CONSTITUTIVE PHOSPHORYLATION AND TURNOVER OF I-KAPPA-B-ALPHA IN HUMANT-CELL LEUKEMIA-VIRUS TYPE I-INFECTED AND TAX-EXPRESSING T-CELLS

Human T-cell leukemia virus type I (HTLV-I) encodes a strong transcrip tional activator, Tax, that stimulates transcription indirectly throug h the viral long terminal repeat and also activates a number of cellul ar genes via association with host transcription factors. The NF-kappa B/Rel pathway is a target for Tax trans-activation, and Tax has been correlated with increased NF-kappa B-binding activity and NF-kappa B-d ependent gene expression in HTLV-I-infected cells. In this study we de monstrate that constitutive phosphorylation and increased turnover of the regulatory I kappa B alpha protein in HTLV-I-infected MT-2 and C81 66 cells and Tax-expressing 19D cells contribute to constitutive NF-ka ppa B-bindidg activity, which consists primarily of c-Rel, p52(NFKB2), and p50(NFKB1). I kappa B alpha mRNA expression is also increased 7- to 20-fold in these cells, although the steady-state level of I kappa B alpha protein is reduced in HTLV-I-infected and Tax-expressing T cel ls. These results indicate that the viral Tax protein, by indirectly m ediating phosphorylation of I kappa B, may target I kappa B alpha for rapid degradation, thus leading to constitutive NF-kappa B activity.