College of Pharmacy, The Catholic University of Korea, 43, Jibong-Ro, Wonmi-Gu, Bucheon-Si, Gyeonggi-Do, 14662, Republic of Korea.
College of Biological Sciences, University of Minnesota, 3-104 MCB, 420, Washington Ave, SE, Minneapolis, MN, 55455, USA.
Exp Mol Med. 2020 Sep;52(9):1526-1536. doi: 10.1038/s12276-020-00506-6. Epub 2020 Sep 25.
Signal transducer and activator of transcription (STAT2) is a member of the STAT family that plays an essential role in immune responses to extracellular and intracellular stimuli, including inflammatory reactions, invasion of foreign materials, and cancer initiation. Although the majority of STAT2 studies in the last few decades have focused on interferon (IFN)-α/β (IFNα/β) signaling pathway-mediated host defense against viral infections, recent studies have revealed that STAT2 also plays an important role in human cancer development. Notably, strategic research on STAT2 function has provided evidence that transient regulatory activity by homo- or heterodimerization induces its nuclear localization where it to forms a ternary IFN-stimulated gene factor 3 (ISGF3) complex, which is composed of STAT1 and/or STAT2 and IFN regulatory factor 9 (IEF9). The molecular mechanisms of ISGF3-mediated ISG gene expression provide the basic foundation for the regulation of STAT2 protein activity but not protein quality control. Recently, previously unknown molecular mechanisms of STAT2-mediated cell proliferation via STAT2 protein quality control were elucidated. In this review, we briefly summarize the role of STAT2 in immune responses and carcinogenesis with respect to the molecular mechanisms of STAT2 stability regulation via the proteasomal degradation pathway.
信号转导子和转录激活子 (STAT2) 是 STAT 家族的成员之一，在细胞外和细胞内刺激的免疫反应中发挥着重要作用，包括炎症反应、外来物质的入侵和癌症的发生。尽管过去几十年中大多数关于 STAT2 的研究都集中在干扰素 (IFN)-α/β (IFNα/β) 信号通路介导的宿主抗病毒感染防御上，但最近的研究表明 STAT2 也在人类癌症发展中发挥着重要作用。值得注意的是，对 STAT2 功能的策略性研究提供了证据，证明同二聚体或异二聚体的瞬时调节活性诱导其核定位，在核内形成一个三元干扰素刺激基因因子 3 (ISGF3) 复合物，由 STAT1 和/或 STAT2 和干扰素调节因子 9 (IEF9) 组成。ISGF3 介导的 ISG 基因表达的分子机制为 STAT2 蛋白活性的调节但不是蛋白质量控制提供了基本基础。最近，通过蛋白体降解途径阐明了 STAT2 介导的细胞增殖的 STAT2 蛋白质量控制的先前未知的分子机制。在这篇综述中，我们简要总结了 STAT2 在免疫反应和癌变中的作用，以及通过蛋白酶体降解途径调节 STAT2 稳定性的分子机制。
