IKKγ serves as a docking subunit of the IκB kinase (IKK) and mediates interaction of IKK with the human T-cell leukemia virus tax protein

Abstract

The tax gene product of human T-cell leukemia virus type I induces activation of transcription factor NF-κB, which contributes to deregulated expression of various cellular genes. Tax expression triggers persistent phosphorylation and degradation of the NF-κB inhibitory proteins IκBα and IκBα, resulting in constitutive nuclear expression of NF-κB. Recent studies demonstrate that Tax activates the IκB kinase (IKK), although the underlying mechanism remains unclear. In this report, we show that Tax physically interacts with a regulatory component of the IKK complex, the NF- κB essential modulator or IKKγ (NEMO/IKKγ). This molecular interaction appears to be important for recruiting Tax to the IKK catalytic subunits, IKKα and IKKβ. Expression of NEMO/IKKγ greatly promotes binding of Tax to IKKα and IKKβ and stimulates Tax-mediated IKK activation. Interestingly, a mutant form of Tax defective in IKK activation exhibited a markedly diminished level of NEMO/IKKγ association. These findings suggest that the physical interaction of Tax with NEMO/IKKγ may play an important role in Tax-mediated IKK activation.