HTLV-I tax protein binds to MEKK1 to stimulate IκB kinase activity and NF-κB activation

NF-kappa B, a key regulator of the cellular inflammatory and immune response, is activated by the HTLV-I transforming and transactivating protein Tax. We show that Tax binds to the amino terminus of the protein kinase MEKK1, a component of an I kappa B kinase complex, and stimulates MEKK1 kinase activity. Tax expression increases the activity of I kappa B kinase 8 (IKK beta) to enhance phosphorylation of serine residues in I kappa B alpha that lead to its degradation. Dominant negative mutants of both IKK beta and MEKK1 prevent Tax activation of the NF-kappa B pathway. Furthermore, recombinant MEKK1 stimulates IKK beta phosphorylation of I kappa B alpha. Thus, Tax-mediated increases in NF-kappa B nuclear translocation result from direct interactions of Tax and MEKK1 leading to enhanced IKK beta phosphorylation of I kappa B alpha.