DIFFERENTIAL TRANSCRIPTIONAL ACTIVATION BY HUMAN T-CELL LEUKEMIA-VIRUS TYPE-1 TAX MUTANTS IS MEDIATED BY DISTINCT INTERACTIONS WITH CREB BINDING-PROTEIN AND P300

The human T-cell leukemia virus type 1 Tax protein transforms human T lymphocytes, which can lead to the development of adult T-cell leukemi a. Tax transformation is related to its ability to activate gene expre ssion via the ATF/CREB and the NK-kappa B pathways. Transcriptional ac tivation of these pathways is mediated by the actions of the related c oactivators CREB binding protein (CBP) and p300. In this study immunoc ytochemistry and confocal microscopy were used to localize CBP and p30 0 in cells expressing wild-type Tax or Taw mutants that are able to se lectively activate gene expression from either the NF-kappa B or ATF/C REB pathway. Wild-type Tax colocalized with both CBP and p300 in nucle ar bodies which also contained ATF-1 and the RelA subunit of NF-kappa B. However, a Tax mutant that selectively activates gene expression fr om only the ATF/CREB pathway colocalized with CBP bat not p300, while a Tax mutant that selectively activates gene expression from only the NF-kappa B pathway colocalized with p300 but not CBP. In vitro and in vivo protein interaction studies indicated that the integrity of two i ndependent domains of Tax delineated by these mutants was involved in the direct interaction of Tax with either CBP or p300. These studies a re consistent with a model in which activation of either the NF-kappa B or the ATF/CREB pathway bg specific Tax mutants is mediated by disti nct interactions with related coactivator proteins.