canonical NF-kappaB signal transduction https://github.com/geneontology/go-ontology/issues/25583 I-kappaB kinase/NF-kappaB cascade I-kappaB kinase/NF-kappaB signal transduction p50-dependent NF-kappaB signaling NF-kappaB cascade I-kappaB kinase/NF-kappaB signaling GO:0007249 Reactome:R-HSA-5357956 An intracellular signaling cassette characterized by the I-kappaB-kinase (IKK)-dependent activation of NF-kappaB, also known as the canonical NF-kappaB signaling cascade. The cascade begins with activation of a trimeric IKK complex (consisting of catalytic kinase subunits IKKalpha and/or IKKbeta, and the regulatory scaffold protein NEMO) and ends with the regulation of transcription of target genes by NF-kappaB. In a resting state, NF-kappaB dimers are bound to I-kappaB proteins, sequestering NF-kappaB in the cytoplasm. Phosphorylation of I-kappaB targets I-kappaB for ubiquitination and proteasomal degradation, thus releasing the NF-kappaB dimers, which can translocate to the nucleus to bind DNA and regulate transcription. The canonical NF-kappaB pathway is mainly stimulated by proinflammatory cytokines such as IL-1beta, tumor necrosis factor (TNF)-alpha, antigen ligands, and toll-like receptors (TLRs). canonical NF-kappaB signaling cascade biological_process Reactome:R-HSA-937072 Reactome:R-HSA-9014325 intracellular signaling cassette