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NF-κB-dependent Signaling Pathway

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The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
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Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
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Transducer Mechanism: Nuclear Receptors01:31

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Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
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Tumor Necrosis Factor (TNF), a proinflammatory cytokine, contributes significantly to the inflammation seen in Crohn's disease. It exists as soluble TNF and membrane-bound TNF, with actions mediated through TNF receptors (TNFR). TNFR activation leads to the release of proinflammatory cytokines, T-cell activation, collagen production, and leukocyte migration, all contributing to inflammation in Crohn's disease. Anti-TNF monoclonal antibodies, namely infliximab (Remicade), adalimumab...
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The JAK-STAT Signaling Pathway01:20

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Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
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Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
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NF-&#954;B-dependent Luciferase Activation and Quantification of Gene Expression in Salmonella Infected Tissue Culture Cells
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NF-κB and Disease.

Paola Poma1

  • 1Department of Biological, Chemical and Pharmaceutical Science and Technology (STEBICEF), University of Palermo, 90128 Palermo, Italy.

International Journal of Molecular Sciences
|December 5, 2020
PubMed
Summary

Nuclear Factor kappa B (NF-κB) is crucial in inflammatory diseases like cancer and autoimmune conditions. Ongoing research into this transcription factor reveals significant therapeutic potential across diverse conditions.

Area of Science:

  • Molecular Biology
  • Immunology
  • Pathophysiology

Background:

  • The transcription factor Nuclear Factor kappa B (NF-κB) plays a pivotal role in inflammatory processes.
  • Its involvement spans a wide range of diseases, including cancer and autoimmune disorders.

Discussion:

  • Despite extensive knowledge, NF-κB remains a key focus of scientific investigation.
  • Emerging research continues to elucidate its complex functions in disease pathogenesis.

Key Insights:

  • NF-κB's central role in inflammation makes it a critical target for therapeutic intervention.
  • Understanding NF-κB pathways is fundamental to developing novel treatment strategies.

Outlook:

  • Further research into NF-κB signaling pathways holds promise for innovative therapies.

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  • Targeting NF-κB could offer new avenues for managing inflammatory and oncological diseases.