Transcriptional activity of interferon regulatory factor (IRF)-3 depends on multiple protein-protein interactions.
Transcriptional activity of interferon regulatory factor (IRF)-3 depends on multiple protein-protein interactions.
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干扰素调节因子 (IRF)-3 的转录活性取决于多种蛋白质-蛋白质相互作用。
DOI：
10.1046/j.1432-1033.2002.03330.x
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
Wathelet,MarcG
中科院分区：
文献类型：
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作者：
Yang,Hongmei;Lin,CharlesH;Ma,Gang;Orr,Melissa;Baffi,MichaelO;Wathelet,MarcG
病毒感染导致参与宿主抗病毒防御的一组细胞基因的激活。IRF-3已被确定为该过程中的关键转录因子。IRF-3的活化机制尚未完全阐明，但它涉及由其C末端的病毒依赖性磷酸化引发的构象变化。这种构象变化导致核积累、DNA结合和转录反式激活。在这里，我们发现IRF-3的两组不同的Ser/Thr残基在磷酸化时在功能上协同作用以实现最大激活。值得注意的是，我们发现激活的IRF-3缺乏转录活性，但完全通过募集p300/CBP共激活因子来激活转录。此外，我们发现IRF-3的两个独立结构域与p300/CBP的几个不同区域相互作用。干扰这些相互作用中的任何一种都会导致转录活性的完全丧失，这表明二价相互作用对于IRF-3募集辅激活因子至关重要。
Virus infection results in the activation of a set of cellular genes involved in host antiviral defense. IRF‐3 has been identified as a critical transcription factor in this process. The activation mechanism of IRF‐3 is not fully elucidated, yet it involves a conformational change triggered by the virus‐dependent phosphorylation of its C‐terminus. This conformational change leads to nuclear accumulation, DNA binding and transcriptional transactivation. Here we show that two distinct sets of Ser/Thr residues of IRF‐3, on phosphorylation, synergize functionally to achieve maximal activation. Remarkably, we find that activated IRF‐3 lacks transcriptional activity, but activates transcription entirely through the recruitment of the p300/CBP coactivators. Moreover, we show that two separate domains of IRF‐3 interact with several distinct regions of p300/CBP. Interference with any of these interactions leads to a complete loss of transcriptional activity, suggesting that a bivalent interaction is essential for coactivator recruitment by IRF‐3.