Scheme 1.

Simplified scheme illustrating how NEMO mediates the phosphorylation of IκB by IKKα/β in response to activation of an upstream receptor (in this example, TNFR1), leading to ubiquitination and degradation of IκB, releasing NF-κB to translocate to the nucleus where it stimulates expression of target genes. Abbreviations: TNF, tumor necrosis factor; TNFR1, p55 TNF receptor; TRAF6, TNF receptor associated factor 6; RIP, receptor-interacting serine/threonine-protein kinase 1; TAK1, TGF β activated kinase 1, a.k.a. mitogen-activated protein kinase kinase kinase 7; p50/p65, a dimer comprising one form of the transcription factor NF-κB; IκB, inhibitor of κB; NEMO, NF-κB essential modulator; IKKα/β, inhibitor of κB kinase α and β; Ub, ubiquitin. The red asterisks represent sites of phosphorylation.