NF-κB-inducing kinase and IκB kinase participate in human T-cell leukemia virus I tax-mediated NF-κB activation

The tax gene product of human T-cell leukemia virus I induces aberrant expression of various cellular genes, which contributes to transformation of host cells. Induction of many Tax target genes is mediated through transcription factor NF-κB. Here we show that Tax triggers activation of cellular protein kinases, IκB kinase α (IKKα) and IKKβ, which phosphorylate the NF-κB inhibitory protein IκBα, resulting in its degradation and NF-κB activation. Constitutive IKK activation occurs in both Tax-transfected and human T-cell leukemia virus I-infected T cells. We further demonstrate that Tax-mediated NF-κB signaling also requires the NF- κB-inducing kinase (NIK). Consistently, inactive forms of either IKKs or NIK attenuate Tax-mediated NF-κB activation. Therefore, Tax activates NF-κB by targeting cellular signaling molecules, including both IKKs and NIK.