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.
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MG132 is a proteosome inhibitor that inhibits NF-κB signaling, while LY294002 is a PI3K/Akt signaling antagonist.
“MG132 is a proteosome inhibitor, which inhibits NF-κB signaling (31), while LY294002 is a PI3K/Akt signaling antagonist.”
From Reprogramming of three-dimensional microenvironments for in vitro hair follicle induction (2022) · cites this paper as [31]
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- Authors
- Nakajima, S., Kato, H., Takahashi, S., Johno, H., & Kitamura, M.
- Affiliations
- University of Yamanashi (JP)
- Corresponding author
- Kitamura, Masanori
- Venue
- FEBS Letters
- Publisher
- Wiley
- Published
- 2011-05-27
- Volume
- 585
- Issue
- 14
- Pages
- 2249-2254
- ISSN
- 0014-5793 (ISSN-L)
- OpenAlex
- W2101621398
- Cited by
- 46
- References
- 27
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 4 · 2023: 4 · 2022: 3 · 2021: 5 · 2020: 1 · 2019: 3 · 2018: 2 · 2017: 4 · 2016: 3 · 2015: 4 · 2014: 4 · 2013: 2 · 2012: 3
- FWCI
- 0.98
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- FEBS Letters (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology, Japan (20390235)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Endoplasmic Reticulum Stress and Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
- Keywords
- NF-κB inhibition, MG132, proteasome inhibitors, endoplasmic reticulum stress, C/EBPβ, IκB degradation, translational regulation
- MeSH terms
- Animals, Cell Line, Endoplasmic Reticulum, Leupeptins, Stress, Physiological, Transcriptional Activation, Cysteine Proteinase Inhibitors, NF-kappa B, CCAAT-Enhancer-Binding Protein-beta, Rats, Unfolded Protein Response
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