Inhibition of IL-1beta transcription by peptides derived from the hCMV IE2 transactivator.
Inhibition of IL-1beta transcription by peptides derived from the hCMV IE2 transactivator.
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DOI：
10.1016/j.molimm.2007.12.024
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发表时间：
2008-05
影响因子：
3.6
通讯作者：
J. Listman;J. E. Race;N. Walker-Kopp;Sebnem Unlu;P. Auron
中科院分区：
文献类型：
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作者：
J. Listman;J. E. Race;N. Walker-Kopp;Sebnem Unlu;P. Auron
人巨细胞病毒(HCMV)的即刻早期(IE)蛋白在病毒和宿主细胞转录中具有不同的作用。其中之一是IE2诱导单核细胞中编码IL-1β的IL1B基因转录的能力。IE2与宿主细胞转录因子SPI-1/PU.1(SPI-1)之间的相互作用部分解释了这一功能。我们现在发现，最大的IE2功能还取决于定位于IL1B启动子上的两个C/eBP位点的生产性相互作用，这表明IE2、Spi-1和C/eBPβ之间在启动子上的两个不同位置存在双分子或三分子相互作用。Spi-1上的IE2相互作用区先前被定位到与DNA结合的Ets结构域，并与转录因子C/EBPβ相互作用的Spi-1区域重叠，转录因子C/EBP是一个已知在诱导IL1B应答Toll/IL-1受体(TIR)家族信号转导中起关键作用的因子。IE2的Spi-1相互作用区映射到氨基酸315-328，该序列也与C/EBPβ的bZIP结构域相互作用。编码IE2 291-364氨基酸的表达载体可抑制共转IL 1B增强子-启动子片段的单核细胞内毒素诱导。这种抑制可能是Spi-1和C/EBPβ竞争的结果，从而钝化了基因诱导。
The immediate early (IE) proteins of human cytomegalovirus (hCMV) have diverse roles in directing viral and host cell transcription. Among these is the ability of IE2 to induce transcription of the IL1B gene that codes for IL-1β in monocytes. This function is partially explained by interaction between IE2 and the host cell transcription factor Spi-1/PU.1 (Spi-1). We now show that maximal IE2 function also depends on productive interactions localizing to two C/EBP sites on the IL1B promoter suggesting either bi- or tri-molecular interactions between IE2, Spi-1 and C/EBPβ at two different locations on the promoter. The IE2 interaction region on Spi-1 was previously mapped to the DNA-binding ETS domain and overlaps the region of Spi-1 that interacts with the transcription factor C/EBPβ, a factor known to be critical for the induction of IL1B in response to Toll/IL-1 receptor (TIR) family signal transduction. The Spi-1 interacting region of IE2 maps to amino acids 315–328, a sequence that also interacts with the bZIP domain of C/EBPβ. An expression vector coding for amino acids 291–364 of IE2 can suppress LPS induction of a co-transfected IL1B enhancer–promoter fragment in a monocyte cell line. This inhibition is likely the result of competition between Spi-1 and C/EBPβ, thus blunting gene induction.