STAT2 is an essential adaptor in USP18-mediated suppression of type I interferon signaling.
STAT2 is an essential adaptor in USP18-mediated suppression of type I interferon signaling.
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DOI：
10.1038/nsmb.3378
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发表时间：
2017-03
影响因子：
16.8
通讯作者：
Zhang DE
中科院分区：
文献类型：
--
作者：
Arimoto KI;Löchte S;Stoner SA;Burkart C;Zhang Y;Miyauchi S;Wilmes S;Fan JB;Heinisch JJ;Li Z;Yan M;Pellegrini S;Colland F;Piehler J;Zhang DE
Type I interferons (IFNs) are multifunctional cytokines that regulate immune responses and cellular functions but also can have detrimental effects on human health. A tight regulatory network therefore controls IFN signaling, which in turn interferes with medical interventions. The JAK-STAT signaling pathway transmits the IFN extracellular signal to the nucleus for alterations of gene expression. STAT2 is a well-known essential and specific positive effector of type I IFN signaling. Here, we report that STAT2 is also a previously unrecognized crucial component of the USP18-mediated negative feedback control in both, human and murine cells. We found that STAT2 recruits USP18 to the type I IFN receptor subunit IFNAR2 via its constitutive membrane-distal STAT2 binding site. This mechanistic coupling of effector and negative feedback functions of STAT2 provides novel strategies in treatment of IFN signaling related human diseases.
