Constitutive activation of NF‐kappa B is essential for transformation of rat fibroblasts by the human T‐cell leukemia virus type I Tax protein

Human T‐cell leukemia virus type I (HTLV‐I) encodes a 40 kDa trans‐acting protein, Tax, that regulates transcription of both the proviral and cellular genes, and can transform rat fibroblasts. To determine the functional importance of its trans‐acting capacities in cell transformation, we have examined two representative pathways of transcriptional activation–HTLV‐I long terminal repeat (LTR) mediated and NF‐kappa B dependent–by mutational analysis of Tax. In contrast to a previous report, mutants lacking the ability to activate an NF‐kappaB‐dependent promoter failed to transform rat fibroblasts, whereas a mutation which abolishes the HTLV‐I LTR‐mediated trans‐activation demonstrated a wild‐type capacity for cell transformation. Stable expression of Tax competent for transformation caused enhanced DNA binding of NF‐kappa B in rat fibroblasts. We also demonstrate that stable co‐expression of the NFKB2 precursor, known as a member of the I kappa B proteins, with wild‐type Tax blocked transformation as well as eliminated aberrant NF‐kappaB activation by Tax without interference with the HTLV‐I LTR‐mediated trans‐activation. Our results indicate that constitutive activation of NF‐kappa B is essential for Tax‐mediated transformation of rat fibroblasts.