Akirins are highly conserved nuclear proteins required for NF-kappaB-dependent gene expression in drosophila and mice

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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 Show moreDuring 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. Show less

Nat. Immunol.

journal article

Signal Transduction
Animals
Humans
Mice
Toll-Like Receptors
Immunity
NF-kappa B
Transgenic
Cell Line
Innate
Nuclear Proteins
Proteins
Embryo
Fibroblasts
Interleukin-1beta
Mammalian
Tumor Necrosis Factor-alpha