Immunoproteasome subunit deficiency has no influence on the canonical pathway of NF-κB activation.
Activation of the pro-inflammatory transcription factor NF-κB requires signal-induced proteasomal degradation of the inhibitor of NF-κB (IκB) in order to allow nuclear translocation. Most cell types are capable of expressing two types of 20S proteasome core particles, the constitutive proteasome and immunoproteasome. Inducible under inflammatory conditions, the immunoproteasome is mainly characterized through an altered cleavage specificity compared to the constitutive proteasome. However, the question whether immunoproteasome subunits affect NF-κB signal transduction differently from constitutive subunits is still up for debate. To study the effect of immunoproteasomes on LPS- or TNF-α-induced NF-κB activation, we used IFN-γ stimulated peritoneal macrophages and mouse embryonic fibroblasts derived from mice deficient for the immunoproteasome subunits low molecular mass polypeptide (LMP) 2, or LMP7 and multicatalytic endopeptidase complex-like 1 (MECL-1). Along the canonical signaling pathway of NF-κB activation no differences in the extent and kinetic of IκB degradation were observed. Neither the nuclear translocation and DNA binding of NF-κB nor the production of the NF-κB dependent cytokines TNF-α, IL-6, and IL-10 differed between immunoproteasome deficient and proficient cells. Hence, we conclude that immunoproteasome subunits have no specialized function for canonical NF-κB activation.
Division of Immunology, Department of Biology, University of Konstanz, D-78457 Konstanz, Germany.
Annegret
A
Bitzer
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.
Michael
M
Basler
Research Unit Cellular Signal Integration, Institute of Molecular Toxicology and Pharmacology, Helmholtz Zentrum München - German Research Center for Environmental Health, Ingolstädter Landstr. 1, D-85764 Neuherberg, Germany.
Daniel
D
Krappmann
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.
Marcus
M
Groettrup
D000818:Animals; D015153:Blotting, Western; D003546:Cysteine Endopeptidases / Q000172:deficiency / Q000276:immunology; D024202:Electrophoretic Mobility Shift Assay; D004789:Enzyme Activation / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000276:immunology*; D017737:Macrophages, Peritoneal / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000276:immunology* / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000172:deficiency / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology
D016328:NF-kappa B; C071313:LMP-2 protein; D003546:Cysteine Endopeptidases; C077436:LMP7 protein; D046988:Proteasome Endopeptidase Complex; C490920:Psmb10 protein, mouse
Immunoproteasome; Inflammation; LMP2; LMP7; NF-κB