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 subunit, 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.
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Acknowledgements
The anti-Tax hybridoma was kindly provided by the AIDS Research and Reference Program, NIAID, NIH. This study was supported by Public Health Service grant 2R01 CA68471 to S-C Sun.
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Xiao, G., Sun, SC. Activation of IKKα and IKKβ through their fusion with HTLV-I Tax protein. Oncogene 19, 5198–5203 (2000). https://doi.org/10.1038/sj.onc.1203894
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DOI: https://doi.org/10.1038/sj.onc.1203894
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