NF-KB Canonical

The NF-kB family of transcription factors plays important roles in the immune system. Two signaling pathways lead to the activation of NF-kB, known as the classical (canonical) pathway and the non-canonical (alternative) pathway. The common regulatory step is activation of an IkB kinase (IKK) complex consisting of catalytic kinase subunits (IKKalpha and/or IKKbeta) and the regulatory non-enzymatic scaffold protein NEMO (NF-kB essential modulator also known as IKKgamma). Activation of NF-kB dimers is due to IKK-mediated phosphorylation-induced proteasomal degradation of IkB, enabling the active NF-kB transcription factor subunits to translocate to the nucleus and induce target gene expression. The canonical NF-kB pathway is induced by several signals including antigens, TLR ligands and cytokines such as TNF. It uses a wide variety of signaling adaptors to engage and activate the IKKbeta subunit of the IKK complex. IKKbeta phosphorylation of classical IkB proteins bound to NF-kB dimers such as p50-p65 results in ubiquitination (Ub) of IkB and proteasome-induced degradation.