Circuitry of nuclear factor kappaB signaling

Immunol Rev. 2006 Apr;210:171-86. doi: 10.1111/j.0105-2896.2006.00375.x.


Over the past few years, the transcription factor nuclear factor (NF)-kappaB and the proteins that regulate it have emerged as a signaling system of pre-eminent importance in human physiology and in an increasing number of pathologies. While NF-kappaB is present in all differentiated cell types, its discovery and early characterization were rooted in understanding B-cell biology. Significant research efforts over two decades have yielded a large body of literature devoted to understanding NF-kappaB's functioning in the immune system. NF-kappaB has been found to play roles in many different compartments of the immune system during differentiation of immune cells and development of lymphoid organs and during immune activation. NF-kappaB is the nuclear effector of signaling pathways emanating from many receptors, including those of the inflammatory tumor necrosis factor and Toll-like receptor superfamilies. With this review, we hope to provide historical context and summarize the diverse physiological functions of NF-kappaB in the immune system before focusing on recent advances in elucidating the molecular mechanisms that mediate cell type-specific and stimulus-specific functions of this pleiotropic signaling system. Understanding the genetic regulatory circuitry of NF-kappaB functionalities involves system-wide measurements, biophysical studies, and computational modeling.

Publication types

  • Review

MeSH terms

  • Humans
  • Immune System / physiology*
  • Immunity, Innate / genetics*
  • NF-kappa B / chemistry
  • NF-kappa B / metabolism
  • NF-kappa B / physiology*
  • Protein Conformation
  • Signal Transduction


  • NF-kappa B