PSMB2 Human
Description
Oncogenic Role in Glioma
Recent studies demonstrate PSMB2's clinical significance in neuro-oncology:
Prognostic Value
Analysis of 696 glioma patients revealed significant survival differences :
| PSMB2 Expression | Median OS (Months) | 5-Year Survival Rate |
|---|---|---|
| High | 15.2 | 8.7% |
| Low | 58.4 | 42.1% |
Multivariate Cox regression identified PSMB2 as an independent prognostic factor (HR=2.807, 95% CI 1.484–5.310, p=0.002) .
Pathogenic Mechanisms
Functional enrichment analyses link PSMB2 to key oncogenic pathways:
| Pathway | Enrichment Score | FDR q-value |
|---|---|---|
| Epithelial-Mesenchymal Transition | 2.31 | <0.001 |
| IL-6/JAK/STAT3 Signaling | 1.98 | 0.004 |
| Angiogenesis | 1.75 | 0.012 |
| G2M Checkpoint | 1.62 | 0.023 |
PSMB2 overexpression correlates with immune cell infiltration levels :
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Th2 cells (R=0.594, p<0.001)
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Macrophages (R=0.466, p<0.001)
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Neutrophils (R=0.349, p<0.001)
Diagnostic Utility
PSMB2 demonstrates stability as a reference gene in bronchoalveolar lavage cells for :
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Sarcoidosis (AUC=0.89)
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Interstitial lung disease (AUC=0.85)
Therapeutic Targeting
Preclinical data support PSMB2 inhibition strategies:
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shRNA knockdown reduces glioma cell proliferation by 62% (p<0.01)
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PSMB2-siRNA decreases invasion capacity by 41% (transwell assay)
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Recombinant PSMB2 (ENZ-204) enables targeted proteasome studies
Expression Patterns
The Human Protein Atlas documents PSMB2 distribution :
| Tissue | Expression Level | Clinical Correlation |
|---|---|---|
| Glioblastoma | High | Poor prognosis |
| Liver HCC | Moderate | Tumor progression |
| Ovarian Epithelium | Elevated | Chemoresistance |
| Normal Brain | Low | N/A |
Product Specs
RKCLEELQKR FILNLPTFSV RIIDKNGIHD LDNISFPKQG S.
Q&A
What are the core structural and functional characteristics of PSMB2 in human proteasomes?
PSMB2 is a 23 kDa beta subunit (β2) of the 20S proteasome core particle, encoded by the PSMB2 gene located at chromosome 1p34.2. It contributes to the assembly of two heptameric β-rings within the proteasome, forming a proteolytic chamber responsible for substrate degradation . Unlike the constitutive β1 and β5 subunits, PSMB2 lacks catalytic activity but plays a structural role in maintaining proteasome integrity. Its theoretical isoelectric point (pI) is 6.52, and it comprises 201 amino acids .
Methodological Note: To study PSMB2’s structural role, researchers often use cryo-electron microscopy (cryo-EM) or X-ray crystallography to resolve proteasome subunit arrangements. Functional assays (e.g., proteolytic activity measurements in β2-deficient cells) can confirm its non-catalytic role .
How does PSMB2 contribute to glioma progression and prognosis?
What experimental approaches validate PSMB2’s role in cancer progression?
To study PSMB2’s oncogenic potential, researchers employ:
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Stable Knockdown Models: Lentiviral shRNA constructs to silence PSMB2 in glioma cell lines (e.g., U87, U251), followed by assays for proliferation (plate colony formation), invasion (transwell), and migration (wound healing) .
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Proteomic Validation: Quantitative PCR and Western blotting to confirm PSMB2 mRNA/protein downregulation post-knockdown.
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Functional Enrichment: RNA-seq data analyzed via GO/KEGG to identify PSMB2-associated pathways (e.g., angiogenesis, immune response) .
Key Tools:
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Survival Analysis: Cox proportional hazards models to assess PSMB2’s prognostic value.
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Immune Microenvironment Profiling: ssGSEA and immune checkpoint gene correlation analyses to link PSMB2 to T cell infiltration or PD-1/PD-L1 expression .
How to address contradictions in PSMB2 expression data across studies?
Conflicting reports on PSMB2’s role (e.g., tumor suppressor vs. oncogene) may arise from heterogeneity in tumor types or experimental conditions. To resolve discrepancies:
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Meta-Analyses: Integrate multi-omic datasets (e.g., TCGA, GTEx) to normalize expression levels and account for batch effects.
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Stratification: Subgroup analyses by tumor grade (e.g., glioblastoma vs. low-grade glioma) or molecular subtypes (IDH wild/mutant) .
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Functional Validation: Use orthogonal assays (e.g., CRISPR-Cas9 knockout) to confirm PSMB2’s role in specific contexts.
Example: In glioma, PSMB2’s association with poor prognosis is consistent across TCGA and CGGA cohorts, but its role in other cancers (e.g., lung) may differ due to distinct proteasome dynamics .
What methodologies optimize PSMB2 as a biomarker or therapeutic target?
Biomarker Validation:
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Nomogram Construction: Integrate PSMB2 expression with clinical variables (WHO grade, IDH status, age) using Cox regression to predict 1/3/5-year OS .
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C-index Evaluation: Assess model accuracy (e.g., C-index >0.7 indicates strong predictive power) .
Therapeutic Targeting:
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Proteasome Inhibitor Sensitivity: Cross-reference PSMB2 expression with chemoresponse data (e.g., GDSC) to predict efficacy of proteasome inhibitors like bortezomib.
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Immune Checkpoint Synergy: Investigate PSMB2’s interaction with anti-PD-1 therapies using TIDE algorithms to predict response rates .
How does PSMB2 modulate the tumor immune microenvironment in glioma?
Data Correlation:
| Immune Cell Type | PSMB2 Correlation (R) | P-value |
|---|---|---|
| Th2 Cells | 0.594 | <0.001 |
| Macrophages | 0.466 | <0.001 |
| Neutrophils | 0.349 | <0.001 |
What challenges exist in studying PSMB2 in clinical samples?
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Heterogeneity: PSMB2 expression varies across tumor regions and patient cohorts, necessitating robust normalization (e.g., using RPL32 in BAL cells for lung diseases) .
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Assay Sensitivity: Detecting low-abundance PSMB2 mRNA/protein requires optimized qRT-PCR primers or antibodies validated via Western blot .
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Proteasome Dynamics: PSMB2’s structural role complicates its direct targeting; inhibitors may disrupt entire proteasome function, causing off-target effects .
How to design experiments to study PSMB2 in non-glioma cancers?
For cancers like lung or breast:
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Tissue-Specific Validation: Use PSMB2 as a reference gene for qRT-PCR in bronchoalveolar lavage (BAL) cells, as established in interstitial lung disease models .
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Oncogenic Pathway Mapping: Perform RNAi screens to identify PSMB2-dependent genes in specific cancer lines.
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Proteasome Subunit Interactions: Co-immunoprecipitation (Co-IP) to study PSMB2’s binding with other β-subunits (e.g., β1, β5) and assembly regulators .
What computational tools are essential for analyzing PSMB2’s biological role?
| Tool | Application |
|---|---|
| TCGA/CGGA Databases | Expression/prognosis correlation, survival analysis |
| GSEA (Broad Institute) | Pathway enrichment of PSMB2-associated genes |
| CIBERSORT/ImmuneDeconv | Quantification of immune cell infiltration |
| GDSC | Prediction of chemotherapeutic sensitivity based on PSMB2 expression |
| R Packages (survival, limma) | Cox regression, differential expression analysis |
What future directions exist for PSMB2 research?
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Mechanistic Studies: Elucidate PSMB2’s role in proteasome assembly and substrate specificity.
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Therapeutic Combinations: Test PSMB2 inhibitors with immunotherapies to exploit tumor-immune interactions.
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Biomarker Optimization: Refine nomograms for glioma prognosis and monitor PSMB2 during treatment.
Product Science Overview
Proteasome Subunit Beta Type 2 (PSMB2), also known as 20S proteasome subunit beta-4, is a crucial component of the proteasome complex in humans. This protein is encoded by the PSMB2 gene and plays a significant role in the degradation of intracellular proteins, which is essential for maintaining cellular homeostasis .
The human PSMB2 protein is composed of 201 amino acids and has a molecular weight of approximately 23 kDa . It is a non-catalytic component of the 20S core proteasome complex, which is involved in the proteolytic degradation of most intracellular proteins . The proteasome complex is responsible for various cellular processes, including the regulation of the cell cycle, modulation of signaling pathways, and removal of damaged or misfolded proteins .
PSMB2 is involved in numerous biological processes, including:
PSMB2 has been associated with various clinical conditions. For instance, it has shown stability in bronchoalveolar cells of the lung during certain clinical conditions such as interstitial lung disease and sarcoidosis . Additionally, diseases associated with PSMB2 include acute myeloid leukemia and Schimke immunoosseous dysplasia .
Recombinant human PSMB2 is often produced using Escherichia coli expression systems. The recombinant protein is typically purified to a high degree of purity (>90%) and is used in various research applications, including mass spectrometry and SDS-PAGE . The recombinant form of PSMB2 retains the functional properties of the native protein, making it a valuable tool for studying proteasome function and related cellular processes .
