Article abstract
Nature Immunology 9, 97 - 104 (2008)
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
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