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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Drosophila Proteins / biosynthesis*
  • Drosophila Proteins / genetics
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism*
  • Embryo, Mammalian / cytology
  • Fibroblasts / metabolism
  • Humans
  • Immunity, Innate
  • Interleukin-1beta / immunology
  • Mice
  • Mice, Transgenic
  • NF-kappa B / biosynthesis*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / physiology*
  • Proteins / genetics
  • Proteins / physiology*
  • Signal Transduction
  • Toll-Like Receptors / immunology
  • Tumor Necrosis Factor-alpha / immunology


  • Akirin1 protein, mouse
  • Drosophila Proteins
  • Interleukin-1beta
  • NF-kappa B
  • Nuclear Proteins
  • Proteins
  • Toll-Like Receptors
  • Tumor Necrosis Factor-alpha