| Literature DB >> 33406424 |
Hong Sun1, Yu Huang1, Shan Mei1, Fengwen Xu1, Xiaoman Liu1, Fei Zhao1, Lijuan Yin1, Di Zhang1, Liang Wei1, Chao Wu2, Shichao Ma2, Jianwei Wang2, Shan Cen3, Chen Liang4, Siqi Hu5, Fei Guo6.
Abstract
The cyclic GMP-AMP (cGAMP) synthase (cGAS) is a key DNA sensor that initiates STING-dependent signaling to produce type I interferons through synthesizing the secondary messenger 2'3'-cGAMP. In this study, we confirm previous studies showing that cGAS is located both in the cytoplasm and in the nucleus. Nuclear accumulation is observed when leptomycin B is used to block the exportin, CRM1 protein. As a result, leptomycin B impairs the production of interferons in response to DNA stimulation. We further identify a functional nuclear export signal (NES) in cGAS, 169LEKLKL174. Mutating this NES leads to the sequestration of cGAS within the nucleus and the loss of interferon response to cytosolic DNA treatment, and it further determines the key amino acid to L172. Collectively, our data demonstrate that the cytosolic DNA-sensing function of cGAS depends on its presence within the cytoplasm, which is warranted by a functional NES.Entities:
Keywords: DNA sensor; cGAS; innate immune system; nuclear export signal
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Year: 2021 PMID： 33406424 DOI： 10.1016/j.celrep.2020.108586
Source DB: PubMed Journal: Cell Rep Impact factor: 9.423