PDF(Pubmed)
Abstract：
Signal transduction proteins containing a pLxIS motif induce interferon (IFN) responses central to antiviral immunity. Apart from their established roles in activating the IFN regulator factor (IRF) transcription factors, the existence of additional pathways and functions associated with the pLxIS motif is unknown. Using a synthetic biology-based platform, we identified two orphan pLxIS-containing proteins that stimulate IFN responses independent of all known pattern-recognition receptor pathways. We further uncovered a diversity of pLxIS signaling mechanisms, where the pLxIS motif represents one component of a multi-motif signaling entity, which has variable functions in activating IRF3, the TRAF6 ubiquitin ligase, IκB kinases, mitogen-activated protein kinases, and metabolic activities. The most diverse pLxIS signaling mechanisms were associated with the highest antiviral activities in human cells. The flexibility of domains that regulate IFN signaling may explain their prevalence in nature.
摘要：
含有pLxIS基序的信号转导蛋白诱导对抗病毒免疫至关重要的干扰素(IFN)应答。除了它们在激活IFN调节因子（IRF）转录因子中确立的作用外，与pLxIS基序相关的其他途径和功能的存在尚不清楚。使用基于合成生物学的平台，我们鉴定了两种含有孤儿pLxIS的蛋白质,它们刺激IFN应答,而与所有已知的模式识别受体途径无关.我们进一步发现了pLxIS信号机制的多样性，其中pLxIS基序表示多基序信令实体的一个分量，它在激活IRF3，TRAF6泛素连接酶，IκB激酶,丝裂原活化蛋白激酶,和代谢活动。最多样化的pLxIS信号机制与人细胞中最高的抗病毒活性相关。调节IFN信号传导的结构域的灵活性可以解释它们在本质上的普遍性。
