activation. Specifically, mutations at the ATP-binding site or in the kinase activation loop can create dominant-negative IKKα and IKKβ, which are capable of blocking NF-κB activation [39–43]. Because of their distinct roles in the canonical and non-canonical NF-κB activation pathways, dominant-negative IKK mutants’ can show stimulus-dependent inhibition [44]. Adenoviral-mediated delivery of an IKKβ dominant-negative kinase has been shown to have therapeutic potential for airway inflammatory diseases such as asthma [45, 46]. NEMO can also serve as a target for inhibiting the IKK complex. In particular, introducing a cell-permeable 10 amino-acid peptide that corresponds to the NEMO-binding domain of IKKβ can block the binding of NEMO to IKK in response to TNF in the canonical pathway [47].
