NF-κB, the first quarter-century: remarkable progress and outstanding questions
Open accessAbstract
The ability to sense and adjust to the environment is crucial to life. For multicellular organisms, the ability to respond to external changes is essential not only for survival but also for normal development and physiology. Although signaling events can directly modify cellular function, typically signaling acts to alter transcriptional responses to generate both transient and sustained changes. Rapid, but transient, changes in gene expression are mediated by inducible transcription factors such as NF-κB. For the past 25 years, NF-κB has served as a paradigm for inducible transcription factors and has provided numerous insights into how signaling events influence gene expression and physiology. Since its discovery as a regulator of expression of the κ light chain gene in B cells, research on NF-κB continues to yield new insights into fundamental cellular processes. Advances in understanding the mechanisms that regulate NF-κB have been accompanied by progress in elucidating the biological significance of this transcription factor in various physiological processes. NF-κB likely plays the most prominent role in the development and function of the immune system and, not surprisingly, when dysregulated, contributes to the pathophysiology of inflammatory disease. As our appreciation of the fundamental role of inflammation in disease pathogenesis has increased, so too has the importance of NF-κB as a key regulatory molecule gained progressively greater significance. However, despite the tremendous progress that has been made in understanding the regulation of NF-κB, there is much that remains to be understood. In this review, we highlight both the progress that has been made and the fundamental questions that remain unanswered after 25 years of study.
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The production of SASP inflammatory factors is primarily driven by NF-κB.
“The production of SASP inflammatory factors is primarily driven by NF-κB, a rapid-acting transcription factor that orchestrates the response to a range of cellular stressors (33).”
From Connecting aging biology and inflammation in the omics era (2022) · cites this paper as [33]
NF-κB is a family of transcription factors (p50, p52, p65, RelB, c-Rel) that translocate to the nucleus in response to stimuli.
“After demonstrating the ability to screen genetic knockouts for optical phenotypes, we sought to identify genes required for activation of NF-κB, a family of transcription factors (p50, p52, p65, RelB and c-Rel) that translocate to the nucleus in response to a host of stimuli (Gewurz et al., 2012; Hayden and Ghosh, 2012; Pahl, 1999).”
From Optical Pooled Screens in Human Cells (2019) · cites this paper as Hayden and Ghosh, 2012
NF-KB is expressed in all cell types, is involved in the oxidative stress mechanism by expression of numerous genes such as cytokines, and plays a major role in the pathology of inflammatory disease.
“NF-kappB (NF-KB) has been studied for more than 25 years and is known to be expressed in all cell types, where it is involved in the oxidative stress mechanism by the expression of numerous genes, such as the cytokines, and plays a major role in the pathology of inflammatory disease [104,105].”
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“Nuclear localization of the p50/p65 NF-κB dimer enables transcriptional activation of this complex so we analyzed p65 nuclear accumulation as a readout of NF-κB localization (Hayden and Ghosh, 2012).”
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- Authors
- Hayden, M. S., & Ghosh, S.
- Affiliations
- Columbia University (US)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2012-02-01
- Volume
- 26
- Issue
- 3
- Pages
- 203-234
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC3278889
- OpenAlex
- W2138934663
- Cited by
- 1,693
- References
- 379
- Citations by year
- 2026: 89 · 2025: 83 · 2024: 117 · 2023: 88 · 2022: 104 · 2021: 109 · 2020: 123 · 2019: 130 · 2018: 142 · 2017: 125 · 2016: 146 · 2015: 144 · 2014: 121 · 2013: 131 · 2012: 40
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases (R01AI068977, AI093985, R01AI093985, R37AI033443, AI033443, R01AI033443, AI068977)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (P30AR058886)
- 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, inducible transcription factors, gene expression regulation, signal transduction, immune system development, inflammation, inflammatory diseases, B cells, kappa light chain genes, transcriptional regulation
- MeSH terms
- Animals, Enzyme Activation, Gene Expression Regulation, Humans, Immune System, Signal Transduction, NF-kappa B
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