Finding NEMO mutations

A wide variety of inflammatory stimuli trigger the activation of IκB kinase (IKK), the enzyme complex that activates the NF-κB transcription factors. But all NF-κB–inducing signals are not the same, according to Filipe-Santos and colleagues (page 1745), who identify mutations in the regulatory subunit of IKK that selectively disarm just one of these pathways.

Most NF-κB–inducing stimuli, including byproducts of microbial infection and inflammatory cytokines, trigger the phosphorylation of the α and β subunits of IKK. Heterodimers of IKKα and β then bind to IKKγ (or NEMO)—the regulatory subunit of the complex. Thus assembled, this protein complex phosphorylates the NF-κB inhibitor proteins (IκBs), tagging it for proteasomal degradation and freeing NF-κB for translocation into the nucleus.

Here, Filipe-Santos et al. identify two point mutations in NEMO in patients with an X-linked susceptibility to...