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-kappa B. Here we show that Tax triggers activation of cellular protein kinases, I kappa B kinase alpha (IKK alpha) and IKK beta, which phosphorylate the NF-kappa B inhibitory protein I kappa B alpha, resulting in its degradation and NF-kappa B 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-kappa B signaling also requires the NF-kappa B-inducing kinase (NIK). Consistently, inactive forms of either IKKs or NIK. attenuate Tax-mediated NF-kappa B activation. Therefore, Tax activates NF-kappa B by targeting cellular signaling molecules, including both IKKs and NIK.