Cited by 1,693NF-κB Signaling PathwaysSignaling Pathways in DiseaseImmune Response and Inflammation

NF-κB, the first quarter-century: remarkable progress and outstanding questions

Open access
Hayden, Matthew S., Ghosh, Sankar·2012·Genes & Development

Abstract

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.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1101/gad.183434.111

Cites

379 of 379 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • 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].”

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Hayden, M. S., & Ghosh, S.
Affiliations
Columbia University (US)
Venue
Genes & Development
Published
2012-02-01
Volume
26
Issue
3
Pages
203-234
ISSN
  • 0890-9369 (ISSN-L)
  • 1549-5477
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
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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review