Characterization of the 20S proteasome in human glioblastomas.
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.
Piccinini
Marco
M
Department of Medicine and Experimental Oncology, Section of Biochemistry, University of Turin, Via Michelangelo n 27/b, 10126 Turin, Italy.
Rinaudo
Maria Teresa
MT
Anselmino
Annalisa
A
Ramondetti
Cristina
C
Buccinnà
Barbara
B
Fiano
Valentina
V
Ghimenti
Chiara
C
Schiffer
Davide
D
D016543:Central Nervous System Neoplasms / Q000201:enzymology* / Q000473:pathology; D003546:Cysteine Endopeptidases / Q000378:metabolism; D005909:Glioblastoma / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008214:Lymphocytes / Q000201:enzymology / Q000473:pathology; D008264:Macrophages / Q000201:enzymology / Q000473:pathology; D017628:Microglia / Q000201:enzymology / Q000473:pathology; D009097:Multienzyme Complexes / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000302:isolation & purification / Q000378:metabolism*
D009097:Multienzyme Complexes; C071313:LMP-2 protein; D010447:Peptide Hydrolases; D003546:Cysteine Endopeptidases; C077436:LMP7 protein; C098948:PSMB10 protein, human; D046988:Proteasome Endopeptidase Complex