PLEIOTROPIC EFFECT OF THE HUMAN T-CELL LEUKEMIA-VIRUS TAX PROTEIN ON THE DNA-BINDING ACTIVITY OF EUKARYOTIC TRANSCRIPTION FACTORS

The Tax protein, encoded by the human T-cell leukemia virus type I, is a potent activator of viral and cellular gene transcription. Tax does not bind DNA directly but appears to trans-activate through an intera ction with host-cell transcription factors that recognize sequences wi thin the promoters of Tax-responsive genes. Cellular transcriptional a ctivators implicated in mediating Tax trans-activation include members of the activating transcription factor/cAMP response element binding protein (ATF/CREB) family of proteins, serum response factor, Fos-Jun, and NF-kappaB. Recent evidence suggests that Tax may stimulate human T-cell leukemia virus type I transcription, at least in part, through enhanced binding of ATF/CREB proteins to their recognition elements wi thin the Tax-responsive 21-bp repeats of the viral promoter. In this r eport, we demonstrate that Tax also enhances the site-specific DNA bin ding activity of serum response factor and Fos-Jun and modestly enhanc es the binding of the NF-kappaB subunits, p50 and p65. We also show th at Tax increases the DNA binding activity of the eukaryotic transcript ion factors ATF-1, Sp1, and GAL4. These results are consistent with th e finding that Tax is highly pleiotropic and suggest that Tax trans-ac tivation may involve enhancement in the DNA binding activity of target transcriptional regulatory proteins. In addition, we show that the me chanism of Tax-enhanced DNA binding activity does not involve an alter ation in the redox state of the target protein.