Nuclear factorKB (NFKB) can be activated by a multitude of different stimuli, like TNFA, LPS and CD40L

Nuclear factor-κB (NF-κB) can be activated by a multitude of different stimuli, like TNFα, LPS and CD40L. Activation of the canonical (also known as classical) pathway via Toll-like receptor (TLR) or cytokine receptor signaling depends on the IKK complex, which is composed of the kinases IKKα and IKKβ, and the regulatory subunit IKKγ (NEMO). Activated IKK phosphorylates (P) IκBα to induce its degradation by the 26S proteasome, allowing NF-κB dimers (p50-p65) to translocate to the nucleus and bind to DNA to induce NF-κB target gene transcription. Activation of the non-canonical (also known as alternative) pathway is strictly dependent on IKKα homodimers. The target for IKKα homodimers is NF-κB2/p100, which upon activation of IKKα by NIK is phosphorylated and incompletely degraded into p52, resulting in the release and nuclear translocation of p52-RelB dimers. This pathway can be triggered by the activation of members of the TNF-receptor superfamily such as CD40 (that also induce canonical NF-κB signaling), but not via pattern recognition receptors such as TLRs.

Publication

Gene Therapy Targeting Nuclear Factor-κB: Towards Clinical Application in Inflammatory Diseases and Cancer. (2009) Sander W. Tas, et al. Curr Gene Ther. 2009 Jun;9(3):160-170. Figure: F1. All organisms Rattus norvegicus Canis lupus familiaris Oryctolagus cuniculus Homo sapiens Mus musculus Danio rerio

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