IKK gamma serves as a docking subunit of the I kappa B kinase (IKK) and mediates interaction of IKK with the human T-cell leukemia virus Tax protein

The tax gene product of human T-cell leukemia virus type I induces activati on of transcription factor NF-kappa B, which contributes to deregulated exp ression of various cellular genes. Tax expression triggers persistent phosp horylation and degradation of the NF-kappa B inhibitory proteins I kappa B alpha and I kappa B beta resulting in constitutive nuclear expression of NF -KB. Recent studies demonstrate that Tax activates the I kappa B kinase (IK K), although the underlying mechanism remains unclear, In this report, we s how that Tax physically interacts with a regulatory component of the IKK co mplex, the NF-kappa B essential modulator or IKK-gamma (NEMO/IKK gamma). Th is molecular interaction appears to be important for recruiting Tax to the IKK catalytic subunits, IKK alpha and IKK beta. Expression of NEMO/IKK gamm a greatly promotes binding of Tax to IKK alpha and IKK beta and stimulates Tax-mediated IKK activation. Interestingly, a mutant form of Tax defective in IKK activation exhibited a markedly diminished level of NEMO/IKK gamma a ssociation. These findings suggest that the physical interaction of Tax wit h NEMO/IKK gamma may play an important role in Tax-mediated IKK activation.