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首页> 外文期刊>Nature immunology >Different modes of ubiquitination of the adaptor TRAF3 selectively activate the expression of type I interferons and proinflammatory cytokines.
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Different modes of ubiquitination of the adaptor TRAF3 selectively activate the expression of type I interferons and proinflammatory cytokines.

机译:衔接子TRAF3的泛素化的不同模式选择性激活I型干扰素和促炎细胞因子的表达。

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摘要

Balanced production of type I interferons and proinflammatory cytokines after engagement of Toll-like receptors (TLRs), which signal through adaptors containing a Toll-interleukin 1 receptor (TIR) domain, such as MyD88 and TRIF, has been proposed to control the pathogenesis of autoimmune disease and tumor responses to inflammation. Here we show that TRAF3, a ubiquitin ligase that interacts with both MyD88 and TRIF, regulated the production of interferon and proinflammatory cytokines in different ways. Degradative ubiquitination of TRAF3 during MyD88-dependent TLR signaling was essential for the activation of mitogen-activated protein kinases (MAPKs) and production of inflammatory cytokines. In contrast, TRIF-dependent signaling triggered noncanonical TRAF3 self-ubiquitination that activated the interferon response. Inhibition of degradative ubiquitination of TRAF3 prevented the expression of all proinflammatory cytokines without affecting the interferon response.
机译:已经提出,Toll样受体(TLR)参与后I型干扰素和促炎性细胞因子的平衡产生是通过控制包含Toll-白介素1受体(TIR)域的衔接子(例如MyD88和TRIF)发出的,以控制I型干扰素和促炎细胞因子的发病。自身免疫性疾病和肿瘤对炎症的反应。在这里,我们显示TRAF3,一种与MyD88和TRIF相互作用的泛素连接酶,以不同的方式调节干扰素和促炎细胞因子的产生。 MyD88依赖的TLR信号转导期间,TRAF3的降解泛素化对于激活有丝分裂原激活的蛋白激酶(MAPK)和产生炎性细胞因子至关重要。相反,TRIF依赖性信号触发了非典型的TRAF3自遍在蛋白化,从而激活了干扰素的应答。抑制TRAF3的降解泛素化可阻止所有促炎细胞因子的表达,而不会影响干扰素的应答。

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