Akirins are highly conserved nuclear proteins required for NF-kappaB-dependent gene expression in drosophila and mice.
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.
Goto
Akira
A
Institut de Biologie Moléculaire et Cellulaire, CNRS UPR 9022, Université Louis Pasteur, 67084 Strasbourg Cedex, France.
Matsushita
Kazufumi
K
Gesellchen
Viola
V
El Chamy
Laure
L
Kuttenkeuler
David
D
Takeuchi
Osamu
O
Hoffmann
Jules A
JA
Akira
Shizuo
S
Boutros
Michael
M
Reichhart
Jean-Marc
JM
D000818:Animals; D002460:Cell Line; D029721:Drosophila Proteins / Q000096:biosynthesis* / Q000235:genetics; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000166:cytology; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D053583:Interleukin-1beta / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000096:biosynthesis*; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
C559424:Akirin1 protein, mouse; D029721:Drosophila Proteins; D053583:Interleukin-1beta; D016328:NF-kappa B; D009687:Nuclear Proteins; D011506:Proteins; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha