NF-κB signal transduction. Extracellular stimulation of microbial ligands such as lipolysaccharide trigger the canonical NF-κB pathway that leads to septic shock. Shortly after stimulation, a series of ubiquitination events occur that activate TAK1 and IKK complexes. This ultimately promotes IκBα phosphorylation and its subsequent proteolysis, thereby allowing the translocation of NF-κB into the nucleus where it promotes the transcription of its target genes. IKK = IκB kinase; JNK = c-Jun N-terminal kinase; MKK6 = Mitogen-activated protein kinase kinase 6; MyD88 = Myeloid differentiation primary response gene (88); NF = nuclear factor; TRAF = TNF-receptor-associated factor.