HTLV-1 TAX ACTIVATION OF THE GM-CSF AND G-CSF PROMOTERS REQUIRES THE INTERACTION OF NF-KB WITH OTHER TRANSCRIPTION FACTOR FAMILIES

The trans-activator protein, tax, from the human T leukemia virus type 1 (HTLV-1) trans-activates both viral and cellular genes. It has prev iously been shown that granulocyte macrophage-colony stimulating facto r (GM-CSF) is constitutively expressed in HTLV-1 infected cells and in cells artificially expressing tax. We show here that the GM-CSF promo ter is tax responsive in fibroblasts and T cells, whereas the granuloc yte (G)-CSF promoter is tax responsive only in fibroblasts. The tax pr otein can activate cellular genes through at least two families of tra nscription factors; the NF-kB/rel and CREB/ATF families. We have used mutant tax proteins to show that the activation of NF-kB proteins is e ssential for tax trans-activation of both the GM-CSF and G-CSF promote rs. The ability of tax to activate CREB/ATF proteins is also essential for GM-CSF trans-activation. We have identified a 44 bp region of the GM-CSF promoter that contains tax responsive elements. This region co ntains a classical NF-kB site, a CK-1 element that can bind the NF-kB p65 protein, as well as a putative ATF binding site. The tax response of the G-CSF promoter requires not only the conserved CK-1 sequence bu t also an adjacent NF-IL6 binding site that may explain the cell restr icted function of the G-CSF promoter.