Figure 2.

The formation of M1-Ub chains and their interaction with NEMO are required for TAK1 to initiate the activation of the canonical IKK complex. (a) IL-1 α induces the formation of M1-Ub chains in embryonic fibroblasts from wild-type (WT) mice, but not in knock-in mice expressing the E3 ligase-inactive HOIP[C879S] mutant. (b) The IL-1α-dependent, TAK1-catalysed phosphorylation of IKKβ at Ser177 is suppressed in embryonic fibroblasts from HOIP[C879S] knock-in mice that do not form M1-Ub chains, or in embryonic fibroblasts from NEMO[D311N] knock-in mice in which M1-Ub chains are formed, but are unable to interact with NEMO. Adapted from Emmerich et al.³⁶ and Zhang et al.³⁷