973首席舒红兵半年连发两篇《Cell》子刊

　　

生物通报道，武汉生命科学院特聘教授舒红兵（973首席科学家）抗病毒免疫研究取得进展。继08年9月后舒红兵教授再次在Immunity上发表文章，标题为：The ubiquitin ligase RNF5 regulates antiviral responses by mediating degradation of the adaptor protein MITA，主要解析抗病毒天然免疫的精细调控机制。

 

这是继该研究组08年9月在Immunity发表论文后，半年内在该刊物发表的第二篇研究论文。（08年文章详细点击：http://www.ebiotrade.com/newsf/2008-10/2008107160820.htm），据悉，Immunity杂志自1994年创刊以来，共发表了3篇由我国完成的工作，其中2篇由舒红兵研究组完成。

 

天然免疫是细胞和机体天然存在的非特异性或广谱的抗病原微生物的功能，是机体抵抗病原微生物的第一道防线。抗病毒天然免疫最重要的方式之一是通过I型干扰素（α/β干扰素）来介导的。病毒感染细胞后，诱导细胞产生具有抗病毒功能的I型干扰素。

 

2005年，舒红兵研究组及其它三个实验室各自独立地发现了一个在病毒感染诱导I型干扰素表达的信号传导中不可缺少的蛋白并被分别命名为VISA, MAVS, IPS-1和Cardif。该项成果被认为是细胞抗病毒天然免疫领域中一项路标式的发现及2005年细胞信号传导领域最重要的发现之一。舒红兵研究组的相关论文在Molecular Cell发表后，在3年多的时间里已被SCI他引250多次。2008年9月，舒红兵研究组用表达克隆的方法发现了一个与VISA相互作用、共同定位于线粒体外膜并在病毒感染诱导I型干扰素的信号传导过程中具有关键作用的新接头蛋白MITA，相关论文发表在Immunity，被论文评估机构“Faculty of 1000 Biology”推荐为“必读”论文。

 

在这项最新研究中，舒红兵研究组发现定位于线粒体的E3泛素连接酶RNF5通过泛素化修饰MITA并引起其降解而负调控病毒感染诱导的I型干扰素表达。机体对病毒等的免疫反应如果不被适当的控制，就会引起免疫损伤和疾病。舒红兵研究组的这项最新研究成果为了解抗病毒天然免疫的精细调控机制提供了新线索。

 

生物通推荐原文摘要：The Ubiquitin Ligase RNF5 Regulates Antiviral Responses by Mediating Degradation of the Adaptor Protein MITA

【Summary】

Viral infection activates transcription factors NF-B and IRF3, which collaborate to induce type I interferons (IFNs) and elicit innate antiviral response. MITA (also known as STING) has recently been identified as an adaptor that links virus-sensing receptors to IRF3 activation. Here, we showed that the E3 ubiquitin ligase RNF5 interacted with MITA in a viral-infection-dependent manner. Overexpression of RNF5 inhibited virus-triggered IRF3 activation, IFNB1 expression, and cellular antiviral response, whereas knockdown of RNF5 had opposite effects. RNF5 targeted MITA at Lys150 for ubiquitination and degradation after viral infection. Both MITA and RNF5 were located at the mitochondria and endoplasmic reticulum (ER) and viral infection caused their redistribution to the ER and mitochondria, respectively. We further found that virus-induced ubiquitination and degradation of MITA by RNF5 occurred at the mitochondria. These findings suggest that RNF5 negatively regulates virus-triggered signaling by targeting MITA for ubiquitination and degradation at the mitochondria.

 

舒红兵

武汉大学生命科学院 院长

“****”特聘教授

国家杰出青年基金获得者

 

获奖及荣誉

2006 中国科技部“感染与免疫的基础研究”973项目首席科学家

2005 中国教育部自然科学奖一等奖 (第一完成人)

2004 美国白细胞生物学学会Dolph Adams奖

2001 美国犹太医学及研究中心首届“杰出青年教授奖”

2001 美国Harmon基金会Harmon关节炎研究奖

2000 美国Ellison医学基金会新学者奖

1999 中国国家杰出青年基金获得者

 

代表性论文

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2. Shu, H.B. and Joshi, H.C. (1995). ?-Tubulin can both neacleate microtubule assembly and self-assemble into tubular structures in mammalian cells. J. Cell Biol. 130, 1137-1147.

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5. Shu, H.B., Halpins, D.R. and Goeddel, D.V. (1997). Casper is a FADD and Caspase-related Inducer of Apoptosis. Immunity 6, 751-763.

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11. Wu, M., Xu, L., Li, X., Zhai, Z, and Shu, H.B.* (2002) AMID, an AIF homologous mitochondrion associated protein, inducescaspase-independent apoptosis. J. Biol. Chem. 277:25617-25623.

12. Han, K.J., Su, X., Xu, L.G., Bin, L.H., Zhang, J., Shu, H.B.* (2004) Mechanisms of TRIF-induced ISRE and NF-kappa B activation and apoptosis pathways. J. Biol. Chem. 279:15652-15661.

13. Xu, L.G., Wang, Y.Y., Han, K.J., Li, L.Y., Zhai, Z., Shu, H.B.* (2005) VISA is an adapter protein required for virus-triggered signaling. Molecular Cell 19:727-740

14. Huang, J., Liu, T., Chen, D., Zhai, Z., Shu, H.B.* (2005) SIKE is an IKK-relative kinases-associated suppressor of TLR3- and virus-triggered IRF-3 activation pathways. EMBO Journal 24: 4018-4028

15. Zha, J., Han, K., Xu, L.G., Zhou, Q., Chen, D., Zhai, Z., Shu, H.B.* (2006). The Ret finger protein inhibits signaling mediated by the noncanonical and canonical IKK family members. Journal of Immunology 176: 1072-1080.

 

*通讯作者