The canonical pathway is initiated when ligands such as tumor necrosis factor-alpha (TNF-α) or interleukin-1 (IL-1) bind to their respective receptors. This triggers a cascade of events leading to the phosphorylation and degradation of IκB proteins, which normally inhibit NF-κB by sequestering it in the cytoplasm. Once freed, NF-κB translocates to the nucleus and activates the transcription of target genes.
