I-B kinase (IKK) is a serine/threonine kinase that phosphorylates I-B␣ and I-B␤ and targets them for polyubiquitination and proteasome-mediated degradation. IKK consists of two highly related catalytic subunits, ␣ and ␤, and a regulatory ␥ subunit, which becomes activated after serine phosphorylation of the activation loops of the catalytic domains. The human T-lymphotropic retrovirus type-I trans-activator, Tax, has been shown to interact directly with IKK␥ and activates IKK via a mechanism not fully understood. Here we demonstrate that IKK binds serine/threonine protein phosphatase 2A (PP2A), and via a tripartite proteinprotein interaction, Tax, IKK␥, and PP2A form a stable ternary complex. In vitro, PP2A down-regulates active IKK prepared from Tax-producing MT4 cells. In the presence of Tax, however, the ability of PP2A to inactivate IKK is diminished. Despite their interaction with IKK␥, PP2A-interaction-defective Tax mutants failed to activate NF-B. Our data support the notion that IKK␥-associated PP2A is responsible for the rapid deactivation of IKK, and inhibition of PP2A by Tax in the context of IKK⅐PP2A⅐Tax ternary complex leads to constitutive IKK and NF-B activation.NF-B/Rel family of transcription factors are controlled by inhibitory I-B proteins I-B␣ and I-B␤ and the I-B-like domains in NF-B1 and NF-B2 that sequester NF-B/Rel in the cytoplasm as multiprotein complexes (for reviews, see Ref.

The unique metabolic profile of PCa allows for many potential avenues of treatment. Future studies will continue to test if the metabolic characterization and treatment of PCa could be an important approach to provide personalized treatment for the disease.