IKK gamma mediates the interaction of cellular I kappa B kinases with the tax transforming protein of human T cell leukemia virus type 1

The Tax oncoprotein of human T cell leukemia virus type 1 constitutively ac tivates transcription factor NF-kappa B by a mechanism involving Tax-induce d phosphorylation of I kappa B alpha, a labile cytoplasmic inhibitor of NF- kappa B. To trigger this signaling cascade, Tax associates stably with and persistently activates a cellular I kappa B kinase (IKK) containing both ca talytic (IKK alpha and IKK beta) and noncatalytic (IKK gamma) subunits. We now demonstrate that IKK gamma enables Tax to dock with the IKK beta cataly tic subunit, resulting in chronic I kappa B kinase activation. Mutations in either IKK gamma or Tax that prevent formation of these higher order Tax.I KK complexes also interfere with the ability of Tax to induce IKK beta cata lytic function in vivo. Deletion mapping studies indicate that amino acids 1-100 of IKK gamma are required for this Tax targeting function. Together, these findings identify IKK gamma as an adaptor protein that directs the st able formation of pathologic Tax.IKK complexes in virally infected T cells.