Figure 3.

Activation of innate immune signaling pathway by lipopolysaccharide (LPS) and tumor necrosis factor (TNF). LPS is bound by toll-like receptor 4 (TLR4), and then adaptor protein MyD88 interacts with IRAK protein kinases. Recruitment of IRAK complex results in association with another adaptor protein, TRAF6, and this leads to IκB kinase (IKK) activation. NF-κB is a functional transcription factor after IκBα phosphorylation and subsequent dissociation of the complex of NF-κB and IκBα. IκBα, an inhibitor of NF-κB, can also be degraded by way of ubiquitination. Ubiquitinated IκB is degraded in proteasome and NF-κB moves to the nucleus, where it activates the proinflammatory cytokine transcription. A different way of activating the NF-κB pathway shown here is through binding of TNF by TNF receptor 1 (TNFR1). Adaptor protein TRADD recruits receptor-binding protein 1 (RIP1) and TNFR-associated factor TRAF2. RIP1 activates IKK complex and thus also NF-κB pathway. It is shown that A20 and otulin interact with Ub chains in the signaling pathway.