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Nature Immunology 9, 97–104 (1 January 2008) | doi:10.1038/ni1543

Akirins are highly conserved nuclear proteins required for NF-|[kappa]|B-dependent gene expression in drosophila and mice

Akira Goto , Kazufumi Matsushita , Viola Gesellchen , Laure El Chamy , David Kuttenkeuler , Osamu Takeuchi , Jules A Hoffmann , Shizuo Akira , Michael Boutros & Jean-Marc Reichhart

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-κB 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)-1β signaling pathways leading to the production of IL-6. Thus, Akirin is a conserved nuclear factor required for innate immune responses.