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Updated: Aug 16, 2026
Preparation Of Neovascular Tissues from Human Glioma Tissues for Quantitative Proteomics Analysis of Tumor Angiogenesis
Published on: March 20, 2026
Characterization of the 20S proteasome in human glioblastomas
Marco Piccinini1, Maria Teresa Rinaudo, Annalisa Anselmino
1Department of Medicine and Experimental Oncology, Section of Biochemistry, University of Turin, Via Michelangelo n 27/b, 10126 Turin, Italy.
Abstract:
Proteasomes are multisubunit proteases involved in many cellular processes, including tumorigenesis and immune surveillance. In their catalytic core, the 20S proteasome, the beta1, beta2 and beta5 subunits show peptidylglutamyl peptide hydrolyzing (PGPH), trypsin-like and chymotrypsin-like activities, respectively. By IFN-gamma and TNFalpha stimulus, these subunits are replaced by their counterparts LMP2, MECL-1 and LMP7, defined inducible subunits, thus originating the immunoproteasome, and expression of the proteasome activator PA28 is enhanced. These modifications strengthen MHC-class I restricted peptide generation. The 20S proteasome has been detected immunohistochemically in formalin-fixed samples purified from fresh surgical specimens of 18 tumors (G20S) and from 8 samples of normal peritumoral tissue. The G20S, LMP2, MECL-1 and LMP7 increased in only 12 cases, along with unvaried trypsin-like and decreased PGPH and chymotrypsin-like activities; PA28 was unvaried in all 18 samples. The immunoproteasome alterations may represent an anomalous immunological attitude of glioblastomas.
Insights
Glioblastomas exhibit altered immunoproteasome composition, with increased specific subunits (LMP2, MECL-1, LMP7) but decreased catalytic activities. These changes suggest a unique immunological response in these brain tumors.
Area of Science:
- Immunology
- Molecular Biology
- Oncology
Background:
- Proteasomes are crucial for cellular processes, including immune surveillance and tumorigenesis.
- The 20S proteasome core contains catalytic subunits (beta1, beta2, beta5) with distinct enzymatic activities.
- Cytokine stimulation (IFN-gamma, TNFalpha) induces the immunoproteasome, enhancing MHC class I peptide generation.
Purpose of the Study:
- To investigate the presence and activity of proteasome subunits in glioblastoma tumors.
- To determine if immunoproteasome alterations are associated with glioblastoma's immunological profile.
Main Methods:
- Immunohistochemistry was used to detect proteasome subunits in formalin-fixed glioblastoma tissues and normal peritumoral samples.
- Enzymatic activities of proteasome subunits (PGPH, trypsin-like, chymotrypsin-like) were assessed.
- Expression levels of proteasome activator PA28 were evaluated.
Main Results:
- Increased expression of immunoproteasome subunits (LMP2, MECL-1, LMP7) was observed in 12 out of 18 glioblastoma samples.
- A decrease in PGPH and chymotrypsin-like activities, with unvaried trypsin-like activity, was noted.
- Proteasome activator PA28 expression remained unchanged across all samples.
Conclusions:
- Glioblastomas display altered immunoproteasome subunit composition and enzymatic activity.
- These modifications may indicate an anomalous immunological response characteristic of glioblastomas.
