The IKK Complex, a Central Regulator of NF-kB Activation

The IKK kinase complex is the core element of the NF-kB cascade. It is essentially made of two kinases (IKKa and IKKb) and a regulatory subunit, NEMO/IKKg. Additional components may exist, transiently or permanently, but their characterization is still unsure. In addition, it has been shown that two separate NF-kB pathways exist, depending on the activating signal and the cell type, the canonical (depending on IKKb and NEMO) and the noncanonical pathway (depending solely on IKKa). The main question, which is still only partially answered, is to understand how an NF-kB activating signal leads to the activation of the kinase subunits, allowing them to phosphorylate their targets and eventually induce nuclear translocation of the NF-kB dimers. I will review here the genetic, biochemical, and structural data accumulated during the last 10 yr regarding the function of the three IKK subunits.