Abstract
Human T-cell leukemia virus type I (HTLV-I) Tax protein persistently stimulates the activity of IκB kinase (IKK), resulting in constitutive activation of the transcription factor NF-κB. Tax activation of IKK requires physical interaction of this viral protein with the IKK regulatory suhunit, IKKγ. The Tax/IKKγ interaction allows Tax to engage the IKK catalytic subunits, IKKα and IKKβ, although it remains unclear whether this linker function of IKKγ is sufficient for supporting the Tax-specific IKK activation. To address this question, we have examined the sequences of IKKγ required for modulating the Tax/IKK signaling. We demonstrate that when fused to Tax, a small N-terminal fragment of IKKγ, containing its minimal IKKα/β-binding domain, is sufficient for bringing Tax to and activating the IKK catalytic subunits. Disruption of the IKKα/β-binding activity of this domain abolishes its function in modulating the Tax/IKK signaling. We further demonstrate that direct fusion of Tax to IKKα and IKKβ leads to activation of these kinases. These findings suggest that the IKKγ-directed Tax/IKK association serves as a molecular trigger for IKK activation.
Original language | English (US) |
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Pages (from-to) | 5198-5203 |
Number of pages | 6 |
Journal | Oncogene |
Volume | 19 |
Issue number | 45 |
DOIs | |
State | Published - Oct 26 2000 |
Keywords
- HTLV-I Tax
- IκB kinase
- NF-κB
- T-cell activation
ASJC Scopus subject areas
- Molecular Biology
- Genetics
- Cancer Research