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

By M. Hayden, S. Ghosh. Genes & Development, 2012

1,748 citations recorded by the source corpus.

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.

Subfields: Cancer Research, Immunology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/2145038707917ec865a3e4eefb235b207369b500

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Citations in the corpus

Transcriptional Regulation and its Misregulation in Disease (2013, positive): “NF-kB is found in most cell types and is involved in cellular responses to stimuli such as infection and stress (Hayden and Ghosh, 2012).”
CD4⁺ follicular helper T cell infiltration predicts breast cancer survival. (2013, neutral): “promoting Th1, Th17, and Treg responses (46).”
Inflammatory responses and inflammation-associated diseases in organs (2015, background): “IκB phosphorylation results in its degradation by the proteasome and the subsequent release of NF-κB for nuclear translocation and gene transcription activation [30].”
30 years of NF-κB: a blossoming of relevance to human pathobiology (2017, positive): “We know now that there is specificity information all around the target genes, from which other transcription factors may be bound along with NF-κB, to the specific binding site sequence and its effect on the detailed structure of NF-κB, to the particular form of NF-κB that best binds to a particula”
The complexity of NF-κB signaling in inflammation and cancer (2013, background): “As a consequence, dimers of p50 and p52, which bind to NF-κB elements of gene promoters, act as transcriptional repressors [6].”
Mesenchymal Differentiation Mediated by NF-κB Promotes Radiation Resistance in Glioblastoma (2013, background): “For example, NF-kB promotes an inflammatory response through secretion of TNF-a, IL-1b, and IL-6, of which IL-6 triggers STAT3 activation (Ben-Neriah and Karin, 2011; Hayden and Ghosh, 2012).”
Fusobacterium nucleatum potentiates intestinal tumorigenesis and modulates the tumor immune microenvironment (2013, background): “The expression signature, notable for PTGS2 (COX-2), IL1β, IL6, IL8, TNF (TNF- α) and MMP3, was suggestive of an NF-κB-driven pro-inflammatory response (Hayden et al., 2012 and http://www.bu.edu/nf-kb/gene-resources/target-genes/).”
The Regulation of NF-κB Subunits by Phosphorylation (2016, background): “Both precursors also contain C-terminal ankyrin repeats, which confer IκB-like function by sequestering interacting NF-κB subunits in the cytoplasm [2].”