The cytokine-inducible zinc finger protein A20 inhibits IL-1-induced NF-κB activation at the level of TRAF6

Heyninck, Karen; Beyaert, Rudi

doi:10.1016/s0014-5793(98)01645-7

Cited by 169NF-κB Signaling PathwaysImmune Response and InflammationSignaling Pathways in Disease

The cytokine-inducible zinc finger protein A20 inhibits IL-1-induced NF-κB activation at the level of TRAF6

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Heyninck, Karen, Beyaert, Rudi·1999·FEBS Letters

DOI 10.1016/s0014-5793(98)01645-7

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Abstract

The zinc finger protein A20 is encoded by an immediate early response gene whose expression is induced by different inflammatory stimuli, including interleukin‐1 (IL‐1). Gene induction by IL‐1 is mediated by activation of the transcription factor NF‐κB, and requires the signal adapter protein TRAF6. The latter interacts with the NF‐κB‐inducing kinase NIK, which is believed to be part of the IκB kinase complex. Expression of A20 potently inhibits IL‐1‐induced NF‐κB activation by an unknown mechanism. Inhibition of IL‐1‐induced NF‐κB activation was found to be mediated by the C‐terminal zinc finger‐containing domain of A20. More importantly, we present evidence that A20 interferes with IL‐1‐induced NF‐κB activation at the level of TRAF6, upstream of NIK. Moreover, A20 was shown to directly interact with TRAF6.

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NF-κB is involved in gene expression of TNF-α and IL-1β in human monocytes and macrophages and HL-60 cells, and the effect of zinc in inhibiting gene expression of TNF-α and IL-1β is cell specific.
“Nuclear factor-B is involved in the gene expression of TNF-␣ and IL-1␤ in monocytes and macrophages in humans and HL-60 cells, and the effect of zinc in inhibiting the gene expression of TNF-␣ and IL-1␤ is cell specific (20 -25).”
From Zinc supplementation decreases incidence of infections in the elderly: effect of zinc on generation of cytokines and oxidative stress (2007) · cites this paper as [23]

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Identification of a Novel A20-binding Inhibitor of Nuclear Factor-κB Activation Termed ABIN-2
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A20 INHIBITS NF-κB ACTIVATION DOWNSTREAM OF MULTIPLE MAP3 KINASES AND INTERACTS WITH THE IκB SIGNALOSOME
Zetoune, F. S., Murthy, A. R., Shao, Z., Hlaing, T., Zeidler, M. G., Li, Y., & Vincenz, C. (2001) · Cytokine · doi:10.1006/cyto.2001.0921 · Cited by 45 · see citing works

Authors: Heyninck, K., & Beyaert, R.
Affiliations: Vlaams Instituut voor Biotechnologie (BE)
Corresponding author: Beyaert, Rudi
ORCID: Heyninck, Karen
Beyaert, Rudi
Venue: FEBS Letters
Publisher: Wiley
Published: 1999-01-15
Volume: 442
Issue: 2-3
Pages: 147-150
ISSN: 0014-5793 (ISSN-L)
1873-3468
DOI: 10.1016/s0014-5793(98)01645-7
OpenAlex: W2054142977
Cited by: 169
References: 28
Citations by year: 2024: 2 · 2023: 4 · 2022: 2 · 2021: 3 · 2020: 7 · 2019: 9 · 2018: 5 · 2017: 8 · 2016: 5 · 2015: 4 · 2014: 12 · 2013: 8 · 2012: 12
FWCI: 3.12
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor, 5 d)
Locations: FEBS Letters (publishedVersion)
PubMed (publishedVersion)
Ghent University Academic Bibliography (Ghent University) (submittedVersion)
Funders: Vlaamse regering
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
Keywords: A20, zinc finger proteins, interleukin-1, NF-κB activation, TRAF6, NIK, IκB kinase complex, protein-protein interaction, cytokine-induced gene expression
MeSH terms: Tumor Necrosis Factor alpha-Induced Protein 3, NF-kappaB-Inducing Kinase, Cell Line, DNA-Binding Proteins, Gene Expression Regulation, Humans, Interleukin-1, Kidney, Nuclear Proteins, Precipitin Tests, Proteins, Transfection, Tumor Necrosis Factor-alpha, Blotting, Western, Signal Transduction, Transcriptional Activation, NF-kappa B, Zinc Fingers, Protein Serine-Threonine Kinases, Sequence Deletion, Intracellular Signaling Peptides and Proteins, TNF Receptor-Associated Factor 1, TNF Receptor-Associated Factor 2, TNF Receptor-Associated Factor 6

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The cytokine-inducible zinc finger protein A20 inhibits IL-1-induced NF-κB activation at the level of TRAF6

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