Caspase-Dependent Cleavage of DDX21 Suppresses Host Innate Immunity.
Caspase-Dependent Cleavage of DDX21 Suppresses Host Innate Immunity.
复制标题
DDX21 的 Caspase 依赖性裂解抑制宿主先天免疫
作者：
Wu W;Qu Y;Yu S;Wang S;Yin Y;Liu Q;Meng C;Liao Y;Ur Rehman Z;Tan L;Song C;Qiu X;Liu W;Ding C;Sun Y
DEAD（Glu-Asp-Ala-Glu）盒RNA解旋酶已被证明有助于抗病毒先天免疫。DDX 21 RNA解旋酶被鉴定为参与rRNA加工和RNA解旋的核蛋白。DDX 21也被证明是DDX 1-DDX 21-DHX 36复合物中的支架蛋白，其感测双链RNA并启动下游先天免疫。在这里，我们确定DDX 21在病毒感染和用RNA/DNA配体处理后经历半胱天冬酶依赖性切割，特别是对于RNA病毒和配体。胱天蛋白酶-3/6在D126处切割DDX 21并促进其响应于病毒感染从细胞核易位到细胞质。胞质裂解的DDX 21通过抑制DDX 1-DDX 21-DHX 36复合物的形成来负调节干扰素β（IFN-β）信号传导途径。因此，我们的数据将DDX 21鉴定为免疫平衡的调节剂，最重要的是揭示了DDX 21切割在对病毒的先天免疫应答中的潜在作用。
DEAD (Glu-Asp-Ala-Glu) box RNA helicases have been proven to contribute to antiviral innate immunity. The DDX21 RNA helicase was identified as a nuclear protein involved in rRNA processing and RNA unwinding. DDX21 was also proven to be the scaffold protein in the complex of DDX1-DDX21-DHX36, which senses double-strand RNA and initiates downstream innate immunity. Here, we identified that DDX21 undergoes caspase-dependent cleavage after virus infection and treatment with RNA/DNA ligands, especially for RNA virus and ligands. Caspase-3/6 cleaves DDX21 at D126 and promotes its translocation from the nucleus to the cytoplasm in response to virus infection. The cytoplasmic cleaved DDX21 negatively regulates the interferon beta (IFN-β) signaling pathway by suppressing the formation of the DDX1-DDX21-DHX36 complex. Thus, our data identify DDX21 as a regulator of immune balance and most importantly uncover a potential role of DDX21 cleavage in the innate immune response to virus.