Article | Published:

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

Nature Immunology volume 9, pages 97104 (2008) | Download Citation

  • A Corrigendum to this article was published on 01 February 2008

This article has been updated

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-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.

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Change history

  • 11 January 2008

    In the version of this article initially published, the bars for the LPS samples in Figure 6b are incorrect. The correct data are presented here.

  • 11 December 2009

    In addition, an incorrect accession code was given for Xenopus laevis Akirin1; the correct code is NP_001089245. These errors have been corrected in the HTML and PDF versions of the article.

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Acknowledgements

We thank S. Stöven for Relish constructs; J.L. Imler for reporter constructs; S. Kurata for support to A.G. and discussions; M. Shiokawa, Y. Fujiwara, L. Troxler, A. Meunier and R. Walther for technical help; M. Hashimoto for secretarial assistance; and our colleagues for discussions and suggestions. Supported by the Japan Society for the Promotion of Science (A.G.), the Centre National de la Recherche Scientifique, the Ministère de l'Education Nationale de la Recherche et de la Technologie, Special Coordination Funds, the Japanese Ministry of Education, Culture, Sports, Science and Technology, the US National Institutes of Health (AI070167 and AI44220) and the Emmy-Noether Program of the Deutsche Forschungsgemeinschaft.

Author information

Author notes

    • Akira Goto

    Present address: Graduate School of Pharmaceutical Sciences, Tohoku University, Aramaki Aoba-ku, Sendai, 980-8578, Japan.

    • Akira Goto
    •  & Kazufumi Matsushita

    These authors contributed equally to this work.

Affiliations

  1. Institut de Biologie Moléculaire et Cellulaire, CNRS UPR 9022, Université Louis Pasteur, 67084 Strasbourg Cedex, France.

    • Akira Goto
    • , Laure El Chamy
    • , Jules A Hoffmann
    •  & Jean-Marc Reichhart
  2. 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.

    • Kazufumi Matsushita
    • , Osamu Takeuchi
    •  & Shizuo Akira
  3. German Cancer Research Center (DKFZ), Boveri-Group Signaling and Functional Genomics, D-69120 Heidelberg, Germany.

    • Viola Gesellchen
    • , David Kuttenkeuler
    •  & Michael Boutros

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Contributions

A.G., V.G., L.E.C. and D.K. did the drosophila experiments. K.M. and O.T. did the mouse experiments. S.A., M.B., O.T. and J.-M.R. conceived and directed the experiments. A.G., O.T., J.A.H. and J.-M.R. wrote the paper. All authors contributed to manuscript criticism.

Corresponding author

Correspondence to Jean-Marc Reichhart.

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    Supplementary Figures 1–6, Table 1 and Methods

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DOI

https://doi.org/10.1038/ni1543

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