Goto Akira, Matsushita Kazufumi, Gesellchen Viola, El Chamy Laure, Kuttenkeuler David, Takeuchi Osamu, Hoffmann Jules A, Akira Shizuo, Boutros Michael, Reichhart Jean-Marc
Institut de Biologie Moléculaire et Cellulaire, CNRS UPR 9022, Université Louis Pasteur, 67084 Strasbourg Cedex, France.
Nat Immunol. 2008 Jan;9(1):97-104. doi: 10.1038/ni1543. Epub 2007 Dec 9.
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-kappaB 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)-1beta signaling pathways leading to the production of IL-6. Thus, Akirin is a conserved nuclear factor required for innate immune responses.
在一项利用RNA介导的干扰进行的全基因组筛选中，我们分离出CG8580基因，它参与黑腹果蝇的固有免疫反应。我们将CG8580命名为Akirin，它编码一种蛋白，该蛋白在Imd途径下游与核因子κB转录因子协同发挥作用，是抵御革兰氏阴性菌所必需的。Akirin高度保守，人类基因组包含两个同源物，其中一个能够挽救果蝇细胞中的功能缺失表型。Akirin严格定位于细胞核。敲除小鼠的两个Akirin同源物表明，其中一个在Toll样受体、肿瘤坏死因子和白细胞介素（IL）-1β信号通路下游具有导致IL-6产生的重要功能。因此，Akirin是固有免疫反应所需的一种保守核因子。
