美國邁阿密大學(xué)的Hiroki Ishikawa 和Glen Barber報告,，他們發(fā)現(xiàn)了一種名為STING (STimulator of INterferon Genes)的分子,，該分子能夠識別DNA 和RNA病毒感染,，并通過觸發(fā)干擾素的產(chǎn)生來激發(fā)身體的先天免疫系統(tǒng),。
STING（一種以前未定性的蛋白）是在對其激發(fā)干擾素β啟動子的能力所進(jìn)行的一項表達(dá)篩選（expression screen）研究中分離出來的,。它主要存在于內(nèi)質(zhì)網(wǎng)中,，通過IRF3 和 NF-κB通道的激發(fā)來促進(jìn)干擾素的產(chǎn)生,。它還與RIG-I蛋白（一種模式識別受體，參與RNA病毒檢測）發(fā)生相互作用,，也與易位子適配蛋白Sec61β發(fā)生相互作用,，從而說明易位子或在新生多肽向內(nèi)質(zhì)網(wǎng)的內(nèi)部（cisternal 或lumina）空間轉(zhuǎn)位中所涉及的轉(zhuǎn)位通道在先天免疫信號作用中扮演一定角色。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
