Identification of poly(ADP-ribose) polymerase as a transcriptional coactivator of the human T-cell leukemia virus type 1 tax protein

Human T-cell leukemia virus type 1 (HTLV-1) encodes a transcriptional activ ator, Tax, whose activity is believed to contribute significantly to cellul ar transformation. Tax stimulates transcription from the proviral promoter as well as from promoters for a variety of cellular genes. The mechanism th rough which Tax communicates to the general transcription factors and RNA p olymerase II has not been completely determined. We investigated whether Ta x could function directly through the general transcription factors and RNA polymerase II or if other intermediary factors or coactivators were requir ed. Our results show that a system consisting of purified recombinant TFIIA , TFIIB, TFIIE, TFIIF, CREB, and Tax, along with highly purified RNA polyme rase II, affinity-purified epitope-tagged TFIID, and semipurified TFIIH, su pports basal transcription of the HTLV-1 promoter but is not responsive to Tax. Two additional activities were required for Tax to stimulate transcrip tion. We demonstrate that one of these activities is poly(ADP-ribose) polym erase (PARP), a:molecule that has been previously identified to be the tran scriptional coactivator PC1. PARP functions as a coactivator in our assays at molar concentrations approximately equal to those of the DNA and equal t o or less than those of the transcription factors in the assay. We further demonstrate that PARP stimulates Tax-activated transcription in vivo, demon strating that this biochemical approach has functionally identified a novel target for the retroviral transcriptional activator Tax.