Differential transcriptional activation by human T-cell leukemia virus type 1 Tax mutants is mediated by distinct interactions with CREB binding protein and p300
Differential transcriptional activation by human T-cell leukemia virus type 1 Tax mutants is mediated by distinct interactions with CREB binding protein and p300
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DOI：
10.1128/mcb.18.4.2392
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发表时间：
1998-04-01
影响因子：
5.3
通讯作者：
Gaynor, RB
中科院分区：
文献类型：
--
作者：
Bex, F;Yin, MJ;Gaynor, RB
人类T细胞白血病病毒1型Tax蛋白转化人类T淋巴细胞，可导致成人T细胞白血病的发展。Tax转化与其通过ATF/CREB和NK-κ B途径激活基因表达的能力有关。这些通路的转录激活由相关的共激活因子CREB结合蛋白（CBP）和p300的作用介导。在这项研究中，使用免疫细胞化学和共聚焦显微镜定位CBP和p300在表达野生型Tax或Taw突变体的细胞中，这些突变体能够选择性地激活NF-κ B或ATF/CREB途径的基因表达。野生型Tax与CBP和p300共定位于核小体中，核小体还含有ATF-1和NF-κ B的RelA亚基。然而，选择性激活仅来自ATF/CREB途径的基因表达的Tax突变体与CBP共定位而不是p300，而选择性激活仅来自NF-κ B途径的基因表达的Tax突变体与p300共定位而不是CBP。在体外和体内蛋白质相互作用的研究表明，完整的两个独立的结构域的税收划定这些突变体参与的直接相互作用的税收与CBP或p300。这些研究与NF-κ B或ATF/CREB B途径bg特异性Tax突变体的激活通过与相关共激活蛋白的不同相互作用介导的模型一致。
The human T-cell leukemia virus type 1 Tax protein transforms human T lymphocytes, which can lead to the development of adult T-cell leukemia. Tax transformation is related to its ability to activate gene expression via the ATF/CREB and the NK-kappa B pathways. Transcriptional activation of these pathways is mediated by the actions of the related coactivators CREB binding protein (CBP) and p300. In this study immunocytochemistry and confocal microscopy were used to localize CBP and p300 in cells expressing wild-type Tax or Taw mutants that are able to selectively activate gene expression from either the NF-kappa B or ATF/CREB pathway. Wild-type Tax colocalized with both CBP and p300 in nuclear bodies which also contained ATF-1 and the RelA subunit of NF-kappa B. However, a Tax mutant that selectively activates gene expression from only the ATF/CREB pathway colocalized with CBP bat not p300, while a Tax mutant that selectively activates gene expression from only the NF-kappa B pathway colocalized with p300 but not CBP. In vitro and in vivo protein interaction studies indicated that the integrity of two independent domains of Tax delineated by these mutants was involved in the direct interaction of Tax with either CBP or p300. These studies are consistent with a model in which activation of either the NF-kappa B or the ATF/CREB pathway bg specific Tax mutants is mediated by distinct interactions with related coactivator proteins.