Activation of IKK alpha and IKK beta through their fusion with HTLV-I Tax protein

Human T-cell leukemia virus type I (HTLV-I) Tax protein persistently stimul ates the activity of I kappaB kinase (IKK), resulting in constitutive activ ation of the transcription factor NF-kappaB. Tax activation of IKK requires physical interaction of this viral protein with the IKK regulatory subunit , IKK gamma. The Tax/IKK gamma interaction allows Tax to engage the IKK cat alytic subunits, IKK alpha and IKK beta, although it remains unclear whethe r this linker function of IKK gamma is sufficient for supporting the Tax-sp ecific IKK activation. To address this question, we have examined the seque nces of IKK gamma required for modulating the Tax/IKK signaling. We demonst rate that when fused to Tax, a small N-terminal fragment of IKK gamma, cont aining its minimal IKK alpha/beta -binding domain, is sufficient for bringi ng Tax to and activating the IKK catalytic subunits, Disruption of the IKK alpha/beta -binding activity of this domain abolishes its function in modul ating the Tax/IKK signaling. We further demonstrate that direct fusion of T ax to IKK alpha and IKK beta leads to activation of these kinases. These fi ndings suggest that the IKK gamma -directed Tax/TKK association serves as a molecular trigger for IKK activation.