NF-κB-inducing Kinase and IκB Kinase Participate in Human T-cell Leukemia Virus I Tax-mediated NF-κB Activation

• DOI: 10.1074/jbc.273.33.21132
• Publication Date: 2002-07-26T15:02:22Z
• Authors: Mark Uhlik; LiFeng Good; Gutian Xiao; Edward W. Harhaj; Ebrahim Zandi; Michael Karin; Shao-Cong Sun
• Keywords: 0301 basic medicine; Jurkat Cells; 03 medical and health sciences; NF-kappa B; NF-kappaB-Inducing Kinase; Humans; Gene Products, tax; Phosphorylation; Protein Serine-Threonine Kinases; Catalysis; I-kappa B Kinase; 3. Good health

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