Circuitry of nuclear factor kappaB signaling.
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.
Hoffmann
Alexander
A
Signaling Systems Laboratory, Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA. ahoffmann@ucsd.edu
Baltimore
David
D
D006801:Humans; D007107:Immune System / Q000502:physiology*; D007113:Immunity, Innate / Q000235:genetics*; D016328:NF-kappa B / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D011487:Protein Conformation; D015398:Signal Transduction
D016328:NF-kappa B