SLC19A1 Is an Importer of the Immunotransmitter cGAMP.,Molecular Cell

当前位置： X-MOL 学术 › Mol. Cell › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

SLC19A1 Is an Importer of the Immunotransmitter cGAMP.
Molecular Cell ( IF 14.5 ) Pub Date : 2019-05-21 , DOI: 10.1016/j.molcel.2019.05.006
Christopher Ritchie ₁ , Anthony F Cordova ₁ , Gaelen T Hess ₂ , Michael C Bassik ₂ , Lingyin Li ₁

Affiliation

2'3'-cyclic-GMP-AMP (cGAMP) is a second messenger that activates the antiviral stimulator of interferon genes (STING) pathway. We recently identified a novel role for cGAMP as a soluble, extracellular immunotransmitter that is produced and secreted by cancer cells. Secreted cGAMP is then sensed by host cells, eliciting an antitumoral immune response. Due to the antitumoral effects of cGAMP, other CDN-based STING agonists are currently under investigation in clinical trials for metastatic solid tumors. However, it is unknown how cGAMP and other CDNs cross the cell membrane to activate intracellular STING. Using a genome-wide CRISPR screen, we identified SLC19A1 as the first known importer of cGAMP and other CDNs, including the investigational new drug 2'3'-bisphosphosphothioate-cyclic-di-AMP (2'3'-CDAS). These discoveries will provide insight into cGAMP's role as an immunotransmitter and aid in the development of more targeted CDN-based cancer therapeutics.

中文翻译：

SLC19A1 是免疫递质 cGAMP 的导入蛋白。

2'3'-环状-GMP-AMP (cGAMP) 是激活干扰素基因抗病毒刺激剂 (STING) 途径的第二信使。我们最近发现了 cGAMP 作为一种由癌细胞产生和分泌的可溶性细胞外免疫递质的新作用。然后分泌的 cGAMP 被宿主细胞感知，引发抗肿瘤免疫反应。由于 cGAMP 的抗肿瘤作用，其他基于 CDN 的 STING 激动剂目前正在针对转移性实体瘤的临床试验中进行研究。然而，cGAMP 和其他 CDN 如何穿过细胞膜激活细胞内 STING 尚不清楚。通过全基因组 CRISPR 筛选，我们确定 SLC19A1 是第一个已知的 cGAMP 和其他 CDN 的导入者，包括研究中的新药 2'3'-二磷酸硫代磷酸酯-环-二-AMP (2'3'-CDAS)。这些发现将深入了解 cGAMP 作为免疫递质的作用，并有助于开发更有针对性的基于 CDN 的癌症疗法。

更新日期：2019-05-21

点击分享查看原文

点击收藏

公开下载

阅读更多本刊新发论文本刊介绍/投稿指南