The coactivator CBP stimulates human T-cell lymphotrophic virus type I Taxtransactivation in vitro

Tax interacts with the cellular cyclic AMP-responsive element binding prote in (CREB) and facilitates the binding of the coactivator CREB binding prote in (CBP), forming a multimeric complex on the cyclic AMP-responsive element (CRE)-like sites in the human T-cell lymphotrophic virus type I (HTLV-I) p romoter. The trimeric complex is believed to recruit additional regulatory proteins to the HTLV-I long terminal repeat, but there has been no direct e vidence that CBP is required for Tax-mediated transactivation. We present e vidence that Tax and CBP activate transcription from the HTLV-I 21 base pai r repeats on naked DNA templates. Transcriptional activation of the HTLV-I sequences required both Tax and CBP and could be mediated, by either the N- terminal activation domain of CBP or the full-length protein. Fluorescence polarization binding assays indicated that CBP does not markedly enhance th e affinity of Tax for the trimeric complex. Transcription analyses suggest that CBP activates Tax-dependent transcription by promoting transcriptional initiation and reinitiation. The ability of CBP to activate the HTLV-I pro moter does not involve the stabilization of Tax binding, but rather depends upon gene activation properties of the co-activator that function in the c ontext of a naked DNA template.