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PI31 is a modulator of proteasome formation and antigen processing.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Kloetzel, Peter-m Sijts, Alice J. A. M. Standera, Sybille Zaiss, Dietmar M. W.
Description	Author Affiliation: Zaiss DM ( Institute of Biochemistry, Medical Faculty Charité, Humboldt University, D-10117 Berlin, Germany.);
Abstract	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.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	22
Volume Number	99
Language	English
Publisher	National Academy of Sciences
Publisher Date	2002-10-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Adjuvants, Immunologic Antigen Presentation Immunology Cysteine Endopeptidases Biosynthesis Cysteine Proteinase Inhibitors Histocompatibility Antigens Class I Multienzyme Complexes Proteins Animals Cell Line Genetics Endoplasmic Reticulum Epitopes, T-Lymphocyte Interferon-gamma Mice Nuclear Envelope Proteasome Endopeptidase Complex T-Lymphocytes, Cytotoxic Up-Regulation Research Support, Non-U.S. Gov't Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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