Kashanchi F, Duvall J F, Kwok R P, Lundblad J R, Goodman R H, Brady J N
Laboratory of Receptor Biology and Gene Expression, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
J Biol Chem. 1998 Dec 18;273(51):34646-52. doi: 10.1074/jbc.273.51.34646.
Tax interacts with the cellular cyclic AMP-responsive element binding protein (CREB) and facilitates the binding of the coactivator CREB binding protein (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) promoter. The trimeric complex is believed to recruit additional regulatory proteins to the HTLV-I long terminal repeat, but there has been no direct evidence that CBP is required for Tax-mediated transactivation. We present evidence that Tax and CBP activate transcription from the HTLV-I 21 base pair 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 the 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 promoter does not involve the stabilization of Tax binding, but rather depends upon gene activation properties of the co-activator that function in the context of a naked DNA template.
Tax与细胞环磷酸腺苷反应元件结合蛋白（CREB）相互作用，并促进共激活因子CREB结合蛋白（CBP）的结合，在人I型嗜T细胞病毒（HTLV-I）启动子中类环磷酸腺苷反应元件（CRE）位点上形成多聚体复合物。据信，三聚体复合物会将其他调控蛋白招募至HTLV-I长末端重复序列，但尚无直接证据表明CBP是Tax介导的反式激活所必需的。我们提供的证据表明，Tax和CBP可激活裸DNA模板上HTLV-I 21碱基对重复序列的转录。HTLV-I序列的转录激活需要Tax和CBP两者，并且可由CBP的N端激活域或全长蛋白介导。荧光偏振结合试验表明，CBP不会显著增强Tax对三聚体复合物的亲和力。转录分析表明，CBP通过促进转录起始和重新起始来激活Tax依赖性转录。CBP激活HTLV-I启动子的能力不涉及Tax结合的稳定，而是取决于在裸DNA模板环境下起作用的共激活因子的基因激活特性。
