Cited by 1,434NF-κB Signaling PathwaysSignaling Pathways in DiseaseImmune Response and Inflammation

Control of IκB-α Proteolysis by Site-Specific, Signal-Induced Phosphorylation

Brown, Keith, Gerstberger, Susan, Carlson, Louise, Franzoso, Guido, Siebenlist, Ulrich·1995·Science

Abstract

I kappa B-alpha inhibits transcription factor NF-kappa B by retaining it in the cytoplasm. Various stimuli, typically those associated with stress or pathogens, rapidly inactivate I kappa B-alpha. This liberates NF-kappa B to translocate to the nucleus and initiate transcription of genes important for the defense of the organism. Activation of NF-kappa B correlates with phosphorylation of I kappa B-alpha and requires the proteolysis of this inhibitor. When either serine-32 or serine-36 of I kappa B-alpha was mutated, the protein did not undergo signal-induced phosphorylation or degradation, and NF-kappa B could not be activated. These results suggest that phosphorylation at one or both of these residues is critical for activation of NF-kappa B.

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Crossref · 10.1126/science.7878466

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18 of 18 references verified0 citation errors · 0 not checkable

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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
Brown, K., Gerstberger, S., Carlson, L., Franzoso, G., & Siebenlist, U.
Affiliations
National Institutes of Health (US)
Venue
Science
Published
1995-03-10
Volume
267
Issue
5203
Pages
1485-1488
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
OpenAlex
W2070853191
Cited by
1,434
References
18
Citations by year
2026: 5 · 2025: 12 · 2024: 6 · 2023: 9 · 2022: 11 · 2021: 12 · 2020: 14 · 2019: 15 · 2018: 10 · 2017: 21 · 2016: 26 · 2015: 21 · 2014: 23 · 2013: 25 · 2012: 33
FWCI
49.95
Type
journal article
Language
en
Open access
closed
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Keywords
IκBα, NF-κB activation, protein phosphorylation, transcriptional regulation
MeSH terms
NF-KappaB Inhibitor alpha, Amino Acid Sequence, Animals, Cell Line, DNA-Binding Proteins, Humans, Molecular Sequence Data, Mutation, Phosphorylation, T-Lymphocytes, Tetradecanoylphorbol Acetate, Transfection, Tumor Necrosis Factor-alpha, Signal Transduction, Transcriptional Activation, Ionomycin, NF-kappa B, Point Mutation, I-kappa B Proteins, Mice

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