-based labeling with LMP2-selective probes and viability assays in LMP2+/- cancer lines

    PMID:17462577

    Open questions at the time
    • Substrates mediating growth effect unknown
    • Single lab
  19. 2010 Medium

    Refined the LMP2 phenotype mechanistically, showing immune defects in LMP2-/- mice track with altered NF-κB activity rather than impaired bulk protein degradation.

    Evidence LMP2 knockout mice with adoptive transfer, cytokine ELISAs, NF-κB activity assays, and flow cytometry

    PMID:20228196

    Open questions at the time
    • Direct NF-κB substrate of immunoproteasome not identified
    • Single lab
  20. 2014 Medium

    Identified a non-antigen-presentation proteolytic role, showing IFN-γ downregulates IL-33 protein through STAT1 and LMP2 in a caspase-independent manner.

    Evidence siRNA knockdown of LMP2/STAT1, adenoviral delivery, and Western blot for IL-33 in vitro and in vivo

    PMID:24619410

    Open questions at the time
    • Direct vs. indirect cleavage of IL-33 not established
    • Single lab
  21. 2014 Medium

    Confirmed PSMB9 has a structurally distinct active site by designing β1i-selective inhibitors using immunoproteasome crystal structures.

    Evidence Structure-based drug design from murine 20S X-ray structures with biochemical selectivity assays

    PMID:25006746

    Open questions at the time
    • Structural data from murine, not human, proteasome
    • Selectivity in cellular context not fully validated
  22. 2018 Medium

    Established that dual LMP2+LMP7 inhibition is required for therapeutic immunomodulation, showing LMP7-only blockade is insufficient to suppress autoimmunity.

    Evidence Selective inhibitors with IL-6 assays, MHC I and Th17 flow cytometry, and colitis/EAE models

    PMID:30279279

    Open questions at the time
    • Relative catalytic contribution of LMP2 vs. LMP7 not quantified
    • Single lab
  23. 2021 Medium

    Demonstrated PSMB9 causes human Mendelian disease, identifying a de novo p.G156D mutation that drives a type I interferonopathy through a dominant-negative mechanism destabilizing co-subunits.

    Evidence Whole-exome sequencing, patient LCL activity assays, and lentiviral transduction of mutant PSMB9 into normal LCLs with subunit Westerns

    PMID:33727065

    Open questions at the time
    • Mechanism linking proteasome dysfunction to interferon activation not defined
    • Single patient/lab
  24. 2021 Medium

    Placed PSMB9 upstream of Wnt/β-catenin signaling in vascular pathology, showing LMP2 inhibition restores blood-brain barrier integrity after ischemia in a β-catenin-dependent manner.

    Evidence Lentiviral LMP2 shRNA in MCAO/R rats, OGD/R cell models, β-catenin co-silencing epistasis, and permeability/tight-junction readouts

    PMID:34857032

    Open questions at the time
    • Mechanism connecting LMP2 to Wnt/β-catenin not molecularly defined
    • Single lab
  25. 2023 Medium

    Revealed a mitochondrial-stress proteostasis role, showing PSMB9 is upregulated as a defense response in an EEF1A2-dependent manner under mitochondrial dysfunction.

    Evidence Mitochondrial dysfunction models in human cells with proteomics, EEF1A2 siRNA, and proteasome activity assays

    PMID:37433777

    Open questions at the time
    • Mechanism of EEF1A2-dependent PSMB9 induction not defined
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • How non-antigen-presentation roles of PSMB9 (NF-κB regulation, IL-33 and IL-33-like substrate proteolysis, Wnt/β-catenin and mitochondrial-stress signaling) are mechanistically connected to its catalytic specificity remains unresolved.
  • Direct physiological substrates beyond MHC-precursor peptides not identified
  • Human structural model of the PSMB9 active site not established
  • Mechanism linking proteasome dysfunction to interferon hyperactivation unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 5 GO:0016787 hydrolase activity 3 GO:0005198 structural molecule activity 2
Localization
GO:0005829 cytosol 2
Pathway
R-HSA-168256 Immune System 4 R-HSA-392499 Metabolism of proteins 4 R-HSA-74160 Gene expression (Transcription) 4
Partners
EEF1A2IRF1MECL-1PSMB10PSMB8STAT1TAP1
Complex memberships
13-16S proteasome precursor compleximmunoproteasome 20S core particle

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 LMP2 (PSMB9) incorporation into 20S proteasomes alters peptidase activities: it reduces cleavage after acidic residues and increases hydrolysis after basic residues, without affecting hydrophobic activity. These changes are proportional to the amount of LMP2 incorporated and can account for the IFN-γ-induced shift in proteasome activity that favors generation of peptides with hydrophobic or basic C-termini for MHC class I presentation. Gene transfection of LMP2 into lymphoblasts or HeLa cells followed by in vitro peptidase activity assays on purified 20S and 26S proteasomes Proceedings of the National Academy of Sciences of the United States of America High 7937744
1994 LMP2-deficient mice have proteasomes with altered peptidase activities and antigen-presenting cells show reduced capacity to stimulate a T cell hybridoma specific for an H-2Db-restricted influenza nucleoprotein epitope. LMP2-/- mice also have ~60-70% of wild-type CD8+ T lymphocyte levels and generate 5- to 6-fold fewer influenza nucleoprotein-specific CTL precursors, indicating LMP2 influences antigen processing in vivo. Gene targeting (LMP2 knockout mice), purified proteasome peptidase assays, T cell hybridoma stimulation assay, CTL precursor frequency measurement Immunity High 7600282
1997 Incorporation of MECL-1 into the 20S proteasome is directly dependent on LMP2 (PSMB9) expression but independent of LMP7. Conversely, LMP2 uptake into proteasomes is strongly enhanced by MECL-1 co-expression. LMP2 and MECL-1 are mutually required for incorporation at the level of proteasome precursor formation, ensuring concerted assembly of two IFN-γ-inducible subunits. Co-transfection experiments with LMP2 and MECL-1 expression constructs, analysis of proteasome subunit composition Proceedings of the National Academy of Sciences of the United States of America High 9256419
1994 LMP2 (PSMB9) and LMP7 are synthesized as proproteins (~24 kDa and ~30 kDa respectively) and are processed within 13-16S proteasome precursor complexes; only their processed forms are incorporated into active 20S proteasomes. Pulse-chase experiments in mouse T cells, biochemical fractionation and analysis of 13-16S precursor complexes vs. mature 20S proteasomes Journal of molecular biology High 8120905
1995 LMP2+ proteasomes are specifically required for MHC class I-restricted presentation of influenza virus antigens. A T cell lymphoma (SP3) deficient only in LMP2 (among MHC-encoded antigen presentation genes) fails to present influenza antigens. Restoration of LMP2 expression (via IFN-γ transfection) rescues antigen presentation; antisense-LMP2 mRNA in IFN-γ-transfected SP3 cells or in LMP2-expressing L929 fibroblasts selectively represses presentation of the same antigens. Antisense RNA expression, IFN-γ gene transfection, CTL assays, analysis of selective LMP2 deficiency in SP3 lymphoma cells Current biology : CB High 7583150
1995 The PA28 (11S regulator) and LMP2/LMP7 subunits act together to govern peptide product profiles of 20S proteasomes in vitro. Incorporation of LMP2 and/or LMP7 changes cleavage site preference and peptide product quality from a 25-mer substrate. The 11S regulator does not preferentially activate LMP2- or LMP7-containing proteasomes but markedly changes both the quality and quantity of peptides produced when bound to any proteasome preparation. In vitro digestion of a 25-mer peptide substrate with purified 20S proteasomes from LMP transfectants ± purified PA28, product analysis by HPLC and electrospray mass spectrometry The Journal of biological chemistry High 7559557
1995 Incorporation of LMP2 (alone or with LMP7) into 20S proteasomes changes subunit stoichiometry, alters cleavage site preference, and changes the quality of peptides processed from a murine cytomegalovirus IE pp89 25-mer polypeptide substrate, independent of IFN-γ. Both LMP subunits together also induce a drastic increase in positive cooperativity (Hill coefficient) between proteasome subunits. IFN-γ-independent LMP transfection into murine fibroblasts, in vitro dual-cleavage digestion assays with purified 20S proteasomes, fluorogenic peptide substrate assays (Vmax, S0.5, Hill coefficient) European journal of immunology High 7589133
1996 LMP2 (PSMB9) and the constitutive subunit Y (delta) have opposing effects on proteasome peptidase activities: Y promotes cleavage after acidic residues while LMP2 suppresses it. Upon IFN-γ treatment, LMP2 replaces Y, thereby suppressing postacidic cleavage. Loss of Y by LMP2 incorporation accounts for suppression of postacidic cleavages, and loss of X contributes to increased hydrolysis after hydrophobic and basic residues. Transfection of X and Y subunit cDNAs into HeLa cells, peptidase activity assays, proteasome subunit composition analysis The Journal of biological chemistry High 8663318
1995 The human TAP1 and LMP2 genes are divergently transcribed from a shared bidirectional promoter of only 593 bp. The NF-κB element proximal to the TAP1 gene controls TNF-α induction of both TAP1 and LMP2; an adjacent GC box is required for basal expression of both genes and augments TNF-α induction. In vivo footprinting confirmed protein-DNA interactions at these sites; in vitro binding confirmed p50/p65 and p52/p65 heterodimers bind the NF-κB site, and Sp1 binds the GC box. Bidirectional reporter assays, site-specific mutagenesis, in vivo genomic footprinting, in vitro DNA-binding studies The Journal of experimental medicine High 7699330
1996 IRF-1 is required for IFN-γ up-regulation of both TAP1 and LMP2. In vivo footprinting shows IFN-γ increases protein-DNA contacts at an IRF-E element essential for up-regulation of both genes; gel shift analysis shows this site binds IRF-1. In IRF-1-deficient mice, TAP1 and LMP2 expression are both greatly reduced, surface class I MHC is reduced, and CD8+ T cells are reduced. In vivo footprinting, gel shift (EMSA), analysis of IRF-1-/- mice (KO phenotype), surface MHC and CD8 T cell measurement Immunity High 8885869
2000 Adenovirus E1A down-regulates LMP2 transcription by binding to Stat1 and interfering with the formation of the constitutive Stat1-IRF1 complex that normally occupies the overlapping ICS-2/GAS element of the LMP2 promoter. E1A sequesters IRF1 by occupying IRF1-binding domains on Stat1. The mutant E1A protein RG2 (binds Stat1 but not CBP/p300) also represses LMP2, while Delta2-36 (binds neither) does not, establishing that Stat1-binding is the key mechanism. E1A mutant analysis, EMSA/gel shift showing Stat1-IRF1 complex formation, reporter assays, protein-protein interaction studies The Journal of biological chemistry High 10764778
1993 LMP2 (PSMB9) is synthesized as a proprotein of 24 kDa; pulse-chase experiments demonstrate that the LMP2 polypeptide undergoes post-translational processing (from ~22.3 kDa to ~21.5 kDa) when incorporated into proteasomes. Two mRNA forms exist (LMP2.1 and LMP2.s resulting from alternative splicing of 30 bp from the first exon), yet both encode proteins processed to the same final size in proteasomes. Pulse-chase experiments, immunoblot with anti-recombinant LMP2.s antibodies, RT-PCR/cDNA sequence analysis The Journal of biological chemistry Medium 7829535
2000 Overexpression of all three immunoproteasome subunits (LMP2, LMP7, and MECL-1) together markedly enhances MHC class I presentation of the immunodominant LCMV NP118 epitope. In vitro, immunoproteasomes generate higher amounts of 11- and 12-mer precursor fragments containing NP118, consistent with cytosolic precursor generation for TAP transport. PA28 overexpression does not have a comparable effect on this epitope. Triple transfection of LMP2/LMP7/MECL-1, CTL presentation assays, in vitro digestion of substrate with HPLC product analysis Journal of immunology High 10878350
2006 LMP2-/- mice have reduced proteasome activities (chymotryptic, tryptic, and caspase-like) in both brain and liver, accompanied by increased levels of oxidatively damaged proteins in both tissues. This demonstrates that individual proteasome subunit (LMP2) expression regulates overall proteasome activity and protein oxidation in vivo. LMP2 knockout mice, proteasome activity assays (fluorogenic substrates), protein oxidation measurement (carbonyl content) in brain and liver tissue Antioxidants & redox signaling Medium 16487046
2006 HIV-1 Tat protein represses LMP2 transcription by competing with STAT1 for binding to IRF-1 on the overlapping ICS-2/GAS element of the LMP2 promoter. The constitutive LMP2 basal transcription depends on an unphosphorylated STAT1-IRF-1 complex at this element; intracellular Tat sequesters IRF-1, impairing complex formation and reducing LMP2 expression, with a consequent increase in proteolytic activity. Reporter assays, EMSA/ChIP to demonstrate STAT1-IRF-1 complex disruption by Tat, Western blot for LMP2 protein levels, proteasome activity assay The Biochemical journal Medium 16512786
2014 IFN-γ controls IL-33 protein levels through STAT1 and the LMP2 proteasome subunit. IFN-γ elevates LMP2 levels; siRNA-mediated silencing of LMP2 abrogates the IFN-γ-induced down-regulation of IL-33 protein, indicating LMP2 mediates non-canonical (non-antigen presentation) proteolysis of IL-33 in a caspase-independent fashion in pulmonary fibroblasts. siRNA knockdown of LMP2 and STAT1, pharmacological inhibition, adenoviral dual gene delivery, Western blot for IL-33 protein levels in vitro and in vivo The Journal of biological chemistry Medium 24619410
2006 LMP2 siRNA knockdown in the human invasive extravillous trophoblast cell line (HTR8/Svneo) suppresses MMP-2 and MMP-9 mRNA expression and activities. LMP2 contributes to IκBα degradation and p50 NF-κB subunit generation; inhibition of LMP2 reduces nuclear translocation of active NF-κB heterodimers, thereby reducing MMP-2 and MMP-9 expression. siRNA transfection, RT-PCR for MMP-2/9, gelatin zymography for MMP activity, Western blot for IκBα, p50, p65 in cytosolic and nuclear fractions, NF-κB inhibitor (SN50) control Journal of cellular physiology Medium 16222703
2010 LMP2-/- mice have mixed (hybrid) proteasomes in immune cells containing both standard and immunosubunits, and this compromises antiviral antibody responses, splenic B cell numbers, adoptively transferred B cell survival and function, Th cell function, and dendritic cell secretion of IL-6, TNF-α, IL-1β, and type I IFNs. These defects are associated with altered NF-κB activity rather than compromised overall protein degradation. LMP2 knockout mice, adoptive transfer experiments, cytokine measurements by ELISA, NF-κB activity assays, flow cytometry for immune cell populations Journal of immunology Medium 20228196
2018 Co-inhibition of LMP2 (β1i/PSMB9) and LMP7 (β5i) is required to block autoimmunity. Selective LMP7-only inhibition with PRN1126 has limited effects on IL-6 secretion, experimental colitis, and EAE. Prolonged ONX 0914 exposure inhibits both LMP7 and LMP2. Combined LMP7+LMP2 inhibition impairs MHC class I surface expression, IL-6 secretion, Th17 differentiation, and strongly ameliorates disease in colitis and EAE models. Selective inhibitors (PRN1126, LU-001i, ML604440, ONX 0914), cytokine assays (IL-6), flow cytometry for MHC I and Th17 cells, in vivo colitis and EAE models EMBO reports Medium 30279279
2021 A de novo PSMB9 p.G156D mutation causes a novel type I interferonopathy. Patient-derived B lymphoblastoid cell lines show reduced proteasome activities; exogenous transduction of mutant PSMB9 p.G156D into normal LCLs significantly suppresses proteasome activities and eliminates endogenous PSMB9 protein along with reduction of other immunoproteasome subunits PSMB8 and PSMB10, demonstrating a dominant-negative mechanism with co-subunit destabilization. Whole-exome sequencing, patient-derived LCL proteasome activity assays, lentiviral transduction of mutant PSMB9 into normal LCLs, Western blot for immunoproteasome subunit levels The Journal of allergy and clinical immunology Medium 33727065
2023 In human cells, mitochondrial dysfunction leads to upregulation of the immunoproteasome-specific subunit PSMB9 as a proteostasis defense response. PSMB9 expression under mitochondrial stress is dependent on the translation elongation factor EEF1A2. This defines a mode of proteasomal activation through change in proteasome composition driven by EEF1A2 and its spatial regulation. Mitochondrial dysfunction models in human cells, proteomics, siRNA knockdown of EEF1A2, Western blot for PSMB9 and other proteasome subunits, proteasome activity assays Nature communications Medium 37433777
2021 LMP2 (PSMB9) inhibition ameliorates ischemia/hypoxia-induced blood-brain barrier injury through activation of the Wnt/β-catenin signaling pathway. LMP2 knockdown in rat MCAO/reperfusion model restores tight junction proteins (occludin, claudin-1, ZO-1), increases microvascular density, and decreases BBB permeability. Co-silencing of β-catenin partially counteracted benefits of LMP2 silencing, establishing LMP2's pathway position upstream of Wnt/β-catenin. Lentivirus-mediated LMP2 shRNA in MCAO/R rat model, siRNA in OGD/R cell model, co-transfection with β-catenin siRNA, Western blot, Evans blue permeability assay, immunofluorescence Military Medical Research Medium 34857032
2006 PSMB9 (LMP2) knockdown in keratinocytes leads to significant suppression of TGF-β2 and TGF-β3, which are inducers of versican synthesis. IFN-γ stimulates PSMB9 expression in cultured keratinocytes. This places PSMB9 upstream of TGF-β2/β3 in the pathway regulating versican-mediated extracellular matrix composition in skin. siRNA knockdown of PSMB9 in keratinocytes, RT-PCR/Western blot for TGF-β2, TGF-β3, versican; IFN stimulation assays; proteomics of DM vs. healthy skin The British journal of dermatology Low 26713607
2014 Structure-based design identified β1i (PSMB9/LMP2)-selective inhibitors using X-ray structures of murine constitutive and immunoproteasome 20S core particles as templates. Cell-permeable compounds with selectivity for β1i over β5i and over constitutive β1c were developed, confirming that the PSMB9 active site has structural features distinct from other proteasome catalytic subunits. Structure-based drug design using X-ray crystal structures of 20S proteasome, synthesis and biochemical testing of inhibitors for selectivity and potency against individual subunits Journal of medicinal chemistry Medium 25006746
2007 LMP2-specific irreversible small molecule inhibitors selectively modify the LMP2/β1i subunit of the immunoproteasome with high specificity. LMP2-rich cancer cells are more sensitive to growth inhibition by the LMP2-specific inhibitor compared to LMP2-deficient cancer cells, implicating LMP2 catalytic activity in regulating cell growth of tumors that highly express it. Activity-based labeling with LMP2-selective inhibitors, cell viability assays comparing LMP2-expressing vs. LMP2-deficient cancer cell lines Chemistry & biology Medium 17462577
2006 Heat shock transcriptionally up-regulates lmp2 and lmp7 in mouse and human cells, and heat-shocked cells show enhanced presentation of immunoproteasome-dependent MHC class I epitopes (LCMV NP118-126, adenovirus E1B192-200) but not immunoproteasome-independent epitopes, demonstrating that heat shock-driven LMP2 induction functionally alters antigen processing. RT-PCR for lmp2/lmp7 mRNA after heat shock, CTL presentation assays for immunoproteasome-dependent vs. -independent epitopes Journal of immunology Medium 17142736
1997 In the NOD mouse, a T→A mutation in the shared bidirectional promoter of Lmp2 and Tap1 eliminates an initiator (Inr) element in the Lmp2 orientation, reduces Lmp2 and Tap1 mRNA levels, eliminates a Lmp2 transcription start site, and reduces proteasome peptide substrate activity. This promoter mutation thus reduces both Lmp2 and Tap1 gene expression. Sequencing of NOD vs. Balb/c promoter, Northern blot, 5'-RACE, luciferase reporter assays with NOD promoter construct, proteasome activity assay Journal of immunology Medium 9300732

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1992 Epstein-Barr virus latent gene transcription in nasopharyngeal carcinoma cells: coexpression of EBNA1, LMP1, and LMP2 transcripts. Journal of virology 428 1313894
1994 Altered peptidase and viral-specific T cell response in LMP2 mutant mice. Immunity 364 7600282
1994 Peptidase activities of proteasomes are differentially regulated by the major histocompatibility complex-encoded genes for LMP2 and LMP7. Proceedings of the National Academy of Sciences of the United States of America 277 7937744
2012 The role of the EBV-encoded latent membrane proteins LMP1 and LMP2 in the pathogenesis of nasopharyngeal carcinoma (NPC). Seminars in cancer biology 265 22249143
1994 An integral membrane protein (LMP2) blocks reactivation of Epstein-Barr virus from latency following surface immunoglobulin crosslinking. Proceedings of the National Academy of Sciences of the United States of America 212 8290598
1995 Coordinate regulation of the human TAP1 and LMP2 genes from a shared bidirectional promoter. The Journal of experimental medicine 208 7699330
1995 The interferon-gamma-inducible 11 S regulator (PA28) and the LMP2/LMP7 subunits govern the peptide production by the 20 S proteasome in vitro. The Journal of biological chemistry 202 7559557
2006 Immunoproteasome and LMP2 polymorphism in aged and Alzheimer's disease brains. Neurobiology of aging 178 16298241
1997 The subunits MECL-1 and LMP2 are mutually required for incorporation into the 20S proteasome. Proceedings of the National Academy of Sciences of the United States of America 171 9256419
1992 Consistent transcription of the Epstein-Barr virus LMP2 gene in nasopharyngeal carcinoma. Journal of virology 158 1313931
1993 HLA A2.1-restricted cytotoxic T cells recognizing a range of Epstein-Barr virus isolates through a defined epitope in latent membrane protein LMP2. Journal of virology 149 7693972
1990 A second Epstein-Barr virus membrane protein (LMP2) is expressed in latent infection and colocalizes with LMP1. Journal of virology 144 2157888
1995 Incorporation of major histocompatibility complex--encoded subunits LMP2 and LMP7 changes the quality of the 20S proteasome polypeptide processing products independent of interferon-gamma. European journal of immunology 141 7589133
1994 20 S proteasomes are assembled via distinct precursor complexes. Processing of LMP2 and LMP7 proproteins takes place in 13-16 S preproteasome complexes. Journal of molecular biology 129 8120905
2000 Transcriptional regulation of the major histocompatibility complex (MHC) class I heavy chain, TAP1 and LMP2 genes by the human papillomavirus (HPV) type 6b, 16 and 18 E7 oncoproteins. Oncogene 127 11039910
1996 Proteasome subunits X and Y alter peptidase activities in opposite ways to the interferon-gamma-induced subunits LMP2 and LMP7. The Journal of biological chemistry 126 8663318
1996 Regulation of LMP2 and TAP1 genes by IRF-1 explains the paucity of CD8+ T cells in IRF-1-/- mice. Immunity 123 8885869
1998 Analysis of major histocompatibility complex class I, TAP expression, and LMP2 epitope sequence in Epstein-Barr virus-positive Hodgkin's disease. Blood 118 9746788
2011 A phase II study evaluating the safety and efficacy of an adenovirus-ΔLMP1-LMP2 transduced dendritic cell vaccine in patients with advanced metastatic nasopharyngeal carcinoma. Annals of oncology : official journal of the European Society for Medical Oncology 117 21821548
1993 The last seven transmembrane and carboxy-terminal cytoplasmic domains of Epstein-Barr virus latent membrane protein 2 (LMP2) are dispensable for lymphocyte infection and growth transformation in vitro. Journal of virology 103 8383224
2000 Overexpression of the proteasome subunits LMP2, LMP7, and MECL-1, but not PA28 alpha/beta, enhances the presentation of an immunodominant lymphocytic choriomeningitis virus T cell epitope. Journal of immunology (Baltimore, Md. : 1950) 96 10878350
2007 LMP2-specific inhibitors: chemical genetic tools for proteasome biology. Chemistry & biology 95 17462577
1995 Association of LMP2 and LMP7 genes within the major histocompatibility complex with insulin-dependent diabetes mellitus: population and family studies. American journal of human genetics 91 7847389
1995 LMP2+ proteasomes are required for the presentation of specific antigens to cytotoxic T lymphocytes. Current biology : CB 88 7583150
2010 Unexpected role for the immunoproteasome subunit LMP2 in antiviral humoral and innate immune responses. Journal of immunology (Baltimore, Md. : 1950) 87 20228196
2000 Epstein-Barr virus latency: LMP2, a regulator or means for Epstein-Barr virus persistence? Advances in cancer research 87 10818681
2021 Inhibition of the immunoproteasome LMP2 ameliorates ischemia/hypoxia-induced blood-brain barrier injury through the Wnt/β-catenin signalling pathway. Military Medical Research 84 34857032
2014 Structure-based design of β1i or β5i specific inhibitors of human immunoproteasomes. Journal of medicinal chemistry 83 25006746
2004 The generation and characterization of LMP2-specific CTLs for use as adoptive transfer from patients with relapsed EBV-positive Hodgkin disease. Journal of immunotherapy (Hagerstown, Md. : 1997) 81 15235393
1994 MHC-encoded proteasome subunits LMP2 and LMP7 are not required for efficient antigen presentation. Journal of immunology (Baltimore, Md. : 1950) 80 8301122
2004 Adoptive transfer of allogeneic Epstein-Barr virus (EBV)-specific cytotoxic T cells with in vitro antitumor activity boosts LMP2-specific immune response in a patient with EBV-related nasopharyngeal carcinoma. Annals of oncology : official journal of the European Society for Medical Oncology 78 14679129
1994 PRE3, highly homologous to the human major histocompatibility complex-linked LMP2 (RING12) gene, codes for a yeast proteasome subunit necessary for the peptidylglutamyl-peptide hydrolyzing activity. FEBS letters 76 7907993
2000 Loss of interferon-gamma inducibility of TAP1 and LMP2 in a renal cell carcinoma cell line. Cancer research 71 11059775
2018 Co-inhibition of immunoproteasome subunits LMP2 and LMP7 is required to block autoimmunity. EMBO reports 68 30279279
2015 Latent Membrane Protein 2 (LMP2). Current topics in microbiology and immunology 68 26428374
2007 Cis- and trans-acting elements regulate the mouse Psmb9 meiotic recombination hotspot. PLoS genetics 66 17590084
2012 A selective inhibitor of the immunoproteasome subunit LMP2 induces apoptosis in PC-3 cells and suppresses tumour growth in nude mice. British journal of cancer 64 22677907
1997 IFN-gamma-mediated coordinated transcriptional regulation of the human TAP-1 and LMP-2 genes in human renal cell carcinoma. Clinical cancer research : an official journal of the American Association for Cancer Research 62 9815722
2004 Regulation of murine Tap1 and Lmp2 genes in macrophages by interferon gamma is mediated by STAT1 and IRF-1. Genes and immunity 61 14735146
1993 The major-histocompatibility-complex-encoded beta-type proteasome subunits LMP2 and LMP7. Evidence that LMP2 and LMP7 are synthesized as proproteins and that cellular levels of both mRNA and LMP-containing 20S proteasomes are differentially regulated. European journal of biochemistry 61 8365398
2010 Immunoproteasome LMP2 60HH variant alters MBP epitope generation and reduces the risk to develop multiple sclerosis in Italian female population. PloS one 55 20174631
2013 Epigenetic deregulation of the LMP1/LMP2 locus of Epstein-Barr virus by mutation of a single CTCF-cohesin binding site. Journal of virology 53 24257606
1995 Sequence polymorphism in the Epstein-Barr virus latent membrane protein (LMP)-2 gene. The Journal of general virology 53 7844523
2006 LMP2 knock-out mice have reduced proteasome activities and increased levels of oxidatively damaged proteins. Antioxidants & redox signaling 52 16487046
2006 Intracellular HIV-1 Tat protein represses constitutive LMP2 transcription increasing proteasome activity by interfering with the binding of IRF-1 to STAT1. The Biochemical journal 47 16512786
2010 PSMB8 (LMP7) but not PSMB9 (LMP2) gene polymorphisms are associated to pigeon breeder's hypersensitivity pneumonitis. Respiratory medicine 44 20153157
2006 Immunoproteasome subunit LMP2 expression is deregulated in Sjogren's syndrome but not in other autoimmune disorders. Annals of the rheumatic diseases 44 16414974
2023 Immunoproteasome-specific subunit PSMB9 induction is required to regulate cellular proteostasis upon mitochondrial dysfunction. Nature communications 42 37433777
2016 The Safety and Immunological Effects of rAd5-EBV-LMP2 Vaccine in Nasopharyngeal Carcinoma Patients: A Phase I Clinical Trial and Two-Year Follow-Up. Chemical & pharmaceutical bulletin 42 27477649
2017 Novel Epstein-Barr virus-like particles incorporating gH/gL-EBNA1 or gB-LMP2 induce high neutralizing antibody titers and EBV-specific T-cell responses in immunized mice. Oncotarget 41 27926486
1995 Polymorphism in the LMP2 gene influences susceptibility to extraspinal disease in HLA-B27 positive individuals with ankylosing spondylitis. Annals of the rheumatic diseases 41 7763114
2014 IFN-γ directly controls IL-33 protein level through a STAT1- and LMP2-dependent mechanism. The Journal of biological chemistry 39 24619410
2000 Adenovirus E1A down-regulates LMP2 transcription by interfering with the binding of stat1 to IRF1. The Journal of biological chemistry 38 10764778
1994 Presentation of viral antigens restricted by H-2Kb, Db or Kd in proteasome subunit LMP2- and LMP7-deficient cells. European journal of immunology 38 8056044
2021 Successful treatment of a novel type I interferonopathy due to a de novo PSMB9 gene mutation with a Janus kinase inhibitor. The Journal of allergy and clinical immunology 36 33727065
1996 Markedly decreased expression of TAP1 and LMP2 genes in HLA class I-deficient human tumor cell lines. Immunology letters 36 8803612
2023 A lipid-based LMP2-mRNA vaccine to treat nasopharyngeal carcinoma. Nano research 34 36618068
2015 Chimerically fused antigen rich of overlapped epitopes from latent membrane protein 2 (LMP2) of Epstein-Barr virus as a potential vaccine and diagnostic agent. Cellular & molecular immunology 34 25864917
2006 The mutation in the ATP-binding region of JAK1, identified in human uterine leiomyosarcomas, results in defective interferon-gamma inducibility of TAP1 and LMP2. Oncogene 33 16474838
2004 Expression of HLA class I antigen and proteasome subunits LMP-2 and LMP-10 in primary vs. metastatic breast carcinoma lesions. International journal of oncology 32 15547699
2000 LMP2 polymorphism is associated with extraspinal disease in HLA-B27 negative Caucasian and Mexican Mestizo patients with ankylosing spondylitis. The Journal of rheumatology 32 10648037
1997 The LMP2 polymorphism is associated with susceptibility to acute anterior uveitis in HLA-B27 positive juvenile and adult Mexican subjects with ankylosing spondylitis. Annals of the rheumatic diseases 32 9306872
2006 A structural model of 20S immunoproteasomes: effect of LMP2 codon 60 polymorphism on expression, activity, intracellular localisation and insight into the regulatory mechanisms. Biological chemistry 31 16606340
2006 Heat shock up-regulates lmp2 and lmp7 and enhances presentation of immunoproteasome-dependent epitopes. Journal of immunology (Baltimore, Md. : 1950) 31 17142736
1993 Molecular basis of genetic polymorphism in major histocompatibility complex-linked proteasome gene (Lmp-2). Proceedings of the National Academy of Sciences of the United States of America 31 7681985
2006 Dextran sulfate sodium-induced colitis is associated with enhanced low molecular mass polypeptide 2 (LMP2) expression and is attenuated in LMP2 knockout mice. Digestive diseases and sciences 30 16944024
2016 The role of PSMB9 upregulated by interferon signature in the pathophysiology of cutaneous lesions of dermatomyositis and systemic lupus erythematosus. The British journal of dermatology 29 26713607
2006 Proteasome subunit LMP2 is required for matrix metalloproteinase-2 and -9 expression and activities in human invasive extravillous trophoblast cell line. Journal of cellular physiology 29 16222703
1997 No independent associations of LMP2 and LMP7 polymorphisms with susceptibility to develop IDDM. Diabetes 29 9000709
1997 Reduced expression of Tap1 and Lmp2 antigen-processing genes in the nonobese diabetic (NOD) mouse due to a mutation in their shared bidirectional promoter. Journal of immunology (Baltimore, Md. : 1950) 29 9300732
1995 Polymorphism in the LMP2 gene influences the relative risk for acute anterior uveitis in unselected patients with ankylosing spondylitis. Clinical and investigative medicine. Medecine clinique et experimentale 29 7768065
2011 Potential role of LMP2 as tumor-suppressor defines new targets for uterine leiomyosarcoma therapy. Scientific reports 28 22355695
1993 Genomic organization of the mouse Lmp-2 gene and characteristic structure of its promoter. Gene 28 7901128
1997 Evolution of proteasome subunits delta and LMP2: complementary DNA cloning and linkage analysis with MHC in lower vertebrates. Journal of immunology (Baltimore, Md. : 1950) 26 9218589
1995 Major histocompatibility-encoded human proteasome LMP2. Genomic organization and a new form of mRNA. The Journal of biological chemistry 26 7829535
2023 LMP2-mRNA lipid nanoparticle sensitizes EBV-related tumors to anti-PD-1 therapy by reversing T cell exhaustion. Journal of nanobiotechnology 25 37679769
1999 Association of the large multifunctional proteasome (LMP2) gene with Graves' disease is a result of linkage disequilibrium with the HLA haplotype DRB1*0304-DQB1*02-DQA1*0501. Clinical endocrinology 24 10468973
1997 The MHC-encoded TAP1/LMP2 bidirectional promoter is down-regulated in highly oncogenic adenovirus type 12 transformed cells. FEBS letters 24 9001385
1996 Polymorphism in the LMP2 gene influences disease susceptibility and severity in HLA-B27 associated juvenile rheumatoid arthritis. The Journal of rheumatology 24 8730138
2004 Inhibition of apoptosis in acute promyelocytic leukemia cells leads to increases in levels of oxidized protein and LMP2 immunoproteasome. Proceedings of the National Academy of Sciences of the United States of America 23 15284441
2003 Immunoproteasome subunits LMP2 and LMP7 downregulation in primary malignant melanoma lesions: association with lack of spontaneous regression. Melanoma research 23 12883363
1996 Molecular analysis of a recombinational hotspot adjacent to Lmp2 gene in the mouse MHC: fine location and chromatin structure. Mammalian genome : official journal of the International Mammalian Genome Society 23 8672125
2023 Increased expression of the immunoproteasome subunits PSMB8 and PSMB9 by cancer cells correlate with better outcomes for triple-negative breast cancers. Scientific reports 22 36746983
2001 Systemic deficits in transporter for antigen presentation (TAP)-1 or proteasome subunit LMP2 have little or no effect on tumor incidence. International journal of cancer 22 11169961
1999 Selective amino acid substitutions of a subdominant Epstein-Barr virus LMP2-derived epitope increase HLA/peptide complex stability and immunogenicity: implications for immunotherapy of Epstein-Barr virus-associated malignancies. European journal of immunology 22 10458773
1993 Genomic organization and tissue expression of mouse proteasome gene Lmp-2. Genomics 22 8325639
1997 Polymorphism of the LMP2 gene and disease phenotype in ankylosing spondylitis: no association with disease severity. Clinical rheumatology 21 9348140
2023 Deciphering the tumor-suppressive role of PSMB9 in melanoma through multi-omics and single-cell transcriptome analyses. Cancer letters 20 37944578
2002 LMP2 and LMP7 gene polymorphism in Mexican populations: Mestizos and Amerindians. Genes and immunity 20 12209365
1996 Molecular and serological analysis of polymorphisms in the murine major histocompatibility complex-encoded proteasome subunits, LMP-2 and LMP-7. Experimental and clinical immunogenetics 20 8854085
1996 Genomic organization of a mouse MHC class II region including the H2-M and Lmp2 loci. Immunogenetics 19 8575819
2015 Association between LMP2 and LMP7 gene polymorphisms and the risk of gastric cancer: A case-control study. Oncology letters 18 26171060
2006 In vitro anti-tumor immune response induced by dendritic cells transfected with EBV-LMP2 recombinant adenovirus. Biochemical and biophysical research communications 18 16842756
2022 Identification of PSMB9 and CXCL13 as Immune-related Diagnostic Markers for Rheumatoid Arthritis by Machine Learning. Current pharmaceutical design 17 36045515
1997 In vivo growth of Epstein-Barr virus transformed B cells with mutations in latent membrane protein 2 (LMP2). Archives of virology 17 9170499
2021 The Immunoproteasome Subunits LMP2, LMP7 and MECL-1 Are Crucial Along the Induction of Cerebral Toxoplasmosis. Frontiers in immunology 16 33968021
2021 Identification and characterization of a novel Epstein-Barr Virus-encoded circular RNA from LMP-2 Gene. Scientific reports 16 34257379
2020 LMP2-DC Vaccine Elicits Specific EBV-LMP2 Response to Effectively Improve Immunotherapy in Patients with Nasopharyngeal Cancer. Biomedical and environmental sciences : BES 16 33771238
2011 A bright approach to the immunoproteasome: development of LMP2/β1i-specific imaging probes. Bioorganic & medicinal chemistry 16 21741845
2000 The expression of MHC class I, TAP1/2, and LMP2/7 gene in human gastric cancer cell lines. International journal of oncology 15 10811990

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