Activation of IKKα and IKKβ through their fusion with HTLV-I Tax protein

Human T-cell leukemia virus type I (HTLV-I) Tax protein persistently stimulates the activity of I kappaB kinase (IKK), resulting in constitutive activation 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 catalytic subunits, IKK alpha and IKK beta, although it remains unclear whether this linker function of IKK gamma is sufficient for supporting the Tax-specific IKK activation. To address this question, we have examined the sequences of IKK gamma required for modulating the Tax/IKK signaling. We demonstrate that when fused to Tax, a small N-terminal fragment of IKK gamma, containing its minimal IKK alpha/beta -binding domain, is sufficient for bringing Tax to and activating the IKK catalytic subunits, Disruption of the IKK alpha/beta -binding activity of this domain abolishes its function in modulating the Tax/IKK signaling. We further demonstrate that direct fusion of Tax to IKK alpha and IKK beta leads to activation of these kinases. These findings suggest that the IKK gamma -directed Tax/TKK association serves as a molecular trigger for IKK activation.