In most cells, NF-κB is sequestered in an inactive cytoplasmic form via interactions with the inhibitory proteins IκBα, IκBβ, and IκBε. Cell stimulation induces the release, activation, and nuclear translocation of NF-κB. Release of NF-κB results from the phosphorylation and subsequent proteolytic degradation of the IκB proteins. Two cytokine-inducible IκB kinases (IKKα and IKKβ) phosphorylate and target the IκB proteins for degradation by the ubiquitin pathway. These kinases are components of a 700-900 kDa multisubunit complex that also contains NF-κB/RelA, IκBα, MEKK1, NIK, IKAP, and IKKγ/NEMO (NF-κB essential modulator). IKKγ contains two coiled-coil domains and a leucine zipper which allow it to form dimers and trimers that interact directly with IKKβ. IKKγ, essential for IKKα/IKKβ activation of NF-κB, is located functionally and physically upstream of these subunits. In addition, IKKγ enables the HTLV-1 Tax oncoprotein to interact with IKKβ, resulting in constitutive activation of NF-κB and maintenance of cellular transformation. Thus, IKKγ is an essential element of the IκB complex and an adaptor that mediates stable formation of Tax-IKK complexes.