title: Emerging roles of immunoproteasomes beyond MHC class I antigen processing.
abstract: The proteasome is a multi-catalytic protein complex whose primary function is the degradation of abnormal or foreign proteins. Upon exposure of cells to interferons (IFNs), the β1i/LMP2, β2i/MECL-1, and β5i/LMP7 subunits are induced and incorporated into newly synthesized immunoproteasomes (IP), which are thought to function solely as critical players in the optimization of the CD8(+) T-cell response. However, the observation that IP are present in several non-immune tissues under normal conditions and/or following pathological events militates against the view that its role is limited to MHC class I presentation. In support of this concept, the recent use of genetic models deficient for β1i/LMP2, β2i/MECL-1, or β5i/LMP7 has uncovered unanticipated functions for IP in innate immunity and non-immune processes. Herein, we review recent data in an attempt to clarify the role of IP beyond MHC class I epitope presentation with emphasis on its involvement in the regulation of protein homeostasis, cell proliferation, and cytokine gene expression.
authors.affiliation: Institut für Biochemie, Charité-Universitätsmedizin Berlin Campus CVK, Germany.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Ebstein
authors.forename: Peter-Michael
authors.initials: PM
authors.lastname: Kloetzel
authors.forename: Elke
authors.initials: E
authors.lastname: Krüger
authors.forename: Ulrike
authors.initials: U
authors.lastname: Seifert
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D049109:Cell Proliferation; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D005786:Gene Expression Regulation; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000502:physiology*; D011506:Proteins / Q000378:metabolism; D015398:Signal Transduction; D013312:Stress, Physiological
chemical_list: D016207:Cytokines; D015395:Histocompatibility Antigens Class I; D011506:Proteins; D046988:Proteasome Endopeptidase Complex