Affinage

PSMB2

Proteasome subunit beta type-2 · UniProt P49721

Length
201 aa
Mass
22.8 kDa
Annotated
2026-06-10
40 papers in source corpus 11 papers cited in narrative 11 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/6 claims corpus-supported (83%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PSMB2 encodes a structural beta subunit of the 20S proteasome proteolytic core, originally identified as one of 17 subunits of the mouse 20S proteasome and verified at the protein level (PMID:10436176). Its cellular dosage directly sets proteasome activity: knockdown suppresses proteasome activity, proliferation, and invasion while promoting apoptosis, and overexpression elevates proteasome activity and proliferation in a manner reversed by the proteasome inhibitor MG132, with loss-of-function additionally blocking NRF1 activation (PMID:36110152). These effects extend across multiple cancer contexts including hepatocellular carcinoma, gastric cancer, and glioma, where PSMB2 acts as a functional driver of growth and invasiveness (PMID:29780166, PMID:36110152, PMID:38467767). PSMB2 expression is post-transcriptionally controlled through NUDT21-dependent alternative polyadenylation, where loss of NUDT21 shifts to a proximal polyadenylation site, shortens the 3' UTR, and elevates PSMB2 (PMID:29780166). Beyond bulk degradation, PSMB2 serves as a direct engagement partner in VCP/p97-directed, SUMOylation-dependent and ubiquitin-independent proteolysis of a SUMO1-modified substrate (PMID:41288382). PSMB2 function is a selective dependency in ARID1A-deficient cells, and its suppression sensitizes cells to proteasome inhibition (PMID:21289309, PMID:37028423).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1997 Medium

    Establishing the genomic location of PSMB2 distinguished it from other beta-subunit genes and framed the question of how core subunit expression is independently coordinated.

    Evidence FISH mapping to human chromosome 1p34.2

    PMID:9344661

    Open questions at the time
    • Does not address protein function or assembly
    • No link between chromosomal location and regulation tested directly
  2. 1999 Medium

    Defining PSMB2 as a bona fide subunit of the 20S core answered whether it is a structural component of the proteasome rather than an accessory factor.

    Evidence cDNA cloning, 2D NEPHGE-PAGE, and antisera verification of mouse 20S proteasome subunits

    PMID:10436176

    Open questions at the time
    • No catalytic role assigned to PSMB2 itself
    • Assembly order and partner subunits within the core not resolved
  3. 2009 Low

    A transformation screen raised the possibility that PSMB2 dosage contributes to oncogenesis, prompting later functional cancer studies.

    Evidence Retroviral expression library focus formation assay in 3T3 fibroblasts

    PMID:19787249

    Open questions at the time
    • No mechanistic follow-up on how PSMB2 drives transformation
    • Single assay, no validation in tumor models
  4. 2011 Medium

    An RNAi screen showed that lowering PSMB2 sensitizes cells to proteasome inhibition, linking subunit dosage to drug response.

    Evidence Genome-wide siRNA screen in multiple myeloma cells with bortezomib co-treatment

    PMID:21289309

    Open questions at the time
    • Synergy mechanism not dissected
    • Does not distinguish PSMB2-specific from general core-subunit depletion effects
  5. 2018 Medium

    Identifying NUDT21-dependent alternative polyadenylation as a regulator of PSMB2 answered how its expression is post-transcriptionally tuned and connected this to tumor cell behavior.

    Evidence Global APA profiling with NUDT21 and PSMB2 knockdown plus proliferation/invasion assays in HCC cells

    PMID:29780166

    Open questions at the time
    • Mechanism by which elevated PSMB2 promotes proliferation not resolved
    • Does not establish whether 3' UTR shortening alters protein stability versus translation
  6. 2022 Medium

    Bidirectional perturbation established that PSMB2 dosage directly governs proteasome activity and downstream NRF1 activation, defining its causal role in cancer cell survival.

    Evidence siRNA knockdown and overexpression in gastric cancer cells with proteasome activity, EdU, TUNEL, MG132 rescue, and xenograft assays

    PMID:36110152

    Open questions at the time
    • Mechanism linking PSMB2 to NRF1 activation not detailed
    • Whether effects are core-assembly-dependent versus subunit-specific unresolved
  7. 2023 Medium

    A CRISPRi screen identified PSMB2 as a selective dependency in ARID1A-deficient cells, defining a synthetic lethal relationship exploitable by proteasome inhibition.

    Evidence Whole-genome CRISPRi screen in iPSCs replicated by pharmacological proteasome inhibition

    PMID:37028423

    Open questions at the time
    • Molecular basis of the ARID1A-PSMB2 dependency not defined
    • Whether dependency is PSMB2-specific or generic to proteasome function unclear
  8. 2024 Medium

    Stable knockdown in glioma confirmed PSMB2 as a functional driver of proliferation, invasion, and migration beyond a single tumor type.

    Evidence Stable knockdown with colony formation, transwell, wound healing, and flow cytometry assays in glioma lines

    PMID:38467767

    Open questions at the time
    • Downstream effectors in glioma not identified
    • No in vivo confirmation reported
  9. 2025 Medium

    Identifying PSMB2 as a direct engagement partner in VCP/p97-directed degradation of a SUMO1-modified substrate revealed a ubiquitin-independent proteolytic route involving this subunit.

    Evidence Co-IP, SUMOylation-motif mutagenesis, fluorescent virion tracking, and VCP depletion in a CSFV uncoating model

    PMID:41288382

    Open questions at the time
    • Generality of SUMO1-VCP-PSMB2 degradation beyond viral Core protein unknown
    • Whether PSMB2 contributes catalytically or as a docking site not resolved
  10. 2025 Low

    A regulatory axis study placed PSMB2 as the downstream effector of a LINC00339/miR-671-5p circuit modulating cardiomyocyte injury.

    Evidence qRT-PCR, reporter and viability/apoptosis assays with overexpression in H/R-injured AC16 cardiomyocytes

    PMID:40143635

    Open questions at the time
    • Direct miRNA-PSMB2 binding not biochemically confirmed in the available evidence
    • Mechanism connecting PSMB2 to cardioprotection not defined
  11. 2026 Low

    Target-engagement profiling proposed PSMB2 as a direct binding target of an anti-inflammatory small molecule, raising it as a druggable proteasome subunit.

    Evidence DIA-CETSA in macrophages with molecular docking and dynamics simulations

    PMID:41939900

    Open questions at the time
    • Binding site not confirmed by mutagenesis or reconstitution
    • Functional consequence of compound binding to PSMB2 not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • How PSMB2 dosage mechanistically couples to NRF1 activation, ARID1A synthetic lethality, and SUMO1-VCP-directed degradation, and whether these reflect a shared subunit-specific function or general proteasome assembly, remains unresolved.
  • No structural model of PSMB2 within the assembled core in these contexts
  • No demonstration that observed phenotypes are PSMB2-specific versus generic core-subunit loss

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 2
Pathway
R-HSA-392499 Metabolism of proteins 3
Partners
PSMA7PSMD2VCP
Complex memberships
20S proteasome core26S proteasome

Evidence

Reading pass · 11 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 PSMB2 (C7-I) was identified as one of 17 protein subunits of the mouse 20S proteasome core; its identity was verified by two-dimensional NEPHGE-PAGE using specific antisera, establishing it as a structural beta subunit of the 20S proteolytic core. cDNA cloning, 2D gel electrophoresis (NEPHGE-PAGE), immunological verification with antisera Immunogenetics Medium 10436176
1997 The PSMB2 gene was mapped by fluorescence in situ hybridization to human chromosome band 1p34.2, and its independent chromosomal location from other beta subunit genes is consistent with independent regulation of expression and a role for proteasome assembly in coordinating the complex. Fluorescence in situ hybridization (FISH) Genomics Medium 9344661
2009 PSMB2 was identified as a gene capable of inducing oncogenic focus formation in a retroviral expression library screen using 3T3 fibroblasts, suggesting a transforming/oncogenic activity for PSMB2 in ovarian carcinogenesis. Retroviral expression library focus formation assay International journal of oncology Low 19787249
2018 NUDT21 knockdown increases usage of the proximal polyadenylation site in PSMB2 3' UTR, resulting in a shortened 3' UTR and marked increase in PSMB2 expression; knockdown of PSMB2 in turn suppressed HCC cell proliferation and invasion, placing PSMB2 downstream of the NUDT21-regulated alternative polyadenylation pathway. Global APA site profiling, NUDT21 knockdown, PSMB2 knockdown, cell proliferation and invasion assays Oncogene Medium 29780166
2011 RNAi silencing of PSMB2 in multiple myeloma cells synergistically potentiated the growth-inhibitory effects of bortezomib, identifying PSMB2 as a proteasome subunit whose suppression sensitizes myeloma cells to proteasome inhibition. Genome-wide RNAi screen with siRNA library in MM cells, proliferation assay with bortezomib Blood Medium 21289309
2022 PSMB2 knockdown in gastric cancer cells suppressed proteasome activity, inhibited cell proliferation, promoted apoptosis, and blocked NRF1 activation; PSMB2 overexpression promoted proteasome activity and cell proliferation, effects reversed by proteasome inhibitor MG132. PSMB2 knockdown also inhibited tumor growth in vivo. siRNA knockdown and overexpression in gastric cancer cell lines, proteasome activity assay, EdU staining, TUNEL assay, tumor xenograft assay, Western blotting Cytotechnology Medium 36110152
2024 Stable PSMB2 knockdown in glioma cell lines weakened proliferation, invasion, and migration, establishing PSMB2 as a functional driver of glioma cell growth and invasiveness. Stable PSMB2 knockdown, plate colony formation assay, transwell assay, wound healing assay, flow cytometry, qPCR and Western blotting Scientific reports Medium 38467767
2025 In a CSFV uncoating model, PSMB2 (along with PSMD2) was identified as a direct engagement partner for VCP/p97-directed proteasomal degradation of SUMO1-modified viral Core protein; this SUMOylation-dependent, ubiquitin-independent proteolytic mechanism was essential for viral uncoating, demonstrating that PSMB2 can mediate SUMO1-VCP-dependent substrate degradation. Co-immunoprecipitation, site-directed mutagenesis of SUMOylation motif, fluorescent virion tracking (molecular beacon and quantum dot labeling), VCP depletion assays Journal of virology Medium 41288382
2026 Drug affinity responsive target stability (CETSA) profiling in macrophages identified PSMB2 (along with PSMA7) as a direct binding target stabilized by the anti-inflammatory compound Handelin, suggesting physical interaction between Handelin and the PSMB2 subunit of the 26S proteasome. DIA-CETSA (drug affinity responsive target stability with data-independent acquisition mass spectrometry), molecular docking and dynamics simulations Frontiers in immunology Low 41939900
2023 In ARID1A-deficient iPSCs, CRISPRi whole-genome screen identified PSMB2 as a selective dependency, and this was replicated by pharmacological proteasome inhibition, establishing a synthetic lethal/dosage-sensitive interaction between ARID1A loss and PSMB2 function. Whole-genome CRISPRi screen in iPSCs, pharmacological proteasome inhibition (replication experiment) Stem cell reports Medium 37028423
2025 In H/R-injured cardiomyocytes, PSMB2 was identified as a downstream target gene of miR-671-5p; LINC00339 negatively regulated miR-671-5p, leading to increased PSMB2 expression, and PSMB2 overexpression inhibited the cardioprotective effect of sevoflurane postconditioning. This places PSMB2 as the effector in a LINC00339/miR-671-5p/PSMB2 regulatory axis modulating cardiomyocyte injury. qRT-PCR, luciferase reporter assay (implied by miRNA-target interaction), cell viability and apoptosis assays, overexpression experiments in AC16 cells Journal of biochemical and molecular toxicology Low 40143635

Source papers

Stage 0 corpus · 40 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 AGR2 is a novel surface antigen that promotes the dissemination of pancreatic cancer cells through regulation of cathepsins B and D. Cancer research 125 21948970
2018 NUDT21 negatively regulates PSMB2 and CXXC5 by alternative polyadenylation and contributes to hepatocellular carcinoma suppression. Oncogene 91 29780166
2011 RNAi screen of the druggable genome identifies modulators of proteasome inhibitor sensitivity in myeloma including CDK5. Blood 91 21289309
2008 Comparative analysis of transcriptional profiling of CD3+, CD4+ and CD8+ T cells identifies novel immune response players in T-cell activation. BMC genomics 90 18485203
2006 The influence of follicle size, FSH-enriched maturation medium, and early cleavage on bovine oocyte maternal mRNA levels. Molecular reproduction and development 77 16894554
2016 Identification of Differentially Expressed Genes through Integrated Study of Alzheimer's Disease Affected Brain Regions. PloS one 73 27050411
2019 Upregulation of Proteolytic Pathways and Altered Protein Biosynthesis Underlie Retinal Pathology in a Mouse Model of Alzheimer's Disease. Molecular neurobiology 52 30707393
2010 A new tick Kunitz type inhibitor, Amblyomin-X, induces tumor cell death by modulating genes related to the cell cycle and targeting the ubiquitin-proteasome system. Toxicon : official journal of the International Society on Toxinology 51 20570593
2018 Quercetin Prevents In Vivo and In Vitro Myocardial Hypertrophy Through the Proteasome-GSK-3 Pathway. Cardiovascular drugs and therapy 39 29435775
2014 Apigenin manipulates the ubiquitin-proteasome system to rescue estrogen receptor-β from degradation and induce apoptosis in prostate cancer cells. European journal of nutrition 39 25408199
2017 Elevated transcriptional levels of aldolase A (ALDOA) associates with cell cycle-related genes in patients with NSCLC and several solid tumors. BioData mining 38 28191039
1999 The complete primary structure of mouse 20S proteasomes. Immunogenetics 34 10436176
2015 Genetic polymorphisms associated with increased risk of developing chronic myelogenous leukemia. Oncotarget 30 26474455
2022 Imperfect guide-RNA (igRNA) enables CRISPR single-base editing with ABE and CBE. Nucleic acids research 27 35349689
2022 Genome-Wide Association Study of Egg-Laying Traits and Egg Quality in LingKun Chickens. Frontiers in veterinary science 26 35795788
2006 Differential expression of genes encoding constitutive and inducible 20S proteasomal core subunits in the testis and epididymis of theophylline- or 1,3-dinitrobenzene-exposed rats. Biology of reproduction 26 16988215
2009 Screening for genetic abnormalities involved in ovarian carcinogenesis using retroviral expression libraries. International journal of oncology 19 19787249
2015 The Orthology Clause in the Next Generation Sequencing Era: Novel Reference Genes Identified by RNA-seq in Humans Improve Normalization of Neonatal Equine Ovary RT-qPCR Data. PloS one 18 26536597
2015 Identification and comparison of gonadal transcripts of testis and ovary of adult common carp Cyprinus carpio using suppression subtractive hybridization. Theriogenology 15 25772851
1997 Genetic relationships of the genes encoding the human proteasome beta subunits and the proteasome PA28 complex. Genomics 14 9344661
2022 Luteolin Attenuates Diabetic Myocardial Hypertrophy by Inhibiting Proteasome Activity. Pharmacology 12 36423586
2010 Proteome alterations of cortex and hippocampus tissues in mice subjected to vitamin A depletion. The Journal of nutritional biochemistry 12 21190828
2019 Bortezomib sensitivity is tissue dependent and high expression of the 20S proteasome precludes good response in malignant pleural mesothelioma. Cancer management and research 10 31576173
2024 PSMB2 plays an oncogenic role in glioma and correlates to the immune microenvironment. Scientific reports 9 38467767
2023 Optimized whole-genome CRISPR interference screens identify ARID1A-dependent growth regulators in human induced pluripotent stem cells. Stem cell reports 9 37028423
2020 Host-Viral Interactions Revealed among Shared Transcriptomics Signatures of ARDS and Thrombosis: A Clue into COVID-19 Pathogenesis. TH open : companion journal to thrombosis and haemostasis 9 33354650
2023 Screening of Lymphoma Radiotherapy-Resistant Genes with CRISPR Activation Library. Pharmacogenomics and personalized medicine 8 36743888
2021 Shared Molecular Mechanisms between Atherosclerosis and Periodontitis by Analyzing the Transcriptomic Alterations of Peripheral Blood Monocytes. Computational and mathematical methods in medicine 8 34899963
2022 PSMB2 knockdown suppressed proteasome activity and cell proliferation, promoted apoptosis, and blocked NRF1 activation in gastric cancer cells. Cytotechnology 7 36110152
2021 Effectiveness of bortezomib and temozolomide for eradication of recurrent human glioblastoma cells, resistant to radiation. Progress in brain research 7 34689859
2023 Zonisamide attenuates pressure overload-induced myocardial hypertrophy in mice through proteasome inhibition. Acta pharmacologica Sinica 6 38097716
2014 Chronic schizophrenia is associated with over-expression of the interleukin-2 receptor gamma gene. Psychiatry research 6 24713359
2024 The Proteomic Analysis of Chronic Migraine Exosomes Reveals Disease Patterns and Potential Biomarkers. Molecular neurobiology 5 39066974
2023 Cathelicidin Antimicrobial Peptide Acts as a Tumor Suppressor in Hepatocellular Carcinoma. International journal of molecular sciences 5 37958632
2025 METTL14 Regulates the Expression of Genes Related to Interferon, Interleukin and MHC Class I in Nasopharyngeal Carcinoma Cells. Cancer medicine 2 41316520
2023 Genome-wide siRNA screens identify RBBP9 function as a potential target in Fanconi anaemia-deficient head-and-neck squamous cell carcinoma. Communications biology 2 36639418
2025 Sevoflurane Mediates LINC00339/miR-671-5p/PSMB2 Axis to Improve Cardiomyocytes Against Hypoxia/Reoxygenation Injury. Journal of biochemical and molecular toxicology 1 40143635
2026 Multi-omic profiling converges on proteasome subunits PSMA7/PSMB2 as targets of the sepsis-protective agent Handelin. Frontiers in immunology 0 41939900
2025 Bronchoalveolar lavage proteomics in exacerbation of bronchiectasis. BMC pulmonary medicine 0 41034841
2025 SUMOylation-dependent degradation of nucleocapsid is responsible for Pestivirus uncoating. Journal of virology 0 41288382

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