Cited by 128NF-κB Signaling PathwaysUbiquitin and proteasome pathwaysImmune Response and Inflammation

A pervasive role of ubiquitin conjugation in activation and termination of IκB kinase pathways

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Krappmann, Daniel, Scheidereit, Claus·2005·The EMBO Reports

Abstract

The nuclear factor (NF)-kappaB pathway is a paradigm for gene expression control by ubiquitin-mediated protein degradation. In stimulated cells, phosphorylation by the IkappaB kinase (IKK) complex primes NF-kappaB-inhibiting IkappaB molecules for lysine (Lys)-48-linked polyubiquitination and subsequent destruction by the 26S proteasome. However, recent studies indicate that the ubiquitin (Ub) system controls NF-kappaB pathways at many levels. Ub ligases are activated by different upstream signalling pathways, and they function as central regulators of IKK and c-Jun amino-terminal kinase activation. The assembly of Lys 63 polyUb chains provides docking surfaces for the recruitment of IKK-activating complexes, a reaction that is counteracted by deubiquitinating enzymes. Furthermore, Ub conjugation targets upstream signalling mediators as well as nuclear NF-kappaB for post-inductive degradation to limit the duration of signalling.

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  • Inflammatory signals such as LPS, pro-inflammatory cytokines, reactive oxygen species, advanced glycation end products, and oxidized LDL cause IKKβ phosphorylation; this phosphorylates IκBα, leading to its ubiquitination and degradation, which releases NF-κB to enter the nucleus and induce pro-inflammatory genes.

    “Extracellular inflammatory signals including lipopolysaccharide (LPS), pro-inflammatory cytokines, reactive oxygen species, advanced glycation end products, and oxidized low-density lipoprotein trigger the phosphorylation of IKKβ, which in turn phosphorylates IκBα for ubiquitination and degradation by proteasome [13–18].”

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Authors
Krappmann, D., & Scheidereit, C.
Affiliations
Max Delbrück Center (DE)
Corresponding author
Scheidereit, Claus
Venue
The EMBO Reports
Published
2005-04-01
Volume
6
Issue
4
Pages
321-326
ISSN
  • 1469-221X (ISSN-L)
  • 1469-3178
OpenAlex
W2169463874
Cited by
128
References
41
Citations by year
2026: 2 · 2025: 1 · 2024: 3 · 2023: 1 · 2022: 2 · 2021: 1 · 2020: 2 · 2019: 2 · 2017: 2 · 2016: 5 · 2015: 3 · 2014: 6 · 2013: 5 · 2012: 5
FWCI
1.47
Type
journal article
Language
en
Open access
Locations
  • EMBO Reports (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Site cant be reached (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Keywords
ubiquitin conjugation, NF-κB signaling, IκB kinase, IκB degradation, Lys63-linked polyubiquitination, E3 ubiquitin ligase, deubiquitinase, c-Jun N-terminal kinase, 26S proteasome, signal termination
MeSH terms
Enzyme Activation, Gene Expression Regulation, Humans, Models, Biological, Signal Transduction, NF-kappa B, Protein Serine-Threonine Kinases, Ubiquitin, I-kappa B Kinase

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