title: Subunit specific inhibitors of proteasomes and their potential for immunomodulation.
abstract: Specialized variants of the constitutive 20S proteasome in the immune system like the immunoproteasomes and the thymoproteasome contain active site-bearing subunits which differ in their cleavage priorities and substrate binding pockets. The immunoproteasome plays a crucial role in antigen processing and for the differentiation of pro-inflammatory T helper cells which are involved in the pathogenesis of autoimmunity. Selective inhibitors of the immunoproteasome and constitutive proteasome have recently been generated which interfere with the development and progression of autoimmune diseases. Here we describe these inhibitors and their therapeutic potential as predicted from preclinical models.
authors.affiliation: Department of Pharmacology & Toxicology, Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, One Medical Center Drive, Lebanon, NH 03756, USA. Electronic address: Alexei.F.Kisselev@Dartmouth.EDU.
authors.forename: Alexei F
authors.initials: AF
authors.lastname: Kisselev
authors.affiliation: Division of Immunology, Department of Biology, University of Konstanz, D-78457 Konstanz, Germany; Biotechnology Institute Thurgau (BITg) at the University of Konstanz, CH-8280 Kreuzlingen, Switzerland. Electronic address: Marcus.Groettrup@uni-konstanz.de.
authors.forename: Marcus
authors.initials: M
authors.lastname: Groettrup
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D046988:Proteasome Endopeptidase Complex / Q000276:immunology*; D061988:Proteasome Inhibitors / Q000494:pharmacology*; D013379:Substrate Specificity
chemical_list: D007155:Immunologic Factors; D061988:Proteasome Inhibitors; D046988:Proteasome Endopeptidase Complex