Publication date: March 2017
Source:Molecular Immunology, Volume 83
Author(s): Annegret Bitzer, Michael Basler, Daniel Krappmann, Marcus Groettrup
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.
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