The unique role of STAT2 in constitutive and IFN-induced transcription and antiviral responses
The unique role of STAT2 in constitutive and IFN-induced transcription and antiviral responses
复制标题
DOI：
10.1016/j.cytogfr.2016.02.010
复制
发表时间：
2016-06-01
影响因子：
13
通讯作者：
Bluyssen, Hans A. R.
中科院分区：
文献类型：
--
作者：
Blaszczyk, Katarzyna;Nowicka, Hanna;Bluyssen, Hans A. R.
在IFN-I介导的信号传导的经典途径中，STAT 1和STAT 2的磷酸化导致异源二聚化和与IRF 9的相互作用。该复合物也称为IFN-刺激基因因子3（ISGF 3），然后易位到细胞核中并结合IFN-1刺激的应答元件（ISRE），导致超过300种干扰素刺激基因（ISG）的转录激活。此外，形成STAT 1同源二聚体[称为γ-激活因子（GAF）]并易位至细胞核，在那里它们靶向含有γ-激活序列（GAS）的基因ISGF 3的主要功能是通过调节抗病毒ISG的瞬时转录来介导快速和稳健的IFN-1激活应答。这需要ISGF 3从其预先存在的组分STAT 1、STAT 2和IRF 9快速组装并运输到细胞核以结合含ISRE的ISG。活性ISGF 3的形成、核移位和DNA结合中发生的确切事件尚不清楚。多年来，许多研究提供了证据表明存在多种替代的含STAT 2的蛋白。（ISRE或GAS结合）复合物参与IFN-1信号传导，强调了STAT 2在调节特异性IFN-1诱导的转录程序中的重要性，本文综述了STAT 2在非磷酸化和磷酸化ISGF 3组分的差异复合物形成中的独特作用，这些组分直接组成和IFN-I刺激的转录反应。此外，我们强调了STAT 1独立的IFN-I信号通路的存在，其中STAT 2/IRF 9可以潜在地替代ISGF 3的作用，并提供针对病毒感染的后备反应。(C)2016作者爱思唯尔有限公司出版
In the canonical pathway of IFN-I-mediated signaling, phosphorylation of STAT1 and STAT2 leads to heterodimerization and interaction with IRF9. This complex, also known as IFN-stimulated gene factor 3 (ISGF3), then translocates into the nucleus and binds the IFN-I-stimulated response element (ISRE) leading to the activation of transcription of over 300 interferon stimulated genes (ISGs). In addition, STAT1 homodimers [known as gamma-activated factor (GAF)] are formed and translocate to the nucleus, where they target genes containing the,gamma-activated sequence (GAS).The primary function of ISGF3 is to mediate a rapid and robust IFN-I activated response by regulating transient transcription of antiviral ISGs. This requires the quick assembly of ISGF3 from its pre-existing components STAT1, STAT2 and IRF9 and transport to the nucleus to bind ISRE-containing ISGs. The exact events that take place in formation, nuclear translocation and DNA-binding of active ISGF3 are still not clear.Over the years many studies have provided evidence for the existence of a multitude of alternative STAT2-containing (ISRE or GAS-binding) complexes involved in IFN-I signaling, emphasizing the importance of STAT2 in the regulation of specific IFN-I-induced transcriptional programs, independent of its involvement in the classical ISGF3 complex.This review describes the unique role of STAT2 in differential complex formation of unphosphorylated and phosphorylated ISGF3 components that direct constitutive and IFN-I-stimulated transcriptional responses. In addition, we highlight the existence of a STAT1-independent IFN-I signaling pathway, where STAT2/IRF9 can potentially substitute for the role of ISGF3 and offer a back-up response against viral infection. (C) 2016 The Authors. Published by Elsevier Ltd.