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Missing Pieces in the NF-κB Puzzle
Open accessAbstract
The regulation of the transcription factor NF-kappaB activity occurs at several levels including controlled cytoplasmic-nuclear shuttling and modulation of its transcriptional activity. A critical component in NF-kappaB regulation is the IkappaB kinase (IKK) complex. This review is focused on recent progress as well as unanswered questions regarding the regulation and function of NF-kappaB and IKK.
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“In the NF-κB system (e.g. [2020-2024]) (Fig 8), NF-κB is normally held inactive in the cytoplasm by binding to an inhibitor IκB (often IκBα). Pro-inflammatory cytokines such as TNF-α, LPS [2025-2030] and IL-1 [2031] act by binding to receptors at the cell surface and initiating signalling pathways that lead to the activation of a particular kinase, IκB kinase or IKK. This kinase phosphorylates the”
From Iron behaving badly: inappropriate iron chelation as a major contributor to the aetiology of vascular and other progressive inflammatory and degenerative diseases (2009) · cites this paper as [2020]
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BackgroundInfluentialTNF and IL-1 exhibit distinct ubiquitin requirements for inducing NEMO–IKK supramolecular structures
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“The classical NF-kB signaling pathway, which is activated by proinflammatory cytokines and pathogen-associated molecu- lar patterns (PAMPs), depends on inducible degradation of specific inhibitors, IkBs, which retain different NF-kB dimers in the cytoplasm (Ghosh and Karin, 2002).”
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“An IKK complex consists of two catalytic subunits, IKK-a and IKK-b, and a regulatory subunit, IKK-g, and is activated in a TNFdependent manner (Ghosh and Karin 2002).”
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Antigen-Receptor Signaling to Nuclear Factor κB
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“The resulting resynthesized IκBα proteins enter the nucleus and shuttle NF-κB back to the cytoplasm, thereby rapidly repressing NF-κB activatio”
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“The complex p65/p50 is retained in the cytoplasm by the inhibitory protein IkB whose phosphorylation by the IkB kinase (IKK) b component of the IKK signalsome complex leads to its ubiquitylation and proteasomemediated degradation (Ghosh and Karin, 2002).”
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“It is well known that an important pre-requisite for the activation of NF-κB is the phosphorylation and degradation of IκBα, the natural blocker of NF-κB [ 53 ,54].”
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“In most cases, the dose required to suppress NF-kB-dependent reporter activity was similar to that needed for inhibition of NF-kB DNA-binding activity.”
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Metadata
- Authors
- Ghosh, S., & Karin, M.
- Affiliations
- Howard Hughes Medical Institute (US)
- University of California San Diego (US)
- Corresponding author
- Ghosh, Sankar
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2002-04
- Volume
- 109
- Issue
- 2
- Pages
- S81-S96
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W1976382352
- Cited by
- 3,638
- References
- 158
- Citations by year
- 2026: 29 · 2025: 65 · 2024: 66 · 2023: 49 · 2022: 66 · 2021: 94 · 2020: 100 · 2019: 84 · 2018: 103 · 2017: 111 · 2016: 122 · 2015: 141 · 2014: 134 · 2013: 144 · 2012: 189
- FWCI
- 19.54
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- 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
- NF-κB, IκB kinase complex, transcription factor regulation, transcriptional activity, IκB, signal transduction
- MeSH terms
- Animals, Cell Nucleus, Cytoplasm, Enzyme Activation, Gene Expression Regulation, Humans, Signal Transduction, NF-kappa B, Protein Serine-Threonine Kinases, Catalytic Domain, Active Transport, Cell Nucleus, I-kappa B Kinase
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