Post-translational Control of Intracellular Pathogen Sensing Pathways.
Post-translational Control of Intracellular Pathogen Sensing Pathways.
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DOI：
10.1016/j.it.2016.10.008
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发表时间：
2017-01
影响因子：
16.8
通讯作者：
Gack MU
中科院分区：
文献类型：
--
作者：
Chiang C;Gack MU
哺乳动物细胞通过一组确定的细胞内传感器识别病毒衍生的核酸，包括DNA传感器环GMP-AMP （cGAMP）合成酶（cGAS）和干扰素γ (IFNγ)诱导蛋白16 （IFI16）以及视黄酸诱导基因I （RIG-I）样受体（RLR）家族的病毒RNA受体。在先天免疫识别之后，这些传感器启动一种免疫反应，其特征是许多抗病毒分子的转录上调，包括促炎细胞因子、趋化因子和ifn刺激基因。最近的研究表明，由这些传感器启动的信号转导受到翻译后修饰（PTMs）的复杂调节，导致一个强大但“可调”的细胞因子反应，以维持免疫稳态。在这里，我们总结了ptm和调节酶如何控制RLRs、cGAS和IFI16及其近端接头蛋白的信号活性的最新进展。正前馈调节机制是信号放大的重要手段，保证了先天免疫应答的有效性。然而，负调节回路对于预防过早或过度活跃的促炎反应至关重要，这可能对宿主生物产生有害后果。磷酸化和不同类型的多泛素链，特别是k63连接的泛素化，对于细胞内病毒RNA和DNA受体启动的信号微调是重要的。乙酰化，谷氨酰化和脱酰胺化的先天免疫传感器或组件在其信号通路也动态调节抗病毒细胞因子诱导。对调节先天感知途径的分子机制和调控酶的深入了解可能会导致增强抗病毒免疫或抑制促炎/自身免疫反应的治疗方法。
Mammalian cells recognize virus-derived nucleic acids using a defined set of intracellular sensors including the DNA sensors cyclic GMP–AMP (cGAMP) synthase (cGAS) and interferon gamma (IFNγ)-inducible protein 16 (IFI16) as well as viral RNA receptors of the retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) family. Following innate immune recognition, these sensors launch an immune response that is characterized by the transcriptional upregulation of many antiviral molecules, including proinflammatory cytokines, chemokines, and IFN-stimulated genes. Recent studies have demonstrated that the signal transduction initiated by these sensors is sophisticatedly regulated by post-translational modifications (PTMs) resulting in a robust yet ‘tunable’ cytokine response to maintain immune homeostasis. Here we summarize recent advances in our understanding of how PTMs and regulatory enzymes control the signaling activity of RLRs, cGAS, and IFI16 as well as their proximal adaptor proteins. Positive feedforward regulatory mechanisms serve as an important means of signal amplification to ensure an effective innate immune response. However, negative regulatory circuits are essential for the prevention of premature or overactive proinflammatory responses, which could have harmful consequences for the host organism. Phosphorylation and different types of polyubiquitin chains, particularly K63-linked ubiquitination, are important for fine-tuning signaling initiated by intracellular viral RNA and DNA receptors. Acetylation, glutamylation, and deamidation of innate immune sensors or components in their signaling pathways also dynamically modulate antiviral cytokine induction. Insight into the molecular mechanisms and regulatory enzymes that modulate innate sensing pathways may lead to therapeutics to boost antiviral immunity or dampen proinflammatory/autoimmune responses.
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影响因子：
6.7
作者：
Ansari MA;Dutta S;Veettil MV;Dutta D;Iqbal J;Kumar B;Roy A;Chikoti L;Singh VV;Chandran B
通讯作者：
Chandran B
影响因子：
16
作者：
Inn KS;Gack MU;Tokunaga F;Shi M;Wong LY;Iwai K;Jung JU
通讯作者：
Jung JU
DOI：
10.1083/jcb.201503023
发表时间：
2015-09-14
期刊：
The Journal of cell biology
影响因子：
--
作者：
Kimura T;Jain A;Choi SW;Mandell MA;Schroder K;Johansen T;Deretic V
通讯作者：
Deretic V
影响因子：
7.7
作者：
Friedman, Constantin S.;O'Donnell, Marie Anne;Ting, Adrian T.
通讯作者：
Ting, Adrian T.
RNA 病毒诱导 Siglec-G 通过促进 RIG-I 降解来抑制先天免疫反应
影响因子：
64.5
作者：
Chen, Weilin;Han, Chaofeng;Cao, Xuetao
通讯作者：
Cao, Xuetao