生物谷報(bào)道：所有的多細(xì)胞動(dòng)物都有一個(gè)先天免疫系統(tǒng)：當(dāng)細(xì)菌，寄生蟲或真菌侵入肌體,，細(xì)胞就釋放小分子蛋白來清除入侵者,。德國癌癥研究中心（German Cancer Research Center） 的科學(xué)家,，現(xiàn)在發(fā)現(xiàn)了一種新的分子，它在引發(fā)果蠅,、小鼠,、甚至人類的先天免疫反應(yīng)中扮演重要的角色。他們的研究結(jié)果公布在《自然·免疫學(xué)》上。
在表面受體的幫助下，細(xì)胞的先天免疫系統(tǒng)能夠識(shí)別入侵者：一旦這些受體識(shí)別外來的物質(zhì),，他們就會(huì)立即將信息通過復(fù)雜的信號(hào)轉(zhuǎn)導(dǎo)通路傳遞到細(xì)胞內(nèi)部,。細(xì)胞接著會(huì)釋放出免疫活性蛋白。這個(gè)信號(hào)通路的組分在進(jìn)化過程中非常地保守,，從果蠅到人的各種信號(hào)分子,，不論是結(jié)構(gòu)還是功能，都十分相似,。
以Michael Boutros首的科學(xué)家利用RNA干擾（ RNAi）技術(shù),，在果蠅中沉默信號(hào)轉(zhuǎn)導(dǎo)通路的單個(gè)分子，由此發(fā)現(xiàn)了一個(gè)新成員： Akirin （在日語意思是“搞清楚一個(gè)事情”）,。當(dāng)果蠅免疫細(xì)胞中Akirin的表達(dá)受到抑制,，這些細(xì)胞就明顯較容易受到細(xì)菌感染。當(dāng)他們在所有體細(xì)胞敲除該蛋白,，果蠅在幼蟲的早期即死亡,。日本的大阪大學(xué)的研究人員在小鼠中研究發(fā)現(xiàn)，該蛋白與在果蠅和人類中的作用完全一樣,。
Michael Boutros說,，該信號(hào)轉(zhuǎn)導(dǎo)通路中在炎癥中發(fā)揮著重要作用，而炎癥與癌癥的發(fā)展高度相關(guān),。因此,，我們要尋找可以抑制這種信號(hào)轉(zhuǎn)導(dǎo)通路的小分子物質(zhì),。第一個(gè)抑制其它信號(hào)鏈節(jié)點(diǎn)的抑制劑已經(jīng)進(jìn)入臨床試驗(yàn)階段。Boutros解釋,，我們發(fā)現(xiàn)的信號(hào)鏈節(jié)點(diǎn)越多,，我們就越有可能干擾它們。
生物谷推薦原始出處：
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: [email protected]
* 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.
