Affinage

PSMB5

Proteasome subunit beta type-5 · UniProt P28074

Round 2 corrected
Length
263 aa
Mass
28.5 kDa
Annotated
2026-04-28
130 papers in source corpus 25 papers cited in narrative 25 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PSMB5 encodes the β5 catalytic subunit of the 20S proteasome, harboring a threonine-based active site that provides the principal chymotrypsin-like peptidase activity of the ubiquitin–proteasome system (PMID:8811196, PMID:9312091). Its expression is maintained basally by THAP1 and induced by Nrf2-ARE, STAT3, Gα12/13, TGF-β/Smad3, and BRD2, while miR-142-3p and miR-127-3p post-transcriptionally repress PSMB5 levels; IFN-γ triggers displacement of PSMB5 by the immunoproteasome paralog LMP7, remodeling cleavage specificity for MHC class I antigen presentation (PMID:39929834, PMID:24627483, PMID:16723119, PMID:9382924, PMID:32866906). Bortezomib binds directly within the PSMB5 active-site pocket at residues Ala49/Ala50, and point mutations at these positions or PSMB5 overexpression confer proteasome-inhibitor resistance by reducing drug binding and preventing ER stress–mediated apoptosis, while ISG20L2 independently competes with PSMB5 for bortezomib (PMID:18565852, PMID:19426847, PMID:20555361, PMID:36040812). Beyond bulk proteolysis, PSMB5-dependent degradation of specific substrates such as Drp1 suppresses mitochondrial fission, and altered PSMB5 activity modulates ROS-dependent NLRP3 inflammasome activation, Hobit-driven tissue-resident memory T cell differentiation, and Nmnat2/SIRT6/NF-κB signaling in cardiac hypertrophy (PMID:30762899, PMID:36061354, PMID:39037181, PMID:33315278).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1996 High

    Identification of PSMB5 as a catalytic subunit of the 20S proteasome with a threonine-based active site responsible for chymotrypsin-like activity resolved the longstanding question of which subunits harbor the proteolytic centers of the multicatalytic protease.

    Evidence Biochemical purification, kinetic analysis, and active-site characterization synthesized across multiple labs

    PMID:8811196

    Open questions at the time
    • Crystal structure of human PSMB5 in the 20S context was not yet available
    • Relative contribution of β5 versus β1/β2 to overall proteasomal flux was not quantified
  2. 1997 High

    Active-site-directed inhibitor labeling confirmed that PSMB5 is one of the catalytically active subunits and established that IFN-γ-induced LMP7 displaces PSMB5, fundamentally altering proteasome cleavage specificity for immune function.

    Evidence Radiolabeled peptidyl inhibitor labeling with 2D-PAGE/HPLC of purified 20S/26S proteasomes; genomic cloning showing distinct evolutionary origin of PSMB5 vs. LMP7

    PMID:9312091 PMID:9382924

    Open questions at the time
    • Mechanism governing selective incorporation of LMP7 versus PSMB5 into assembling proteasomes was unresolved
    • In vivo antigen repertoire consequences of β5↔LMP7 exchange not directly measured
  3. 2006 High

    Discovery that Nrf2-ARE elements in the PSMB5 promoter mediate stress-responsive transcriptional induction established the first defined pathway linking oxidative stress sensing to proteasome subunit upregulation.

    Evidence Promoter-reporter mutagenesis of AREs plus validation in nrf2-null cells

    PMID:16723119

    Open questions at the time
    • Whether Nrf2 coordinately induces all catalytic β subunits or selectively PSMB5 was unclear
    • Physiological stimuli beyond 3-methylcholanthrene activating this axis were not tested
  4. 2008 High

    Identification of the Ala49Thr mutation in the bortezomib-binding pocket of PSMB5 — combined with up to 60-fold PSMB5 overexpression — as the molecular basis of acquired bortezomib resistance resolved a critical question for proteasome inhibitor pharmacology.

    Evidence DNA sequencing, siRNA rescue of sensitivity, and chymotrypsin-like activity assay in THP1 and Jurkat resistant lines; FISH-confirmed gene amplification

    PMID:18562081 PMID:18565852

    Open questions at the time
    • Whether PSMB5 mutations occur in clinical bortezomib-refractory patients at appreciable frequency was unknown
    • Structural basis of how Ala49 mutations alter the binding pocket was modeled but not crystallographically resolved
  5. 2009 High

    Systematic mutagenesis at Ala49 and Ala50 established a quantitative structure–resistance relationship, demonstrating that both residues form the critical bortezomib-docking contacts and that double mutations confer >60-fold resistance.

    Evidence Multiple independent PSMB5 point mutations (Ala49Thr, Ala49Val, Ala49Thr+Ala50Val) with graded cytotoxicity and activity data in Jurkat clones

    PMID:19426847

    Open questions at the time
    • Cross-resistance profile to next-generation inhibitors had not yet been evaluated
    • Impact of these mutations on substrate specificity beyond drug binding was not assessed
  6. 2010 High

    The mechanistic link between PSMB5 mutations and drug resistance was completed by showing that mutant PSMB5 prevents bortezomib-induced accumulation of polyubiquitinated proteins and catastrophic ER stress/CHOP induction, while Gα12/13 signaling was identified as an upstream transcriptional regulator of PSMB5.

    Evidence Transfection of mutant vs. wild-type PSMB5 with ER stress readouts; bidirectional Gα12/13 manipulation with proteasome activity assays

    PMID:20478922 PMID:20555361

    Open questions at the time
    • Whether Gα12/13 acts through Nrf2, STAT3, or an independent transcription factor on the PSMB5 promoter was unresolved
    • In vivo relevance of Gα12/13-PSMB5 axis in tumor drug response was untested
  7. 2012 Medium

    PSMB5 mutations were shown to confer cross-resistance to carfilzomib and related next-generation proteasome inhibitors, indicating the binding pocket alterations are not bortezomib-specific; P-glycoprotein overexpression was identified as an independent co-resistance mechanism.

    Evidence Multi-inhibitor cytotoxicity and activity assays with Pgp inhibitor reversal in THP1 resistant sublines

    PMID:22235146

    Open questions at the time
    • Relative clinical prevalence of PSMB5 mutation versus Pgp-mediated resistance was unknown
    • Whether newer epoxyketone inhibitors fully bypass Ala49/50 mutations required structural studies
  8. 2014 High

    STAT3 was established as a direct transcriptional activator of PSMB5 via the EGF-EGFR axis, adding a growth-factor-driven regulatory input, while PSMB5 overexpression was shown to restore proteasome activity and proliferation in senescent stromal cells via Cyclin D1/CDK4.

    Evidence Bidirectional STAT3 manipulation with promoter-reporter assays; PSMB5 gain/loss-of-function in senescent bone marrow stromal cells with proliferation and survival readouts

    PMID:24393841 PMID:24627483

    Open questions at the time
    • Whether STAT3 and Nrf2 act on overlapping or distinct PSMB5 promoter elements was not determined
    • Cyclin D1 as a direct PSMB5-degraded substrate versus indirect effect was unclear
  9. 2017 Medium

    TGF-β/Smad3 was shown to directly bind the PSMB5 promoter via an SBE, adding a tissue-context-dependent transcriptional input, while PSMB5 knockdown in breast cancer cells inhibited growth, migration, and M2 macrophage polarization, broadening PSMB5's biological roles beyond proteolysis per se.

    Evidence EMSA for Smad3-SBE binding plus TGF-βRI inhibitor; shRNA in MDA-MB-231 with in vivo tumor model and THP-1 macrophage differentiation assays

    PMID:28807746 PMID:29218236

    Open questions at the time
    • Substrates whose degradation mediates the M1/M2 polarization shift were not identified
    • Tissue-specific integration of multiple transcription factors on the PSMB5 promoter lacked a unified model
  10. 2019 Medium

    Two miRNAs — miR-127-3p and miR-142-3p — were validated as direct post-transcriptional repressors of PSMB5 via 3ʹ-UTR targeting, establishing that PSMB5 levels are tuned by both transcriptional and post-transcriptional mechanisms; PSMB5-mediated degradation of Drp1 was identified as a specific substrate-level mechanism suppressing mitochondrial fission.

    Evidence 3ʹ-UTR luciferase reporters for both miRNAs; CTCF-miR-127-3p axis in prostate cancer; Nrf2 siRNA plus epoxomicin blockade confirming PSMB5→Drp1 degradation in endothelial cells

    PMID:30762899 PMID:31562641 PMID:32866906

    Open questions at the time
    • Whether Drp1 is directly ubiquitinated for PSMB5-mediated degradation or indirectly stabilized was unresolved
    • Quantitative impact of miRNA regulation on steady-state proteasome pools in vivo was not measured
  11. 2021 Medium

    PSMB5 was positioned upstream of an Nmnat2→SIRT6→NF-κB cardioprotective axis, and an HMGB1/CXCR4 pathway was shown to signal through PSMB5 to degrade Drp1 independently of Nrf2, expanding the upstream receptor inputs that converge on PSMB5-dependent proteostasis.

    Evidence PSMB5 knockdown attenuating EGCG anti-hypertrophic effects with NF-κB EMSA/reporter; receptor-specific inhibitors (AMD3100) and epoxomicin dissecting HMGB1→CXCR4→PSMB5→Drp1 axis

    PMID:33315278 PMID:34394840

    Open questions at the time
    • Direct physical interaction between CXCR4 signaling intermediates and PSMB5 promoter elements was not demonstrated
    • Whether PSMB5 directly stabilizes Nmnat2 or prevents its degradation was ambiguous
  12. 2022 High

    ISG20L2 was identified as a direct competitor of PSMB5 for bortezomib binding, revealing a novel resistance mechanism independent of PSMB5 mutation; simultaneously, PSMB5 overexpression was shown to suppress NLRP3 inflammasome activation via ROS reduction, and reduced PSMB5 expression was linked to CGG repeat-associated neurodegeneration in FXTAS models.

    Evidence Biotinylated bortezomib pull-down plus SPR for ISG20L2; PSMB5 overexpression with NLRP3/ROS readouts in DSS colitis model; cross-species PSMB5 knockdown in Drosophila FXTAS plus human eQTL association

    PMID:35617426 PMID:36040812 PMID:36061354

    Open questions at the time
    • Structural basis of ISG20L2-bortezomib interaction was not resolved
    • Whether PSMB5's ROS-modulating effect is direct or secondary to altered proteostasis was unclear
    • Mechanism by which reduced PSMB5 alleviates CGG repeat toxicity (RAN translation vs. RNA-mediated) was not fully disentangled
  13. 2024 Medium

    BRD2 was identified as a direct transcriptional activator of PSMB5 by ChIP-qPCR, and metabolic succinylation of BRD2 in rheumatoid arthritis T cells impairs PSMB5 transcription, leading to Hobit accumulation and tissue-resident memory T cell differentiation — linking proteasome dysfunction to autoimmune pathology.

    Evidence BRD2 ChIP-qPCR at PSMB5 promoter, succinyl-CoA manipulation, Hobit knockdown rescue, humanized NSG chimera model

    PMID:39037181

    Open questions at the time
    • Whether Hobit is a direct PSMB5 degradation substrate or accumulates indirectly was not established
    • Generalizability of succinylation-BRD2-PSMB5 axis beyond RA T cells was untested
  14. 2025 High

    Two independent studies established THAP1 as the critical basal transcriptional regulator of PSMB5, demonstrating that THAP1 loss reduces PSMB5 expression, disrupts proteasome assembly, impairs proteostasis, and causes cell death — rescued by exogenous PSMB5 — implicating proteasome dysfunction in DYT6 dystonia pathogenesis.

    Evidence Genome-wide CRISPR coessentiality screen, THAP1 knockout with PSMB5 rescue, proteasome assembly assays, deep mutational scan of THAP1 variants correlated with PSMB5 regulatory capacity

    PMID:39929834 PMID:39952963

    Open questions at the time
    • Direct THAP1 binding site(s) on the PSMB5 promoter were not mapped at base-pair resolution in these studies
    • Whether THAP1-PSMB5 dysregulation is the primary driver of DYT6 neurodegeneration versus other THAP1 targets requires further dissection

Open questions

Synthesis pass · forward-looking unresolved questions
  • A unified model integrating how multiple transcription factors (THAP1, Nrf2, STAT3, Smad3, BRD2, Gα12/13) and post-transcriptional regulators (miR-142-3p, miR-127-3p) are hierarchically organized on the PSMB5 promoter under different physiological and stress conditions remains to be established, along with systematic identification of PSMB5-specific degradation substrates beyond Drp1 and Hobit.
  • No integrated promoter occupancy map combining all known PSMB5 transcriptional regulators exists
  • Systematic substrate profiling (e.g., TAILS or ubiquitin-remnant proteomics) for PSMB5-specific cleavage has not been performed
  • Whether PSMB5 mutations in drug-resistant tumors occur at clinically meaningful frequencies remains unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016787 hydrolase activity 2 GO:0140096 catalytic activity, acting on a protein 2
Localization
GO:0005829 cytosol 2
Pathway
R-HSA-1643685 Disease 6 R-HSA-392499 Metabolism of proteins 5 R-HSA-168256 Immune System 3
Partners
BRD2DRP1ISG20L2LMP7STAT3THAP1
Complex memberships
20S proteasome26S proteasome

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 Radiolabeling of 20S and 26S proteasomes with active-site-directed peptidyl chloromethane and diazomethane inhibitors showed that the MB1 subunit (PSMB5) is one of the catalytic components associated with chymotrypsin-like and trypsin-like peptidase activities; incorporation of label into PSMB5 was blocked by prior treatment with calpain inhibitor or 3,4-dichloroisocoumarin, confirming active-site involvement. Radiolabeled active-site inhibitor labeling, 2D-PAGE, HPLC, immunoblotting with subunit-specific antibodies The Journal of Biological Chemistry High 9312091
1996 The 20S proteasome β5 subunit (PSMB5/MB1) harbors a threonine-based active site and contributes to the chymotrypsin-like peptidase activity of the multicatalytic protease complex; the 26S proteasome (formed by association of 20S with the 19S regulatory complex) degrades ubiquitinated proteins in an ATP-dependent manner. Biochemical purification, kinetic analysis, active-site characterization (review synthesizing multiple labs' reconstitution and inhibitor studies) Annual Review of Biochemistry High 8811196
1997 The mouse Psmb5 gene encoding the constitutively expressed β5 proteasome subunit is composed of three exons spanning ~5 kb, with a unique exon-intron organization radically different from its paralog Lmp7 (PSMB8), suggesting distinct evolutionary history; upon IFN-γ stimulation, PSMB5 is displaced from the 20S proteasome by LMP7, altering cleavage specificity to facilitate MHC class I antigen presentation. Genomic cloning, sequencing, interspecific backcross mapping, fluorescence in situ hybridization Immunogenetics Medium 9382924
2006 PSMB5 expression is transcriptionally induced by the bifunctional enzyme inducer 3-methylcholanthrene through the Nrf2-ARE pathway but not through the AhR/Arnt-XRE pathway; mutation of the proximal AREs in the Psmb5 promoter abolished inducibility, and 3-MC failed to induce PSMB5 in nrf2-null cells. Luciferase reporter assay with ARE/XRE deletion/mutation constructs, overexpression of AhR/Arnt, nrf2-null cell comparison, nuclear Nrf2 level measurement Biochemical and Biophysical Research Communications High 16723119
2008 Acquired bortezomib resistance in THP1 myelomonocytic cells is associated with (1) an Ala49Thr point mutation in the bortezomib-binding pocket of PSMB5 and (2) selective overexpression of PSMB5 protein up to 60-fold without comparable upregulation of other proteasome subunits; siRNA-mediated silencing of PSMB5 restored bortezomib sensitivity, confirming PSMB5 as the direct resistance determinant. DNA sequencing, Western blot, siRNA knockdown, cytotoxicity assays, chymotrypsin-like activity assay Blood High 18565852
2008 Overexpression and gene amplification of PSMB5 (demonstrated by FISH) in bortezomib-resistant Jurkat T-lymphoblastic leukemia cells increases chymotrypsin-like proteasome activity and correlates with upregulated NF-κB activity after bortezomib treatment, suggesting PSMB5 amplification-driven resistance operates through sustained NF-κB pathway. RT-qPCR, in situ hybridization/FISH, fluorometric chymotrypsin-like activity assay, Western blot for IκB-α and P-gp Experimental Hematology Medium 18562081
2009 Three distinct PSMB5 mutations (G322A→Ala49Thr, C323T→Ala49Val, and compound G322A+C326T→Ala49Thr+Ala50Val) confer graded levels of bortezomib resistance (22-, 39-, and 67-fold, respectively) in Jurkat cells; resistance correlates with reduced inhibition of chymotrypsin-like activity by bortezomib, establishing that amino acids 49 and 50 of PSMB5 are critical for bortezomib binding. cDNA sequencing, limited dilution cloning, cytotoxicity assays, fluorometric chymotrypsin-like activity assay Experimental Hematology High 19426847
2010 A G322A point mutation in PSMB5 in bortezomib-resistant myeloma cell lines causes conformational changes in the bortezomib-binding pocket, reducing accumulation of polyubiquitinated proteins and preventing catastrophic ER stress/CHOP induction; transfection of mutant PSMB5 into parental cells recapitulated reduced bortezomib-induced apoptosis, directly linking the PSMB5 mutation to ER stress avoidance. DNA sequencing, transfection of wild-type vs. mutant PSMB5, Western blot for polyubiquitinated proteins and CHOP, caspase/BH3-only protein analysis Leukemia High 20555361
2010 Inhibition of Gα12/13 signaling downregulates PSMB5 expression at the mRNA and protein levels, enhances bortezomib-mediated cytotoxicity, and reduces chymotrypsin-like proteasome activity; active Gα12QL or Gα13QL reversed these effects, placing Gα12/13 upstream of PSMB5 regulation. RT-PCR, Western blot, proteasome activity assay, transfection with active mutants and minigene constructs, cytotoxicity assay Carcinogenesis Medium 20478922
2012 PSMB5 mutations (identified in bortezomib-resistant THP1 sublines) confer marked cross-resistance to second-generation proteasome inhibitors carfilzomib, ONX0912, and ONX0914, though less pronounced than to bortezomib; P-glycoprotein overexpression provides an independent resistance mechanism by reducing effective intracellular drug concentration, and Pgp inhibition with reversin 121 restores parental sensitivity. Cytotoxicity assays, β5 subunit chymotrypsin-like activity assay, flow cytometry for Pgp, Pgp inhibitor reversal experiments The Journal of Pharmacology and Experimental Therapeutics Medium 22235146
2014 STAT3 transcriptionally activates PSMB5 expression; knockdown of STAT3 decreases PSMB5 mRNA and protein, inhibition of phospho-STAT3 reduces PSMB5 in constitutively active-STAT3 cells, and accumulation of active STAT3 induces PSMB5 promoter activity. EGF-induced upregulation of β subunits including PSMB5 was blocked by EGFR or STAT3 inhibition but not by PI3K/AKT or MEK/ERK inhibition. STAT3 knockdown, constitutively active STAT3 overexpression, luciferase promoter assay, Western blot, RT-PCR, pathway inhibitor panel The Journal of Biological Chemistry High 24627483
2014 Overexpression of PSMB5 in late-stage senescent human bone marrow stromal cells restores 20S proteasome activity and promotes cell growth potentially via upregulating the Cyclin D1/CDK4 complex; conversely, PSMB5 knockdown in early-stage cells reduces proteasome activity and proliferation, mimicking a senescent phenotype. PSMB5 overexpression also enhances cell survival under oxidative stress and preserves pluripotency. PSMB5 overexpression and siRNA knockdown, proteasome activity assay, BrdU/proliferation assay, Western blot for Cyclin D1/CDK4, H2O2 survival assay, neural differentiation assay Biochemical and Biophysical Research Communications High 24393841
2017 High expression of PSMB5 promotes M2 macrophage polarization and suppresses M1 differentiation; PSMB5 knockdown in THP-1 monocytes shifts differentiation toward M1 macrophages. PSMB5 knockdown in MDA-MB-231 breast cancer cells inhibits cell growth and migration. In vivo lentiviral PSMB5 shRNA delivery significantly reduced tumor growth in a subcutaneous mouse model. shRNA knockdown, colony formation assay, Boyden chamber migration assay, monocyte differentiation assay, in vivo subcutaneous tumor model American Journal of Cancer Research Medium 29218236
2017 20-HETE regulates PSMB5 expression in a tissue-specific manner through the TGF-β/Smad3 signaling pathway; Smad3 directly binds the Smad binding element (SBE) in the Psmb5 promoter as demonstrated by EMSA, and the TGF-β receptor I kinase inhibitor SB431542 reverses 20-HETE-induced changes in PSMB5 levels. Luciferase reporter assay, EMSA, TGF-β pathway inhibitor (SB431542), Western blot for TGF-β1, Smad3 phosphorylation, and PSMB5 Prostaglandins & Other Lipid Mediators Medium 28807746
2019 PSMB5 is a direct target of miR-127-3p; overexpression of miR-127-3p reduces PSMB5 protein and inhibits prostate cancer cell invasion and migration. CTCF transcription factor suppresses miR-127-3p expression by binding the miR-127-3p promoter, thereby indirectly upregulating PSMB5 to promote bone metastasis. Luciferase 3'UTR reporter assay, miR-127-3p overexpression, CTCF ChIP or promoter binding assay, invasion/migration assay FEBS Letters Medium 31562641
2019 Ilexgenin A (IA) increases PSMB5 expression in an Nrf2-dependent manner in endothelial cells; Nrf2 knockdown abolishes IA-induced PSMB5 upregulation. Increased PSMB5 activity promotes proteasomal degradation of Drp1, thereby suppressing mitochondrial fission and improving endothelial function. Proteasome inhibitor epoxomicin blocked IA's effect on Drp1 expression, confirming the PSMB5-mediated degradation mechanism. Nrf2 siRNA knockdown, Western blot for PSMB5 and Drp1, proteasome inhibitor (epoxomicin) treatment, mitochondrial morphology assessment Drug Development Research Medium 30762899
2020 Curcumin elevates miR-142-3p expression by inhibiting histone acetyltransferase p300, and miR-142-3p directly targets the PSMB5 3'UTR to reduce PSMB5 protein levels and chymotrypsin-like activity of the 20S proteasome; loss of p300 and PSMB5 each independently reduced cell proliferation in triple-negative breast cancer cells. miR-142-3p mimic/inhibitor, PSMB5 3'UTR luciferase reporter, p300 overexpression, fluorometric proteasome activity assay, BrdU proliferation assay, in vivo xenograft Phytomedicine High 32866906
2021 EGCG activates PSMB5 (20S proteasome β5, chymotrypsin-like activity) and may directly interact with PSMB5; activated PSMB5 is required for EGCG-induced upregulation of Nmnat2 protein expression. Nmnat2 subsequently activates SIRT6 histone deacetylase, which blocks NF-κB DNA binding activity induced by angiotensin II, thereby inhibiting cardiac hypertrophy. PSMB5 knockdown attenuated EGCG's anti-hypertrophic effects. RNA interference (PSMB5 knockdown), luciferase reporter for NF-κB, EMSA for NF-κB DNA binding, fluorometric SIRT6 activity assay, Western blot, in vivo aortic constriction model Acta Physiologica Medium 33315278
2021 rHMGB1 promotes mitochondrial fusion in endothelial cells via the CXCR4/PSMB5 pathway: rHMGB1 increases PSMB5 expression through CXCR4 (not TLR4, RAGE, or TLR2), and PSMB5 mediates proteasomal degradation of Drp1, reducing mitochondrial fission. Inhibition of PSMB5 with epoxomicin abolished rHMGB1-induced Drp1 downregulation and mitochondrial fusion, independent of NRF2. Specific receptor inhibitors (AMD3100/CXCR4, C29/TLR2, TAK-242/TLR4, FPS-ZM1/RAGE), epoxomicin (PSMB5 inhibitor), NRF2 siRNA, confocal/TEM mitochondrial morphology, Western blot Oxidative Medicine and Cellular Longevity Medium 34394840
2022 PSMB5 knockdown suppresses CGG repeat-associated neurodegeneration in both Drosophila FXTAS models and N2A cells; the PSMB5 expression QTL variant rs11543947-A is associated with decreased PSMB5 expression and delayed FXTAS onset in human FMR1 premutation carriers. PSMB5 knockdown reduces toxicity via both RAN translation and RNA-mediated mechanisms. Drosophila genetic screen (whole-genome sequencing + candidate knockdown), N2A cell knockdown, human genetic association (QTL analysis), RAN translation and RNA toxicity assays Proceedings of the National Academy of Sciences High 35617426
2022 ISG20L2 competes directly with PSMB5 for bortezomib binding: biotinylated bortezomib pull-down showed ISG20L2 competes with PSMB5 for drug binding, and surface plasmon resonance confirmed direct bortezomib-ISG20L2 interaction. In ISG20L2-high myeloma cells, ISG20L2 attenuates bortezomib binding to PSMB5, reducing proteasome inhibition and cell death. Biotinylated bortezomib pull-down assay, surface plasmon resonance, gain/loss-of-function in vitro and in vivo experiments, proteasome activity assay JCI Insight High 36040812
2022 PSMB5 overexpression in intestinal epithelial cells reduces LPS-induced NLRP3 inflammasome activation and pyroptosis by decreasing intracellular ROS generation; ROS scavenger NAC mimicked this protective effect, placing PSMB5 upstream of ROS-dependent NLRP3 activation in a model of ulcerative colitis. PSMB5 overexpression, NLRP3/caspase-1/ASC Western blot, LDH release assay, ROS measurement, NAC/Z-VAD-FMK/MCC950 pharmacological dissection, in vivo DSS colitis model Disease Markers Medium 36061354
2024 In rheumatoid arthritis T cells, elevated mitochondrial succinyl-CoA causes succinylation of BRD2 transcription factor, which impairs BRD2-dependent transcription of PSMB5; reduced PSMB5 leads to accumulation of the transcription factor Hobit, promoting CD4+ T cell differentiation into tissue-resident memory (Trm) cells and synovial inflammation. ChIP-qPCR validated direct BRD2 binding to the PSMB5 promoter. BRD2 chromatin immunoprecipitation-qPCR, Hobit knockdown, succinyl-CoA manipulation, humanized NSG chimera model, Trm differentiation assay Arthritis & Rheumatology Medium 39037181
2025 The transcription factor THAP1 (DYT6 dystonia gene) directly regulates PSMB5 gene expression to maintain basal proteasome activity; loss of THAP1 reduces PSMB5 levels, disrupts proteasome assembly, impairs proteostasis, and causes cell death. Exogenous PSMB5 expression rescues THAP1-deficient cell toxicity. A deep mutational scan of THAP1 variants correlated with PSMB5 regulatory capacity. Genome-wide CRISPR genetic screen (DepMap coessentiality), THAP1 knockout, PSMB5 exogenous rescue, proteasome assembly assay, ubiquitinated protein accumulation, RNA-seq, deep mutational scan Nature Communications High 39929834 39952963
2025 Complementary study confirms THAP1 transcriptionally activates PSMB5; THAP1 depletion decreases PSMB5 mRNA and protein, disrupts proteasome assembly, and increases ubiquitinated protein accumulation. These findings identify THAP1 as a critical regulator of proteasome function and suggest proteasome dysfunction contributes to DYT6 dystonia pathogenesis. THAP1 knockout/knockdown, Western blot, proteasome activity assay, ubiquitinated protein accumulation, RNA-seq transcriptional target definition Nature Communications High 39929834 39952963

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1996 Structure and functions of the 20S and 26S proteasomes. Annual review of biochemistry 2108 8811196
2002 Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein. Nature 1924 12167863
2012 Insights into RNA biology from an atlas of mammalian mRNA-binding proteins. Cell 1718 22658674
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2009 Recognition and processing of ubiquitin-protein conjugates by the proteasome. Annual review of biochemistry 1398 19489727
2011 Systematic and quantitative assessment of the ubiquitin-modified proteome. Molecular cell 1334 21906983
2009 Defining the human deubiquitinating enzyme interaction landscape. Cell 1282 19615732
2003 Broad antiretroviral defence by human APOBEC3G through lethal editing of nascent reverse transcripts. Nature 1236 12808466
2003 DNA deamination mediates innate immunity to retroviral infection. Cell 1150 12809610
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2003 Induction of APOBEC3G ubiquitination and degradation by an HIV-1 Vif-Cul5-SCF complex. Science (New York, N.Y.) 1006 14564014
2003 The cytidine deaminase CEM15 induces hypermutation in newly synthesized HIV-1 DNA. Nature 912 12808465
2013 Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization. Nature 870 23503661
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2009 A genome-wide RNAi screen identifies multiple synthetic lethal interactions with the Ras oncogene. Cell 843 19490893
2004 A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway. Nature cell biology 841 14743216
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
2003 The antiretroviral enzyme APOBEC3G is degraded by the proteasome in response to HIV-1 Vif. Nature medicine 798 14528300
2003 Species-specific exclusion of APOBEC3G from HIV-1 virions by Vif. Cell 763 12859895
2011 A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles. Molecular & cellular proteomics : MCP 749 21890473
2007 Large-scale mapping of human protein-protein interactions by mass spectrometry. Molecular systems biology 733 17353931
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2012 A census of human soluble protein complexes. Cell 689 22939629
2003 HIV-1 Vif protein binds the editing enzyme APOBEC3G and induces its degradation. Nature medicine 679 14528301
2015 Gene essentiality and synthetic lethality in haploid human cells. Science (New York, N.Y.) 657 26472760
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2008 Large-scale proteomics and phosphoproteomics of urinary exosomes. Journal of the American Society of Nephrology : JASN 607 19056867
2003 HIV-1 Vif blocks the antiviral activity of APOBEC3G by impairing both its translation and intracellular stability. Molecular cell 607 14527406
2006 Testing gene function early in the B cell lineage in mb1-cre mice. Proceedings of the National Academy of Sciences of the United States of America 497 16940357
2008 Molecular basis of bortezomib resistance: proteasome subunit beta5 (PSMB5) gene mutation and overexpression of PSMB5 protein. Blood 383 18565852
1988 B lymphocyte lineage-restricted expression of mb-1, a gene with CD3-like structural properties. The EMBO journal 295 2463161
2010 Bortezomib-resistant myeloma cell lines: a role for mutated PSMB5 in preventing the accumulation of unfolded proteins and fatal ER stress. Leukemia 150 20555361
2004 Early B cell factor cooperates with Runx1 and mediates epigenetic changes associated with mb-1 transcription. Nature immunology 149 15361869
1992 An inhibitory carboxyl-terminal domain in Ets-1 and Ets-2 mediates differential binding of ETS family factors to promoter sequences of the mb-1 gene. Proceedings of the National Academy of Sciences of the United States of America 146 1409581
1991 IgM antigen receptor complex contains phosphoprotein products of B29 and mb-1 genes. Proceedings of the National Academy of Sciences of the United States of America 135 2023945
1991 The IgM-associated protein mb-1 as a marker of normal and neoplastic B cells. Journal of immunology (Baltimore, Md. : 1950) 130 1747162
1991 A novel lineage-specific nuclear factor regulates mb-1 gene transcription at the early stages of B cell differentiation. The EMBO journal 125 1915300
2003 Somatic hypermutation of the B cell receptor genes B29 (Igbeta, CD79b) and mb1 (Igalpha, CD79a). Proceedings of the National Academy of Sciences of the United States of America 106 12651942
2012 Inactivating PSMB5 mutations and P-glycoprotein (multidrug resistance-associated protein/ATP-binding cassette B1) mediate resistance to proteasome inhibitors: ex vivo efficacy of (immuno)proteasome inhibitors in mononuclear blood cells from patients with rheumatoid arthritis. The Journal of pharmacology and experimental therapeutics 85 22235146
1991 Heterogeneously initiated transcription from the pre-B- and B-cell-specific mb-1 promoter: analysis of the requirement for upstream factor-binding sites and initiation site sequences. Molecular and cellular biology 85 1922076
2002 Early B-cell factor, E2A, and Pax-5 cooperate to activate the early B cell-specific mb-1 promoter. Molecular and cellular biology 82 12446773
2003 Activation of the early B-cell-specific mb-1 (Ig-alpha) gene by Pax-5 is dependent on an unmethylated Ets binding site. Molecular and cellular biology 76 12612069
2000 Gene cloning and nucleotide sequencing and properties of a cocaine esterase from Rhodococcus sp. strain MB1. Applied and environmental microbiology 76 10698749
1991 The membrane IgM-associated heterodimer on human B cells is a newly defined B cell antigen that contains the protein product of the mb-1 gene. Journal of immunology (Baltimore, Md. : 1950) 72 2033258
1990 Structure of the murine mb-1 gene encoding a putative sIgM-associated molecule. Journal of immunology (Baltimore, Md. : 1950) 69 2358676
1992 The membrane IgM-associated proteins MB-1 and Ig-beta are sufficient to promote surface expression of a partially functional B-cell antigen receptor in a nonlymphoid cell line. Proceedings of the National Academy of Sciences of the United States of America 68 1373499
2008 Overexpression of the PSMB5 gene contributes to bortezomib resistance in T-lymphoblastic lymphoma/leukemia cells derived from Jurkat line. Experimental hematology 67 18562081
1992 The B29 and mb-1 polypeptides are differentially expressed during human B cell differentiation. European journal of immunology 66 1396979
2014 Regulation of PSMB5 protein and β subunits of mammalian proteasome by constitutively activated signal transducer and activator of transcription 3 (STAT3): potential role in bortezomib-mediated anticancer therapy. The Journal of biological chemistry 64 24627483
2009 Different mutants of PSMB5 confer varying bortezomib resistance in T lymphoblastic lymphoma/leukemia cells derived from the Jurkat cell line. Experimental hematology 62 19426847
1992 BLyF, a novel cell-type- and stage-specific regulator of the B-lymphocyte gene mb-1. Molecular and cellular biology 61 1545794
1994 The expression of the B-cell marker mb-1 (CD79a) in Hodgkin's disease. Histopathology 56 7520411
1993 mb-1: a new marker for B-lineage lymphoblastic leukemia. Blood 56 8338949
2017 PSMB5 plays a dual role in cancer development and immunosuppression. American journal of cancer research 55 29218236
1997 Catalytic properties of 26 S and 20 S proteasomes and radiolabeling of MB1, LMP7, and C7 subunits associated with trypsin-like and chymotrypsin-like activities. The Journal of biological chemistry 55 9312091
1991 Signal transmission through the B cell-specific MB-1 molecule at the pre-B cell stage. International immunology 52 1709046
1987 GABAergic input to the synaptic terminals of mb1 bipolar cells in the goldfish retina. Brain research 51 3300849
1999 Structure analysis of a class II transposon encoding the mercury resistance of the Gram-positive Bacterium bacillus megaterium MB1, a strain isolated from minamata bay, Japan. Gene 50 10395910
1992 Human mb-1 gene: complete cDNA sequence and its expression in B cells bearing membrane Ig of various isotypes. Journal of immunology (Baltimore, Md. : 1950) 49 1729378
2006 Induction of 26S proteasome subunit PSMB5 by the bifunctional inducer 3-methylcholanthrene through the Nrf2-ARE, but not the AhR/Arnt-XRE, pathway. Biochemical and biophysical research communications 48 16723119
2015 Production, extraction and stabilization of lutein from microalga Chlorella sorokiniana MB-1. Bioresource technology 43 26519703
1986 MB1, a quail leukocyte-endothelium antigen: partial characterization of the cell surface and secreted forms in cultured endothelial cells. Proceedings of the National Academy of Sciences of the United States of America 41 3466174
2020 Curcumin inhibits proteasome activity in triple-negative breast cancer cells through regulating p300/miR-142-3p/PSMB5 axis. Phytomedicine : international journal of phytotherapy and phytopharmacology 40 32866906
1992 Molecular cloning and expression pattern of a human gene homologous to the murine mb-1 gene. Journal of immunology (Baltimore, Md. : 1950) 40 1538135
1999 Identification of three merB genes and characterization of a broad-spectrum mercury resistance module encoded by a class II transposon of Bacillus megaterium strain MB1. Gene 38 10548738
1993 Cross-linking of B cell receptor-related MB-1 molecule induces protein tyrosine phosphorylation in early B lineage cells. Journal of immunology (Baltimore, Md. : 1950) 37 8473731
2006 Expression of mercuric reductase from Bacillus megaterium MB1 in eukaryotic microalga Chlorella sp. DT: an approach for mercury phytoremediation. Applied microbiology and biotechnology 36 16547702
1991 Direct identification of the putative surface IgM receptor-associated molecule encoded by murine B cell-specific mb-1 gene. Journal of immunology (Baltimore, Md. : 1950) 36 1993847
2021 EGCG inhibits pressure overload-induced cardiac hypertrophy via the PSMB5/Nmnat2/SIRT6-dependent signalling pathways. Acta physiologica (Oxford, England) 34 33315278
1993 Expression of the Ig-associated heterodimer (mb-1 and B29) in Hodgkin's disease. Histopathology 33 8454258
2019 Ilexgenin A inhibits mitochondrial fission and promote Drp1 degradation by Nrf2-induced PSMB5 in endothelial cells. Drug development research 32 30762899
2013 Complete genome sequence of the hydrogenotrophic Archaeon Methanobacterium sp. Mb1 isolated from a production-scale biogas plant. Journal of biotechnology 32 24184088
1983 Primary structure of human class II histocompatibility antigens 3rd communication. Amino acid sequence comparison between DR and DC subclass antigens derived from a lymphoblastoid B cell line homozygous at the HLA loci (HLA-A3,3; B7,7; Dw2,2; DR2,2: MT1,1; Dc1,1: MB1,1). Hoppe-Seyler's Zeitschrift fur physiologische Chemie 32 6576979
2018 PSMB5 is associated with proliferation and drug resistance in triple-negative breast cancer. The International journal of biological markers 30 28623645
1994 Identification of a 52-kDa molecule (p52) coprecipitated with the Ig receptor-related MB-1 protein that is inducibly phosphorylated by the stimulation with phorbol myristate acetate. Journal of immunology (Baltimore, Md. : 1950) 30 8144881
1987 Immunohistochemical staining of non-Hodgkin's lymphoma in paraffin sections using the MB1 and MT1 monoclonal antibodies. The Journal of pathology 29 3323430
2019 Transcriptional downregulation of miR-127-3p by CTCF promotes prostate cancer bone metastasis by targeting PSMB5. FEBS letters 28 31562641
1996 VLA-beta 1 integrin subunit-specific monoclonal antibodies MB1.1 and MB1.2: binding to epitopes not dependent on thymocyte development or regulated by phorbol ester and divalent cations. Hybridoma 26 8743292
1995 Design, expression, and initial characterization of MB1, a de novo protein enriched in essential amino acids. Bio/technology (Nature Publishing Company) 26 9636274
1993 Surface transport and internalization of the membrane IgM H chain in the absence of the Mb-1 and B29 proteins. Journal of immunology (Baltimore, Md. : 1950) 24 8326121
1983 Dissociation in expression of MB1/MT1 and DR1 alloantigens in mutants of a lymphoblastoid cell line. Journal of immunology (Baltimore, Md. : 1950) 24 6411812
1995 The novel variants of mb-1 and B29 transcripts generated by alternative mRNA splicing. Immunology letters 23 8747711
1994 Structure, chromosomal localization, and methylation pattern of the human mb-1 gene. Journal of immunology (Baltimore, Md. : 1950) 23 8207205
2014 Ameliorating replicative senescence of human bone marrow stromal cells by PSMB5 overexpression. Biochemical and biophysical research communications 22 24393841
1994 Isolation and chemical characterization of the human B29 and mb-1 proteins of the B cell antigen receptor complex. Molecular immunology 22 7514267
2010 G(alpha)12/13 inhibition enhances the anticancer effect of bortezomib through PSMB5 downregulation. Carcinogenesis 21 20478922
2009 Down-regulation of proteasomal subunit MB1 is an independent predictor of improved survival in ovarian cancer. Gynecologic oncology 21 19243813
1996 Differential expression of B29 (CD79b) and mb-1 (CD79a) proteins in acute lymphoblastic leukaemia. Leukemia 21 8656670
2005 Estrogen receptor-alpha splice variants in the medial mamillary nucleus of Alzheimer's disease patients: identification of a novel MB1 isoform. The Journal of clinical endocrinology and metabolism 20 15755860
2002 Bob1 (OCA-B/OBF-1) differential transactivation of the B cell-specific B29 (Ig beta) and mb-1 (Ig alpha) promoters. Journal of immunology (Baltimore, Md. : 1950) 18 11907094
1992 Structure and expression of the mb-1 transcript in human lymphoid cells. Clinical and experimental immunology 17 1395095
1984 Role of HLA class II products in proliferative T-lymphocyte responses to PPD. Evidence of a regulatory influence associated with MB1. Scandinavian journal of immunology 16 6083600
2020 The role of PSMB5 in sodium arsenite-induced oxidative stress in L-02 cells. Cell stress & chaperones 15 32301004
1997 Intratumoral microdistribution of [131I]MB-1 in patients with B-cell lymphoma following radioimmunotherapy. Nuclear medicine and biology 15 9352537
2007 Age-dependent ERalpha MB1 splice variant expression in discrete areas of the human brain. Neurobiology of aging 14 17368651
1997 Effects of basic fibroblast growth factor on the differentiation, growth, and viability of a new human medulloblastoma cell line (UM-MB1). The American journal of pathology 14 9284836
1984 [Primary structure of human class II histocompatibility antigens (HLA-D). I. Isolation, purification and characterization of the HLA-D alpha/beta chain complex from a homozygous lymphoblastoid B cell line, H2LCL (HLA-A3,3;B7,7;Dw2, 2;DR2,2;MT1,1;DC1,1;MB1,1]. Hoppe-Seyler's Zeitschrift fur physiologische Chemie 14 6334638
2022 Identification of PSMB5 as a genetic modifier of fragile X-associated tremor/ataxia syndrome. Proceedings of the National Academy of Sciences of the United States of America 13 35617426
2017 20-HETE regulated PSMB5 expression via TGF-β/Smad signaling pathway. Prostaglandins & other lipid mediators 13 28807746
2006 Biotransformation of citrinin to decarboxycitrinin using an organic solvent-tolerant marine bacterium, Moraxella sp. MB1. Marine biotechnology (New York, N.Y.) 13 16467989
1994 Tyrosine phosphorylation of MB-1, B29, and HS1 proteins in human B cells following receptor crosslinking. Immunology letters 13 7927516
2013 Leuconostoc citreum MB1 as biocontrol agent of Listeria monocytogenes in milk. The Journal of dairy research 12 24351750
2000 An essential octamer motif in the mb-1 (Igalpha) promoter. Molecular immunology 12 11000405
1997 Structural analysis and chromosomal localization of the mouse Psmb5 gene coding for the constitutively expressed beta-type proteasome subunit. Immunogenetics 12 9382924
1996 Divergent intron arrangement in the MB1/LMP7 proteasome gene pair. Immunogenetics 11 8753855
1994 Ig heavy chain extracellular spacer confers unique glycosylation of the Mb-1 component of the B cell antigen receptor complex. Journal of immunology (Baltimore, Md. : 1950) 11 8144961
1993 Induction of tyrosine phosphorylation in human B lineage cells by crosslinking MB-1 molecule of B cell receptor-related heterodimer complex. Biochemical and biophysical research communications 11 7506545
1987 MB1, a quail leukocyte/vascular endothelium antigen: characterization of the lymphocyte-surface form and identification of its secreted counterpart as alpha 2-macroglobulin. Cell differentiation 11 2443255
1999 Characterization of MB-1. A dimeric helical protein with a compact core. European journal of biochemistry 10 10336631
1996 How to differentiate between T-cell-rich B-cell lymphoma and lymphocyte-predominant Hodgkin's disease. Evidence for the value of MB1 and 4KB5 immunostaining. The Journal of pathology 10 8758204
2002 Sequencing of amphioxus PSMB5/8 gene and phylogenetic position of agnathan sequences. Gene 9 11814690
1997 Prediction of folding stability and degradability of the de novo designed protein MB-1 in cow rumen. Applied biochemistry and biotechnology 9 9204520
1988 Immunohistochemical characterization of osteoclasts and osteoclast-like cells with monoclonal antibody MB1 on paraffin-embedded tissues. The Journal of pathology 9 2904980
1985 Mb1, a plasma membrane antigen selectively expressed by U-937 cells. Blood 9 3890983
2022 ISG20L2 suppresses bortezomib antimyeloma activity by attenuating bortezomib binding to PSMB5. JCI insight 8 36040812
2022 PSMB5 Alleviates Ulcerative Colitis by Inhibiting ROS-Dependent NLRP3 Inflammasome-Mediated Pyroptosis. Disease markers 8 36061354
2005 Natural selection during functional divergence to LMP7 and proteasome subunit X (PSMB5) following gene duplication. Journal of molecular evolution 8 15785850
1994 Down-regulation of membrane immunoglobulin-associated proteins, MB-1, B29 and Lyn, in AIDS-lymphomas and related conditions. Virchows Archiv : an international journal of pathology 8 8032536
2025 The DYT6 dystonia causative protein THAP1 is responsible for proteasome activity via PSMB5 transcriptional regulation. Nature communications 7 39952963
2024 Mitochondrial Control of Proteasomal Psmb5 Drives the Differentiation of Tissue-Resident Memory T Cells in Patients with Rheumatoid Arthritis. Arthritis & rheumatology (Hoboken, N.J.) 7 39037181
2021 Mitochondrial uncoupler MB1-47 is efficacious in treating hepatic metastasis of pancreatic cancer in murine tumor transplantation models. Oncogene 7 33649533
2021 Recombinant High-Mobility Group Box 1 (rHMGB1) Promotes NRF2-Independent Mitochondrial Fusion through CXCR4/PSMB5-Mediated Drp1 Degradation in Endothelial Cells. Oxidative medicine and cellular longevity 7 34394840
2000 Development of an optimized feeding technology for dairy cows: improvement in resistance to ruminal proteases in the de novo-designed protein MB-1. Applied biochemistry and biotechnology 7 10982233
1996 Regulatory elements of the mb-1 gene encoding the Ig-alpha component of the human B-cell antigen receptor. Molecular immunology 7 9171887
2025 Loss-of-function mutations in the dystonia gene THAP1 impair proteasome function by inhibiting PSMB5 expression. Nature communications 6 39929834
2023 Dihydrocelastrol induces antitumor activity and enhances the sensitivity of bortezomib in resistant multiple myeloma by inhibiting STAT3-dependent PSMB5 regulation. Acta biochimica et biophysica Sinica 6 38009004
2020 Participation of a MADS-box transcription factor, Mb1, in regulation of the biocontrol potential in an insect fungal pathogen. Journal of invertebrate pathology 6 32007504
1992 Distribution of antigens detected with MB1, MB2 and MB3 on non-hematopoietic human organs and various tumors. Acta pathologica japonica 6 1636436