Cited by 267NF-κB Signaling PathwaysSignaling Pathways in DiseaseImmune Response and Inflammation

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Beyond IκBs: alternative regulation of NF‐KB activity

Neumann, Manfred, Naumann, Michael·2007·The FASEB Journal

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Abstract

The transcription factor nuclear factor-kappa B (NF-kappaB) is a crucial regulator of many physiological and patho-physiological processes, including control of the adaptive and innate immune responses, inflammation, proliferation, tumorigenesis, and apoptosis. Thus, the tight regulation of NF-kappaB activity within a cell is extremely important. The central mechanism of NF-kappaB regulation is the signal-induced proteolytic degradation of a family of cytoplasmic inhibitors of NF-kappaB, the IkappaBs. However, with the discovery of an IkappaB-independent noncanonical or "alternative" pathway of NF-kappaB activation, the importance of other regulatory mechanisms responsible for the fine-tuning of NF-kappaB became clear. Post-translational modification, especially phosphorylation, of the Rel proteins, of which dimeric NF-kappaB is composed, are such alternative regulatory mechanisms. The best analyzed example is RelA phosphorylation, which takes place at specific amino acids resulting in distinct functional changes of this gene regulatory protein. The interaction of NF-kappaB with other proteins such as glucocorticoid receptors is very important for the regulation of NF-kappaB activity. Recently, exciting new concepts of IkappaB-independent NF-kappaB control like dimer exchange and nucleolar sequestration of RelA have been described, indicating that many aspects of NF-kappaB control are waiting to be discovered.

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Authors: Neumann, M., & Naumann, M.
Affiliations: Otto-von-Guericke-Universität Magdeburg (DE)
ORCID: Naumann, Michael
Venue: The FASEB Journal
Publisher: Wiley
Published: 2007-04-12
Volume: 21
Issue: 11
Pages: 2642-2654
ISSN: 0892-6638 (ISSN-L)
1530-6860
DOI: 10.1096/fj.06-7615rev
OpenAlex: W1792654735
Cited by: 267
References: 100
Citations by year: 2026: 4 · 2025: 7 · 2024: 11 · 2023: 14 · 2022: 11 · 2021: 14 · 2020: 5 · 2019: 9 · 2018: 8 · 2017: 16 · 2016: 12 · 2015: 11 · 2014: 11 · 2013: 12 · 2012: 12
FWCI: 2.24
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: The FASEB Journal (publishedVersion)
PubMed (publishedVersion)
Funders: Deutsche Forschungsgemeinschaft (NE608/3–2, NA292/7–3)
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: NF-κB, p65 phosphorylation, Rel proteins, post-translational modification, glucocorticoid receptor, nucleolar sequestration, transcription factor regulation, inflammation, immune response
MeSH terms: Animals, DNA-Binding Proteins, Humans, Phosphorylation, Ubiquitins, Signal Transduction, NF-kappa B, I-kappa B Proteins, Transcription Factor RelA

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Beyond IκBs: alternative regulation of NF‐KB activity

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