Delving into the complexities of inflammation and immunity! This review explores the intricate role of NF-κB, a transcription factor central to immune responses, inflammation, and cell growth. It focuses on its regulation by IκB proteins and the diverse stimuli that activate NF-κB, highlighting recent advances in understanding its mechanisms. The review examines how NF-κB activation is controlled by targeted phosphorylation and degradation of IκB, enabling NF-κB to enter the nucleus and activate gene transcription. It also discusses the discovery of multiple IκB forms, which appear to regulate NF-κB through different mechanisms, and recent structural and gene knockout studies that provide new insights into NF-κB function. Furthermore, the review examines the potential therapeutic targets. These discoveries hold promise for developing targeted therapies for diseases involving inappropriate NF-κB activation, such as inflammatory disorders and certain cancers. By elucidating the regulatory mechanisms governing NF-κB, this review contributes to the development of novel therapeutic strategies.
As a review in the Annual Review of Immunology, this article synthesizes current knowledge on NF-κB and IκB proteins, core components of the immune system. It aligns with the journal's focus on providing comprehensive and critical assessments of key topics in immunology, offering a valuable resource for researchers in the field.