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Inhibition of NF‐κB by MG132 through ER stress‐mediated induction of LAP and LIP
Author(s) -
Nakajima Shotaro,
Kato Hironori,
Takahashi Shuhei,
Johno Hisashi,
Kitamura Masanori
Publication year - 2011
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2011.05.047
Subject(s) - mg132 , unfolded protein response , endoplasmic reticulum , proteasome inhibitor , nf κb , chemistry , proteasome , iκbα , microbiology and biotechnology , biology , apoptosis , biochemistry
Proteasome inhibitor MG132 blocks activation of NF‐κB by preventing degradation of IκB. In this report, we propose an alternative mechanism by which MG132 inhibits cytokine‐triggered NF‐κB activation. We found that MG132 induced endoplasmic reticulum (ER) stress, and attenuation of ER stress blunted the suppressive effect of MG132 on NF‐κB. Through ER stress, MG132 up‐regulated C / EBPβ mRNA transiently and caused sustained accumulation of its translational products liver activating protein (LAP) and liver‐enriched inhibitory protein (LIP), both of which were identified as suppressors of NF‐κB. Our results disclosed a novel mechanism underlying inhibition of NF‐κB by MG132.