NFBsignaling

NFBsignaling is a cellular signaling pathway that governs transcriptional programs through the activity of the NF-κB family of transcription factors. In many sources, NFBsignaling is used interchangeably with NF-κB signaling, a central regulator of immune and inflammatory responses. The pathway integrates signals from cytokines, microbial products, stress, and other stimuli to control gene expression.

The core components include NF-κB dimers (for example p50/RelA and p52/RelB), the IκB family of inhibitors (IκBα, IκBβ, IκBε), and the IKK complex (comprising IKKα, IKKβ and the regulatory subunit NEMO/IKKγ). In the canonical pathway, activating stimuli lead to phosphorylation of IκB proteins by IKK, marking them for ubiquitination and degradation. This releases NF-κB dimers, which migrate to the nucleus and activate target genes such as cytokines, adhesion molecules and anti-apoptotic proteins. The noncanonical (alternative) pathway relies on processing of the p100 precursor to p52, driven by NIK and IKKα, and controls a subset of genes involved in lymphoid organ development and B-cell maturation.

Regulation includes negative feedback through newly synthesized IκBα, and deactivation by phosphatases and deubiquitinating enzymes. Persistent signaling can contribute to chronic inflammation and cancer. Physiological roles span innate and adaptive immunity, cell proliferation and survival, stress responses, and tissue development.

Therapeutically, NF-κB signaling is a target in inflammatory diseases and cancer. Approaches include inhibitors of IKK, proteasome inhibitors, and modulators of upstream receptors, though clinical use requires balancing anti-inflammatory effects with risks of impaired host defense.