PI31 is a modulator of proteasome formation and antigen processing.
Regulation of the proteasome system, which is responsible for the generation of most MHC class I-bound peptides, occurs through the interaction of the 20S proteasome with several regulatory proteins. One of these is PI31, which acts in vitro as an inhibitor of proteasome activity. Here, we demonstrate that, rather than inhibiting proteasome function, PI31 acts as a selective modulator of the proteasome-mediated steps in MHC class I antigen processing. Overexpression of PI31 in mouse embryonic cells has no impact on proteasome-mediated proteolysis. Instead, PI31, which localizes at the nuclear envelope/endoplasmic reticulum membrane, selectively interferes with the maturation of immunoproteasome precursor complexes. Consequently, overexpression of PI31 abrogates MHC class I presentation of an immunoproteasome-dependent cytotoxic T lymphocyte epitope and reduces the surface MHC class I levels on IFN-gamma-treated mouse embryonic cells. Thus, PI31 represents a cellular regulator of proteasome formation and of proteasome-mediated antigen processing.
Zaiss
Dietmar M W
DM
Institute of Biochemistry, Medical Faculty Charité, Humboldt University, D-10117 Berlin, Germany.
Standera
Sybille
S
Kloetzel
Peter-M
PM
Sijts
Alice J A M
AJ
D000276:Adjuvants, Immunologic; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000096:biosynthesis*; D015853:Cysteine Proteinase Inhibitors / Q000235:genetics / Q000276:immunology*; D004721:Endoplasmic Reticulum; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology; D051379:Mice; D009097:Multienzyme Complexes / Q000096:biosynthesis*; D009685:Nuclear Envelope; D046988:Proteasome Endopeptidase Complex; D011506:Proteins; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology
D000276:Adjuvants, Immunologic; D015853:Cysteine Proteinase Inhibitors; D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; D009097:Multienzyme Complexes; C121623:PSMF1 protein, human; D011506:Proteins; D007371:Interferon-gamma; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex