Interferon-gamma induces different subunit organizations and functional diversity of proteasomes.
To obtain information on the role of proteasomes in the immune system, we examined the effect of a major immunomodulatory cytokine, gamma interferon (IFN-gamma), on the expressions, structures, and functions of proteasomes. IFN-gamma greatly increased the levels of the mRNAs encoding LMP2 and LMP7, putative immuno-proteasome subunits encoded by genes within the class II MHC region, and these two subunits synthesized were assembled completely into the proteasomal multi-subunit complex in various types of human cells. The subunit organization of proteasome changed in response to IFN-gamma stimulation, due to assembly of newly synthesized subunits through up- and down-expressions of at least 6 proteasome genes including LMP2/LMP7 without change in the structure of pre-existing proteasomes. Interestingly, IFN-gamma dramatically stimulated the trypsin-like and chymotrypsin-like activities of the multifunctional proteasome and depressed the peptidylglutamyl-peptide-hydrolyzing activity, without affecting the activity for ATP-, ubiquitin-dependent proteolysis. These results indicate that IFN-gamma modifies not only the structural organization of the proteasome, but also its functions. Based on these findings, we discuss the role in the antigen processing/presentation pathway of proteasomes with functional diversity acquired through alteration of their subunit assembly in response to IFN-gamma stimulation.
Aki
M
M
Department of Urology, School of Medicine, University of Tokushima.
Shimbara
N
N
Takashina
M
M
Akiyama
K
K
Kagawa
S
S
Tamura
T
T
Tanahashi
N
N
Yoshimura
T
T
Tanaka
K
K
Ichihara
A
A
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000595:Amino Acid Sequence; D003110:Colonic Neoplasms; D003546:Cysteine Endopeptidases / Q000737:chemistry / Q000378:metabolism*; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D006868:Hydrolysis; D007371:Interferon-gamma / Q000494:pharmacology*; D007951:Leukemia, Myeloid; D008285:Major Histocompatibility Complex / Q000187:drug effects; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000737:chemistry / Q000378:metabolism*; D009693:Nucleic Acid Hybridization; D046988:Proteasome Endopeptidase Complex; D011506:Proteins / Q000737:chemistry / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured; D014452:Ubiquitins / Q000494:pharmacology
D015395:Histocompatibility Antigens Class I; D009097:Multienzyme Complexes; D011506:Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014452:Ubiquitins; C071313:LMP-2 protein; D007371:Interferon-gamma; D000255:Adenosine Triphosphate; D003546:Cysteine Endopeptidases; C077436:LMP7 protein; D046988:Proteasome Endopeptidase Complex