The Human T-Cell Leukemia Virus Type 1 Tax Protein Confers CBP/p300 Recruitment and Transcriptional Activation Properties to Phosphorylated CREB
The Human T-Cell Leukemia Virus Type 1 Tax Protein Confers CBP/p300 Recruitment and Transcriptional Activation Properties to Phosphorylated CREB
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人类 T 细胞白血病病毒 1 型 Tax 蛋白赋予磷酸化 CREB CBP/p300 募集和转录激活特性
DOI：
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发表时间：
2007
影响因子：
5.3
通讯作者：
J. Nyborg
中科院分区：
文献类型：
--
作者：
Timothy R. Geiger;N. Sharma;Young;J. Nyborg
人类T细胞白血病病毒编码的癌蛋白Tax是一种有效的病毒转录激活因子。Tax功能严格依赖于细胞转录因子CREB，它们一起结合病毒启动子内的cAMP应答元件并介导高水平的病毒转录。信号依赖性CREB在Ser 133（pCREB）的磷酸化与转录的激活相关。这种激活归因于通过与KIX结构域的物理相互作用募集共激活因子CBP/p300。在这里，我们表明，启动子结合税/pCREB复合物强烈招聘重组，纯化全长共激活因子CBP和p300。此外，启动子结合的Tax/pCREB（但不是Tax/CREB）复合物募集天然p300，并有效激活染色质模板的转录。出乎意料的是，单独的pCREB未能可检测地募集全长共激活因子，尽管与KIX有强结合。这些观察结果与已发表的研究结果形成鲜明对比，这些研究表征了KIX和pCREB之间的物理相互作用，并将这些结果外推至全长蛋白质。与我们观察到的pCREB缺乏CBP/p300结合相一致，单独的pCREB不能支持转录激活。这些数据表明CREB的磷酸化不足以进行CBP/p300募集和转录激活。因此，pCREB对转录的调控比通常认识到的更复杂，并且辅调节因子如Tax可能在pCREB功能的调节中起关键作用。
ABSTRACT The human T-cell leukemia virus-encoded oncoprotein Tax is a potent activator of viral transcription. Tax function is strictly dependent upon the cellular transcription factor CREB, and together they bind cAMP response elements within the viral promoter and mediate high-level viral transcription. Signal-dependent CREB phosphorylation at Ser133 (pCREB) correlates with the activation of transcription. This activation has been attributed to recruitment of the coactivators CBP/p300 via physical interaction with the KIX domain. Here we show that the promoter-bound Tax/pCREB complex strongly recruits the recombinant, purified full-length coactivators CBP and p300. Additionally, the promoter-bound Tax/pCREB (but not Tax/CREB) complex recruits native p300 and potently activates transcription from chromatin templates. Unexpectedly, pCREB alone failed to detectably recruit the full-length coactivators, despite strong binding to KIX. These observations are in marked contrast to those in published studies that have characterized the physical interaction between KIX and pCREB and extrapolated these results to the full-length proteins. Consistent with our observation that pCREB is deficient for binding of CBP/p300, pCREB alone failed to support transcriptional activation. These data reveal that phosphorylation of CREB is not sufficient for CBP/p300 recruitment and transcriptional activation. The regulation of transcription by pCREB is therefore more complex than is generally recognized, and coregulators, such as Tax, likely play a critical role in the modulation of pCREB function.
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影响因子：
5.6
作者：
Lenzmeier,BA;Baird,EE;Dervan,PB;Nyborg,JK
通讯作者：
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DOI：
10.1073/pnas.0501076102
发表时间：
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DOI：
10.1073/pnas.88.24.11445
发表时间：
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影响因子：
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作者：
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影响因子：
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