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Nature:发现能够激发先天免疫系统的分子

来源:Nature 2008-10-03 20:18

美国迈阿密大学的Hiroki Ishikawa 和Glen Barber报告,他们发现了一种名为STING (STimulator of INterferon Genes)的分子,该分子能够识别DNA 和RNA病毒感染,并通过触发干扰素的产生来激发身体的先天免疫系统。

STING(一种以前未定性的蛋白)是在对其激发干扰素β启动子的能力所进行的一项表达筛选(expression screen)研究中分离出来的。它主要存在于内质网中,通过IRF3 和 NF-κB通道的激发来促进干扰素的产生。它还与RIG-I蛋白(一种模式识别受体,参与RNA病毒检测)发生相互作用,也与易位子适配蛋白Sec61β发生相互作用,从而说明易位子或在新生多肽向内质网的内部(cisternal 或lumina)空间转位中所涉及的转位通道在先天免疫信号作用中扮演一定角色。(生物谷Bioon.com)

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Nature 455, 674-678 (2 October 2008) | doi:10.1038/nature07317

STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling

Hiroki Ishikawa & Glen N. Barber

The cellular innate immune system is essential for recognizing pathogen infection and for establishing effective host defence. But critical molecular determinants responsible for facilitating an appropriate immune response—following infection with DNA and RNA viruses, for example—remain to be identified. Here we report the identification, following expression cloning, of a molecule (STING; stimulator of interferon genes) that appears essential for effective innate immune signalling processes. It comprises five putative transmembrane regions, predominantly resides in the endoplasmic reticulum and is able to activate both NF-B and IRF3 transcription pathways to induce expression of type I interferon (IFN- and IFN- ) and exert a potent anti-viral state following expression. In contrast, loss of STING rendered murine embryonic fibroblasts extremely susceptible to negative-stranded virus infection, including vesicular stomatitis virus. Further, STING ablation abrogated the ability of intracellular B-form DNA, as well as members of the herpesvirus family, to induce IFN-, but did not significantly affect the Toll-like receptor (TLR) pathway. Yeast two-hybrid and co-immunoprecipitation studies indicated that STING interacts with RIG-I and with SSR2 (also known as TRAP), which is a member of the translocon-associated protein (TRAP) complex required for protein translocation across the endoplasmic reticulum membrane following translation1, 2. Ablation by RNA interference of both TRAP and translocon adaptor SEC61 was subsequently found to inhibit STING's ability to stimulate expression of IFN-. Thus, as well as identifying a regulator of innate immune signalling, our results imply a potential role for the translocon in innate signalling pathways activated by select viruses as well as intracellular DNA.

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