Celebrating 25 years of NF-κB research.

Abstract

In the 25 years since its discovery, the nuclear factor-κB (NF-κB) family of transcription factors has been the subject of intensive research in virtually all areas of biomedical science. Research into the function and regulation of this single transcription factor family has been at the forefront of studies in immunology, cancer biology, and molecular pathology, and has progressed hand in hand with conceptual and technological advances in molecular biology, genetic engineering, systems biology, and computational biology. The progress made in elucidating the triggers of NF-κB activation, the components of the NF-κB pathway, and characterization of the physiological and pathophysiological functions of NF-κB have been remarkable. This anniversary therefore represents an excellent opportunity to revisit the work that forms the foundation upon which so much effort and progress has been built. The articles in this volume of Immunological Reviews cover much of what is known about the NF-κB pathway and its basic function. Yet each review also draws attention to the myriad and often surprisingly fundamental issues that remain unresolved. Finally, in marking this important landmark, most reviewers have shared a personal and historical narrative documenting their connection to their area of study in NF-κB. These accounts offer a unique view of the early days of NF-κB research, when so much of the fundamental underpinnings of the pathway were laid down in short order, and provide particular insight into how this field was enriched through the expertise of scientific immigrants from disparate areas of biology, further highlighting the amazing diversity of biological systems influenced by this single transcription factor family. In this introductory article, we lay down some of the most basic and fundamental concepts in order to assist the uninitiated in gaining access to the more detailed discussions that characterize the rest of this issue. Thus, this represents a severely abridged introduction to the NF-κB signaling pathway and its biological function. Where appropriate, we point the reader towards reviews elsewhere in this issue from which they may gain more detailed insight and historical context to the various facets of NF-κB. However, in keeping with the format of this issue, I (S.G.) begin by offering an account of my own involvement with NF-κB.