title: Inhibition of NF-κB by MG132 through ER stress-mediated induction of LAP and LIP.
abstract: 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.
authors.affiliation: Department of Molecular Signaling, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo, Yamanashi, Japan.
authors.forename: Shotaro
authors.initials: S
authors.lastname: Nakajima
authors.forename: Hironori
authors.initials: H
authors.lastname: Kato
authors.forename: Shuhei
authors.initials: S
authors.lastname: Takahashi
authors.forename: Hisashi
authors.initials: H
authors.lastname: Johno
authors.forename: Masanori
authors.initials: M
authors.lastname: Kitamura
mesh_terms: D000818:Animals; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D007976:Leupeptins / Q000378:metabolism / Q000494:pharmacology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D013312:Stress, Physiological; D015533:Transcriptional Activation; D056811:Unfolded Protein Response
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; D015853:Cysteine Proteinase Inhibitors; D007976:Leupeptins; D016328:NF-kappa B; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde