生物谷报道：所有的多细胞动物都有一个先天免疫系统：当细菌，寄生虫或真菌侵入肌体，细胞就释放小分子蛋白来清除入侵者。德国癌症研究中心（German Cancer Research Center） 的科学家，现在发现了一种新的分子，它在引发果蝇、小鼠、甚至人类的先天免疫反应中扮演重要的角色。他们的研究结果公布在《自然·免疫学》上。
在表面受体的帮助下，细胞的先天免疫系统能够识别入侵者：一旦这些受体识别外来的物质，他们就会立即将信息通过复杂的信号转导通路传递到细胞内部。细胞接着会释放出免疫活性蛋白。这个信号通路的组分在进化过程中非常地保守，从果蝇到人的各种信号分子，不论是结构还是功能，都十分相似。
以Michael Boutros首的科学家利用RNA干扰（ RNAi）技术，在果蝇中沉默信号转导通路的单个分子，由此发现了一个新成员： Akirin （在日语意思是“搞清楚一个事情”）。当果蝇免疫细胞中Akirin的表达受到抑制，这些细胞就明显较容易受到细菌感染。当他们在所有体细胞敲除该蛋白，果蝇在幼虫的早期即死亡。日本的大阪大学的研究人员在小鼠中研究发现，该蛋白与在果蝇和人类中的作用完全一样。
Michael Boutros说，该信号转导通路中在炎症中发挥着重要作用，而炎症与癌症的发展高度相关。因此，我们要寻找可以抑制这种信号转导通路的小分子物质。第一个抑制其它信号链节点的抑制剂已经进入临床试验阶段。Boutros解释，我们发现的信号链节点越多，我们就越有可能干扰它们。
生物谷推荐原始出处：
Nature Immunology 9, 97 - 104 (2007)
Published online: 9 December 2007 | Corrected online: 11 January 2008 | doi:10.1038/ni1543
Akirins are highly conserved nuclear proteins required for NF-B-dependent gene expression in drosophila and mice
Akira Goto1,4,5, Kazufumi Matsushita2,5, Viola Gesellchen3, Laure El Chamy1, David Kuttenkeuler3, Osamu Takeuchi2, Jules A Hoffmann1, Shizuo Akira2, Michael Boutros3 & Jean-Marc Reichhart1
Abstract
During a genome-wide screen with RNA-mediated interference, we isolated CG8580 as a gene involved in the innate immune response of Drosophila melanogaster. CG8580, which we called Akirin, encoded a protein that acted in parallel with the NF-B transcription factor downstream of the Imd pathway and was required for defense against Gram-negative bacteria. Akirin is highly conserved, and the human genome contains two homologs, one of which was able to rescue the loss-of-function phenotype in drosophila cells. Akirins were strictly localized to the nucleus. Knockout of both Akirin homologs in mice showed that one had an essential function downstream of the Toll-like receptor, tumor necrosis factor and interleukin (IL)-1 signaling pathways leading to the production of IL-6. Thus, Akirin is a conserved nuclear factor required for innate immune responses.
Institut de Biologie Moléculaire et Cellulaire, CNRS UPR 9022, Université Louis Pasteur, 67084 Strasbourg Cedex, France.
Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, ERATO, Japan Science and Technology Agency, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
German Cancer Research Center (DKFZ), Boveri-Group Signaling and Functional Genomics, D-69120 Heidelberg, Germany.
Present address: Graduate School of Pharmaceutical Sciences, Tohoku University, Aramaki Aoba-ku, Sendai, 980-8578, Japan.
These authors contributed equally to this work.
Correspondence to: Jean-Marc Reichhart1 e-mail: jm.reichhart@ibmc.u-strasbg.fr
* In the version of this article initially published, the bars for the LPS samples in Figure 6b are incorrect. The correct data are presented here. The error has been corrected in the HTML and PDF versions of the article.
