The NF-κ B-independent functions of IKK subunits in immunity and cancer

The IKK complex is involved in transcriptional activation by phosphorylating the inhibitory molecule IkBa, a modification that triggers its subsequent degradation, allowing activation of NF-kB. Importantly, recent reports indicate that multiple cytoplasmic and nuclear proteins distinct from the NF-kB/IkB proteins are phosphorylated by the catalytic subunits of the IKK complex, IKKa or IKKb. Here we describe how the IKK subunits can play crucial roles in allergy, inflammation, immunity by targeting proteins such as SNAP23 and IRF7 but also in cancer by phosphorylating key molecules such as p53, TSC1 and FOXO3a through NF-kB-independent pathways. Thus, these recent findings considerably widen the biological roles played by these kinases and suggest that a full understanding of the biological roles played by IKKa and IKKb requires an exhaustive characterization of their substrates.