The human T-cell leukemia virus type-1 Tax protein regulates the activity of the I kappa B kinase complex

Two cytokine-inducible kinases, IKK alpha and IKK beta, are components of a 700-kDa kinase complex that specifically phosphorylates I kappa B. Phospho rylation of I kappa B by IKK leads to its ubiquitination and subsequent deg radation, resulting in the nuclear translocation of NF-kappa B. The oncogen ic protein Tax, encoded by human T-cell leukemia virus type-1 (HTLV-1), sti mulates IKK activity to result in constitutive nuclear levels of NF-kappa B . In an attempt to gain insights into the mechanism by which Tax mediates c onstitutive activation of the NF-kappa B pathway, we analyzed the chromatog raphic distribution of IKK proteins using cellular extracts prepared from t hree T lymphocytes either lacking or containing Tax. IKK kinase activity an d the distribution of proteins in the IKK complex were characterized, In ex tracts prepared from cells containing Tax, the activity of both IKK alpha a nd IKK beta present in the 700-kDa IKK complex were increased. Surprisingly , cell lines expressing Tax also contained an additional peak of IKK beta, but not IKK alpha activity, that migrated at 300 kDa rather than at 700 kDa , We noted that extracts containing Tax had extremely low levels of I kappa B beta, but not I kappa B alpha, and contained predominantly a truncated f orm of the MAP3K MEKK1. These results suggest that Tax may target several c omponents of the NF-kappa B pathway leading to constitutive activation of t his important regulator of cellular gene expression.